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A Study Evaluating the of OPC-34712 in Subjects With Normal Hepatic Function and Hepatically Impaired Subjects

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ClinicalTrials.gov Identifier: NCT01299454
Recruitment Status : Completed
First Posted : February 18, 2011
Results First Posted : September 3, 2015
Last Update Posted : October 20, 2015
Sponsor:
Information provided by (Responsible Party):
Otsuka Pharmaceutical Development & Commercialization, Inc.

Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition: Schizophrenia
Intervention: Drug: OPC-34712

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
81 participants were screened; of these 45 participants were enrolled recruited at 3 study sites in the United States (US).

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Mild Hepatic Impairment Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 milligrams (mg).
Moderate Hepatic Impairment Participants with moderate hepatic impairment (Child-Pugh classification scheme)received a single dose of oral brexpiprazole 2 mg.
Severe Hepatic Impairment Participants with severe hepatic impairment (based on Child-Pugh classification scheme) received a single dose of oral brexpiprazole 2 mg.
Normal Hepatic Function Participants with normal hepatic function (based on Child-Pugh classification scheme) received a single dose of oral brexpiprazole 2 mg.

Participant Flow:   Overall Study
    Mild Hepatic Impairment   Moderate Hepatic Impairment   Severe Hepatic Impairment   Normal Hepatic Function
STARTED   8   8   6   23 
COMPLETED   8   8   6   23 
NOT COMPLETED   0   0   0   0 



  Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Mild Hepatic Impairment Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Moderate Hepatic Impairment Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Severe Hepatic Impairment Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Participants with normal hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Total Total of all reporting groups

Baseline Measures
   Mild Hepatic Impairment   Moderate Hepatic Impairment   Severe Hepatic Impairment   Normal Hepatic Function   Total 
Overall Participants Analyzed 
[Units: Participants]
 8   8   6   23   45 
Age 
[Units: Years]
Mean (Standard Deviation)
 59.5  (7.3)   57.8  (3.8)   51.2  (4.4)   56.2  (5.2)   56.4  (5.7) 
Gender 
[Units: Participants]
         
Female   3   2   0   5   10 
Male   5   6   6   18   35 


  Outcome Measures

1.  Primary:   Unbound Brexpiprazole Area Under the Concentration Time Curve (AUC) Calculated to the Last Observable Concentration at Time t (AUCt,u)   [ Time Frame: Day 1 to Day 8 ]

Measure Type Primary
Measure Title Unbound Brexpiprazole Area Under the Concentration Time Curve (AUC) Calculated to the Last Observable Concentration at Time t (AUCt,u)
Measure Description Blood samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose/Early termination (ET).
Time Frame Day 1 to Day 8  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Pharmacokinetics (PK) set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations.

Reporting Groups
  Description
Mild Hepatic Impairment Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Matched to Mild Hepatic Function

Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg.

Each participant with normal hepatic function was matched to a participant with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.

Moderate Hepatic Impairment Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Matched to Moderate Hepatic Function.

Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg.

Each participant with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.

Severe Hepatic Impairment Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Matched to Severe Hepatic Function.

Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg.

Each participant with normal hepatic function was matched to a participant with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.


Measured Values
   Mild Hepatic Impairment   Normal Hepatic Function Matched to Mild Hepatic Function   Moderate Hepatic Impairment   Normal Hepatic Function Matched to Moderate Hepatic Function.   Severe Hepatic Impairment   Normal Hepatic Function Matched to Severe Hepatic Function. 
Participants Analyzed   8   8   8   8   6   6 
Unbound Brexpiprazole Area Under the Concentration Time Curve (AUC) Calculated to the Last Observable Concentration at Time t (AUCt,u) 
[Units: nanograms.hours/mL (ng*h/mL)]
Mean (Standard Deviation)
 5.95  (2.58)   4.87  (1.78)   5.41  (1.37)   4.28  (1.95)   3.27  (0.93)   3.63  (1.54) 


Statistical Analysis 1 for Unbound Brexpiprazole Area Under the Concentration Time Curve (AUC) Calculated to the Last Observable Concentration at Time t (AUCt,u)
Groups [1] Mild Hepatic Impairment vs. Normal Hepatic Function Matched to Mild Hepatic Function
Statistical Test Type [2] Non-Inferiority or Equivalence
Statistical Method [3] Mixed effect analysis of variance
Geometric Mean Ratio [4] 1.166
90% Confidence Interval 0.776 to 1.751
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The primary comparison was each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the primary PK parameters between each hepatic disease group and the control group, the 90% confidence interval (CI) for the difference in the means of the log-transformed data was calculated using a mixed effect analysis of variance.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normal-theory CIs, this approach was equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Other relevant estimation information:
  Due to the nature of the normal-theory CIs, this approach is equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance.

Statistical Analysis 2 for Unbound Brexpiprazole Area Under the Concentration Time Curve (AUC) Calculated to the Last Observable Concentration at Time t (AUCt,u)
Groups [1] Moderate Hepatic Impairment vs. Normal Hepatic Function Matched to Moderate Hepatic Function.
Statistical Test Type [2] Non-Inferiority or Equivalence
Statistical Method [3] Mixed effect analysis of variance
Geometric Mean Ratio [4] 1.375
90% Confidence Interval 0.915 to 2.066
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The primary comparison was each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the primary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the log-transformed data was calculated using a mixed effect analysis of variance.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normal-theory CIs, this approach was equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Other relevant estimation information:
  Due to the nature of the normal-theory CIs, this approach is equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance.

Statistical Analysis 3 for Unbound Brexpiprazole Area Under the Concentration Time Curve (AUC) Calculated to the Last Observable Concentration at Time t (AUCt,u)
Groups [1] Severe Hepatic Impairment vs. Normal Hepatic Function Matched to Severe Hepatic Function.
Statistical Test Type [2] Non-Inferiority or Equivalence
Statistical Method [3] Mixed effect analysis of variance
Geometric Mean Ratio [4] 0.929
90% Confidence Interval 0.581 to 1.488
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The primary comparison was each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the primary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the log-transformed data was calculated using a mixed effect analysis of variance.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normal-theory CIs, this approach was equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Other relevant estimation information:
  Due to the nature of the normal-theory CIs, this approach is equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance.



2.  Primary:   Unbound Brexpiprazole AUC Calculated From Time Zero to Infinity (AUC∞,u)   [ Time Frame: Day 1 to Day 8 ]

Measure Type Primary
Measure Title Unbound Brexpiprazole AUC Calculated From Time Zero to Infinity (AUC∞,u)
Measure Description

Blood samples were taken at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose/ET.

AUC (0 - ∞)= AUC from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞).

Time Frame Day 1 to Day 8  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations.

Reporting Groups
  Description
Mild Hepatic Impairment Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg
Normal Hepatic Function Matched to Mild Hepatic Function.

Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg.

Each participant with normal hepatic function was matched to a participant with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.

Moderate Hepatic Impairment. Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Matched to Moderate Hepatic Function.

Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg.

Each participant with normal hepatic function was matched to a participant with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.

Severe Hepatic Function Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Matched to Severe Hepatic Function.

Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg.

Each participant with normal hepatic function was matched to a participant with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled


Measured Values
   Mild Hepatic Impairment   Normal Hepatic Function Matched to Mild Hepatic Function.   Moderate Hepatic Impairment.   Normal Hepatic Function Matched to Moderate Hepatic Function.   Severe Hepatic Function   Normal Hepatic Function Matched to Severe Hepatic Function. 
Participants Analyzed   7   6   7   7   3   5 
Unbound Brexpiprazole AUC Calculated From Time Zero to Infinity (AUC∞,u) 
[Units: ng*h/mL]
Mean (Standard Deviation)
 8.59  (5.29)   5.85  (3.11)   8.50  (2.17)   5.62  (3.13)   3.49  (0.848)   3.36  (0.871) 


Statistical Analysis 1 for Unbound Brexpiprazole AUC Calculated From Time Zero to Infinity (AUC∞,u)
Groups [1] Mild Hepatic Impairment vs. Normal Hepatic Function Matched to Mild Hepatic Function.
Statistical Test Type [2] Non-Inferiority or Equivalence
Statistical Method [3] Mixed effect analysis of variance
Geometic Mean Ratio [4] 1.255
90% Confidence Interval 0.702 to 2.244
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The primary comparison was each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the primary PK parameters between each hepatic disease group and the control group, the 90% confidence interval (CI) for the difference in the means of the log-transformed data was calculated using a mixed effect analysis of variance.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normal-theory CIs, this approach was equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Other relevant estimation information:
  Due to the nature of the normal-theory CIs, this approach is equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance.

Statistical Analysis 2 for Unbound Brexpiprazole AUC Calculated From Time Zero to Infinity (AUC∞,u)
Groups [1] Moderate Hepatic Impairment. vs. Normal Hepatic Function Matched to Moderate Hepatic Function.
Statistical Test Type [2] Non-Inferiority or Equivalence
Statistical Method [3] Mixed effect analysis of variance
Geometric Mean Ratio [4] 1.727
90% Confidence Interval 0.977 to 3.052
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The primary comparison was each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the primary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the log-transformed data was calculated using a mixed effect analysis of variance.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normal-theory CIs, this approach was equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Other relevant estimation information:
  Due to the nature of the normal-theory CIs, this approach is equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance.

Statistical Analysis 3 for Unbound Brexpiprazole AUC Calculated From Time Zero to Infinity (AUC∞,u)
Groups [1] Severe Hepatic Function vs. Normal Hepatic Function Matched to Severe Hepatic Function.
Statistical Test Type [2] Non-Inferiority or Equivalence
Statistical Method [3] Mixed effect analysis of variance
Geometic Mean Ratio [4] 1.041
90% Confidence Interval 0.506 to 2.142
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The primary comparison was each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the primary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the log-transformed data was calculated using a mixed effect analysis of variance
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normal-theory CIs, this approach was equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Other relevant estimation information:
  Due to the nature of the normal-theory CIs, this approach is equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance.



3.  Primary:   Unbound Maximum Plasma Concentration of Brexpiprazole (Cmax,u)   [ Time Frame: Day 1 to Day 8 ]

Measure Type Primary
Measure Title Unbound Maximum Plasma Concentration of Brexpiprazole (Cmax,u)
Measure Description

Blood samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose/ET.

Cmax,u is the highest measured unbound plasma concentration during the dosing interval.

Time Frame Day 1 to Day 8  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations.

Reporting Groups
  Description
Mild Hepatic Impairment Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Matched to Mild Hepatic Function.

Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg.

Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.

Moderate Hepatic Impairment Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Matched to Moderate Hepatic Function.

Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg.

Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.

Severe Hepatic Impairment Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Matched to Severe Hepatic Function.

Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg.

Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled


Measured Values
   Mild Hepatic Impairment   Normal Hepatic Function Matched to Mild Hepatic Function.   Moderate Hepatic Impairment   Normal Hepatic Function Matched to Moderate Hepatic Function.   Severe Hepatic Impairment   Normal Hepatic Function Matched to Severe Hepatic Function. 
Participants Analyzed   8   8   8   8   6   6 
Unbound Maximum Plasma Concentration of Brexpiprazole (Cmax,u) 
[Units: ng/mL]
Mean (Standard Deviation)
 0.104  (0.0259)   0.114  (0.0270)   0.0648  (0.0143)   0.0779  (0.0224)   0.0392  (0.0105)   0.0760  (0.0258) 


Statistical Analysis 1 for Unbound Maximum Plasma Concentration of Brexpiprazole (Cmax,u)
Groups [1] Mild Hepatic Impairment vs. Normal Hepatic Function Matched to Mild Hepatic Function.
Statistical Test Type [2] Non-Inferiority or Equivalence
Statistical Method [3] Mixed effect analysis of variance
Geometric Mean Ratio [4] 0.904
90% Confidence Interval 0.707 to 1.156
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The primary comparison was each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the primary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the log-transformed data was calculated using a mixed effect analysis of variance
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normal-theory CIs, this approach was equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Other relevant estimation information:
  Due to the nature of the normal-theory CIs, this approach is equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance.

Statistical Analysis 2 for Unbound Maximum Plasma Concentration of Brexpiprazole (Cmax,u)
Groups [1] Moderate Hepatic Impairment vs. Normal Hepatic Function Matched to Moderate Hepatic Function.
Statistical Test Type [2] Non-Inferiority or Equivalence
Statistical Method [3] Mixed effect analysis of variance
Geometric Mean Ratio [4] 0.850
90% Confidence Interval 0.665 to 1.087
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The primary comparison was each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the primary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the log-transformed data was calculated using a mixed effect analysis of variance
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normal-theory CIs, this approach was equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Other relevant estimation information:
  Due to the nature of the normal-theory CIs, this approach is equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance.

Statistical Analysis 3 for Unbound Maximum Plasma Concentration of Brexpiprazole (Cmax,u)
Groups [1] Severe Hepatic Impairment vs. Normal Hepatic Function Matched to Severe Hepatic Function.
Statistical Test Type [2] Non-Inferiority or Equivalence
Statistical Method [3] Mixed effect analysis of variance
Geometric Mean Ratio [4] 0.531
90% Confidence Interval 0.399 to 0.705
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The primary comparison was each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the primary PK parameters between each hepatic disease group and the control group, the 90% confidence interval (CI) for the difference in the means of the log-transformed data was calculated using a mixed effect analysis of variance
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normal-theory CIs, this approach was equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Other relevant estimation information:
  Due to the nature of the normal-theory CIs, this approach is equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance.



4.  Secondary:   Area Under the Curve of Brexpiprazole Calculated to the Last Observable Concentration at Time t (AUCt)   [ Time Frame: Day 1 to Day 8 ]

Measure Type Secondary
Measure Title Area Under the Curve of Brexpiprazole Calculated to the Last Observable Concentration at Time t (AUCt)
Measure Description

Blood samples were taken at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose/ET.

AUCt= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t) The AUCt was estimated using the linear trapezoidal rule.

Time Frame Day 1 to Day 8  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations.

Reporting Groups
  Description
Mild Hepatic Impairment Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Matched to Mild Hepatic Function.

Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg.

Each participant with normal hepatic function was matched to a participant with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.

Moderate Hepatic Impairment Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Matched to Moderate Hepatic Function.

Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg.

Each participant with normal hepatic function was matched to a participant with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.

Severe Hepatic Impairment Participants with normal hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Matched to Severe Hepatic Function.

Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg.

Each participant with normal hepatic function was matched to a particpant with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.


Measured Values
   Mild Hepatic Impairment   Normal Hepatic Function Matched to Mild Hepatic Function.   Moderate Hepatic Impairment   Normal Hepatic Function Matched to Moderate Hepatic Function.   Severe Hepatic Impairment   Normal Hepatic Function Matched to Severe Hepatic Function. 
Participants Analyzed   8   8   8   8   6   6 
Area Under the Curve of Brexpiprazole Calculated to the Last Observable Concentration at Time t (AUCt) 
[Units: ng*h/mL]
Mean (Standard Deviation)
 1271  (569)   1145  (539)   1213  (405)   1048  (422)   622  (163)   817  (306) 


Statistical Analysis 1 for Area Under the Curve of Brexpiprazole Calculated to the Last Observable Concentration at Time t (AUCt)
Groups [1] Mild Hepatic Impairment vs. Normal Hepatic Function Matched to Mild Hepatic Function.
Statistical Test Type [2] Non-Inferiority or Equivalence
Statistical Method [3] Mixed effect analysis of variance
Geometric Mean Ratio [4] 1.103
90% Confidence Interval 0.774 to 1.573
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The secondary comparisons were each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the secondary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the log-transformed data was calculated using a mixed effect analysis of variance.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normal-theory CIs, this approach was equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Other relevant estimation information:
  Due to the nature of the normal-theory CIs, this approach is equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance.

Statistical Analysis 2 for Area Under the Curve of Brexpiprazole Calculated to the Last Observable Concentration at Time t (AUCt)
Groups [1] Moderate Hepatic Impairment vs. Normal Hepatic Function Matched to Moderate Hepatic Function.
Statistical Test Type [2] Non-Inferiority or Equivalence
Statistical Method [3] Mixed effect analysis of variance
Geometric Mean Ratio [4] 1.199
90% Confidence Interval 0.841 to 1.710
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The secondary comparisons were each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the secondary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the log-transformed data was calculated using a mixed effect analysis of variance.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normal-theory CIs, this approach was equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Other relevant estimation information:
  Due to the nature of the normal-theory CIs, this approach is equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance.

Statistical Analysis 3 for Area Under the Curve of Brexpiprazole Calculated to the Last Observable Concentration at Time t (AUCt)
Groups [1] Severe Hepatic Impairment vs. Normal Hepatic Function Matched to Severe Hepatic Function.
Statistical Test Type [2] Non-Inferiority or Equivalence
Statistical Method [3] Mixed effect analysis of variance
Geometric Mean Ratio [4] 0.790
90% Confidence Interval 0.524 to 1.189
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The secondary comparisons were each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the secondary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the log-transformed data was calculated using a mixed effect analysis of variance.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normal-theory CIs, this approach was equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Other relevant estimation information:
  Due to the nature of the normal-theory CIs, this approach is equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance.



5.  Secondary:   Area Under the Concentration Time Curve of Brexpiprazole From Time Zero to Infinity (AUC∞)   [ Time Frame: Day 1 to Day 8 ]

Measure Type Secondary
Measure Title Area Under the Concentration Time Curve of Brexpiprazole From Time Zero to Infinity (AUC∞)
Measure Description

Blood samples were taken at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose/ET.

AUC (0 - ∞)= AUC from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞).

The AUC∞ was estimated using the linear trapezoidal rule

Time Frame Day 1 to Day 8  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations.

Reporting Groups
  Description
Mild Hepatic Impairment Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Matched to Mild Hepatic Function.

Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg.

Each participant with normal hepatic function was matched to a participant with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participant with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.

Moderate Hepatic Impairment Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Matched to Moderate Hepatic Function.

Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg.

Each participant with normal hepatic function was matched to a participant with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.

Severe Hepatic Impairment Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Matched to Severe Hepatic Function.

Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg.

Each participant with normal hepatic function was matched to a participant ith hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.


Measured Values
   Mild Hepatic Impairment   Normal Hepatic Function Matched to Mild Hepatic Function.   Moderate Hepatic Impairment   Normal Hepatic Function Matched to Moderate Hepatic Function.   Severe Hepatic Impairment   Normal Hepatic Function Matched to Severe Hepatic Function. 
Participants Analyzed   7   6   7   7   3   5 
Area Under the Concentration Time Curve of Brexpiprazole From Time Zero to Infinity (AUC∞) 
[Units: ng*h/mL]
Mean (Standard Deviation)
 1827  (1103)   1393  (881)   1960  (579)   1345  (697)   831  (234)   788  (230) 


Statistical Analysis 1 for Area Under the Concentration Time Curve of Brexpiprazole From Time Zero to Infinity (AUC∞)
Groups [1] Mild Hepatic Impairment vs. Normal Hepatic Function Matched to Mild Hepatic Function.
Statistical Test Type [2] Non-Inferiority or Equivalence
Statistical Method [3] Mixed effect analysis of variance
Geometric Mean Ratio [4] 1.241
90% Confidence Interval 0.719 to 2.143
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The secondary comparisons were each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the secondary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the log-transformed data was calculated using a mixed effect analysis of variance.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normal-theory CIs, this approach was equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Other relevant estimation information:
  Due to the nature of the normal-theory CIs, this approach is equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance.

Statistical Analysis 2 for Area Under the Concentration Time Curve of Brexpiprazole From Time Zero to Infinity (AUC∞)
Groups [1] Moderate Hepatic Impairment vs. Normal Hepatic Function Matched to Moderate Hepatic Function.
Statistical Test Type [2] Non-Inferiority or Equivalence
Statistical Method [3] Mixed effect analysis of variance
Geometric Mean Ratio [4] 1.604
90% Confidence Interval 0.942 to 2.732
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The secondary comparisons were each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the secondary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the log-transformed data was calculated using a mixed effect analysis of variance.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normal-theory CIs, this approach was equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Other relevant estimation information:
  Due to the nature of the normal-theory CIs, this approach is equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance.

Statistical Analysis 3 for Area Under the Concentration Time Curve of Brexpiprazole From Time Zero to Infinity (AUC∞)
Groups [1] Severe Hepatic Impairment vs. Normal Hepatic Function Matched to Severe Hepatic Function.
Statistical Test Type [2] Non-Inferiority or Equivalence
Statistical Method [3] Mixed effect analysis of variance
Geometric Mean Ratio [4] 1.077
90% Confidence Interval 0.540 to 2.146
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The secondary comparisons were each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the secondary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the log-transformed data was calculated using a mixed effect analysis of variance.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normal-theory CIs, this approach was equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Other relevant estimation information:
  Due to the nature of the normal-theory CIs, this approach is equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance.



6.  Secondary:   Maximum Plasma Concentration of Brexpiprazole (Cmax)   [ Time Frame: Day 1 to Day 8 ]

Measure Type Secondary
Measure Title Maximum Plasma Concentration of Brexpiprazole (Cmax)
Measure Description

Blood samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose/ET.

Cmax is the highest measured concentration of the drug during the dosing interval.

Actual blood sample times were used for PK calculations. Values for Cmax and tmax were determined directly from the observed data.

Time Frame Day 1 to Day 8  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations.

Reporting Groups
  Description
Mild Hepatic Impairment Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Matched to Mild Hepatic Function.

Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg.

Each participant with normal hepatic function was matched to a participant with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.

Moderate Hepatic Impairment Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Matched to Moderate Hepatic Function.

Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg.

Each participant with normal hepatic function was matched to a participant with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.

Severe Hepatic Impairment Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Matched to Severe Hepatic Function.

Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg.

Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.


Measured Values
   Mild Hepatic Impairment   Normal Hepatic Function Matched to Mild Hepatic Function.   Moderate Hepatic Impairment   Normal Hepatic Function Matched to Moderate Hepatic Function.   Severe Hepatic Impairment   Normal Hepatic Function Matched to Severe Hepatic Function. 
Participants Analyzed   8   8   8   8   6   6 
Maximum Plasma Concentration of Brexpiprazole (Cmax) 
[Units: ng/mL]
Mean (Standard Deviation)
 22.9  (7.60)   26.7  (9.09)   14.6  (4.63)   19.3  (4.98)   7.65  (2.69)   17.7  (7.38) 


Statistical Analysis 1 for Maximum Plasma Concentration of Brexpiprazole (Cmax)
Groups [1] Mild Hepatic Impairment vs. Normal Hepatic Function Matched to Mild Hepatic Function.
Statistical Test Type [2] Non-Inferiority or Equivalence
Statistical Method [3] Mixed effect analysis of variance
Geometric mean ratio [4] 0.856
90% Confidence Interval 0.691 to 1.059
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The secondary comparisons were each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the secondary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the log-transformed data was calculated using a mixed effect analysis of variance.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normal-theory CIs, this approach was equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Other relevant estimation information:
  Due to the nature of the normal-theory CIs, this approach is equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance.

Statistical Analysis 2 for Maximum Plasma Concentration of Brexpiprazole (Cmax)
Groups [1] Moderate Hepatic Impairment vs. Normal Hepatic Function Matched to Moderate Hepatic Function.
Statistical Test Type [2] Non-Inferiority or Equivalence
Statistical Method [3] Mixed effect analysis of variance
Geometric Mean Ratio [4] 0.742
90% Confidence Interval 0.599 to 0.918
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The secondary comparisons were each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the secondary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the log-transformed data was calculated using a mixed effect analysis of variance.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normal-theory CIs, this approach was equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Other relevant estimation information:
  Due to the nature of the normal-theory CIs, this approach is equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance.

Statistical Analysis 3 for Maximum Plasma Concentration of Brexpiprazole (Cmax)
Groups [1] Severe Hepatic Impairment vs. Normal Hepatic Function Matched to Severe Hepatic Function.
Statistical Test Type [2] Non-Inferiority or Equivalence
Statistical Method [3] Mixed effect analysis of variance
Geometric Mean Ratio [4] 0.451
90% Confidence Interval 0.352 to 0.577
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The secondary comparisons were each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the secondary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the log-transformed data was calculated using a mixed effect analysis of variance.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normal-theory CIs, this approach was equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Other relevant estimation information:
  Due to the nature of the normal-theory CIs, this approach is equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance.



7.  Secondary:   Time to Cmax of Brexiprazole (Tmax)   [ Time Frame: Day 1 to Day 8 ]

Measure Type Secondary
Measure Title Time to Cmax of Brexiprazole (Tmax)
Measure Description

Blood samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose/ET.

Tmax is the time taken to reach highest measured concentration of the drug during the dosing interval.

Actual blood sample times were used for PK calculations. Values for Cmax and tmax were determined directly from the observed data.

Time Frame Day 1 to Day 8  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations.

Reporting Groups
  Description
Mild Hepatic Impairment Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Matched to Mild Hepatic Function.

Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg.

Each participant with normal hepatic function was matched to a participant with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.

Moderate Hepatic Impairment Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Matched to Moderate Hepatic Function.

Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg.

Each participant with normal hepatic function was matched to a participant with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.

Severe Hepatic Function Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Matched to Severe Hepatic Function.

Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg.

Each participant with normal hepatic function was matched to a participant with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.


Measured Values
   Mild Hepatic Impairment   Normal Hepatic Function Matched to Mild Hepatic Function.   Moderate Hepatic Impairment   Normal Hepatic Function Matched to Moderate Hepatic Function.   Severe Hepatic Function   Normal Hepatic Function Matched to Severe Hepatic Function. 
Participants Analyzed   8   8   8   8   6   6 
Time to Cmax of Brexiprazole (Tmax) 
[Units: h]
Median (Full Range)
 3.50 
 (1.00 to 5.00) 
 3.50 
 (2.00 to 5.00) 
 4.50 
 (3.00 to 24.0) 
 4.50 
 (1.00 to 6.00) 
 5.00 
 (4.00 to 24.0) 
 5.00 
 (2.00 to 6.00) 

No statistical analysis provided for Time to Cmax of Brexiprazole (Tmax)



8.  Secondary:   Apparent Clearance of Brexpiprazole From Plasma After Extravascular Administration (CL/F)   [ Time Frame: Day 1 to Day 8 ]

Measure Type Secondary
Measure Title Apparent Clearance of Brexpiprazole From Plasma After Extravascular Administration (CL/F)
Measure Description

The value of CL/F (brexpiprazole only) was determined as Dose/AUC∞.

Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population PK modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.

Time Frame Day 1 to Day 8  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations.

Reporting Groups
  Description
Mild Hepatic Impairment Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Matched to Mild Hepatic Function.

Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg.

Each participant with normal hepatic function was matched to a participants with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Partipants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.

Moderate Hepatic Impairment Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Matched to Moderate Hepatic Function.

Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg.

Each participant with normal hepatic function was matched to a participant with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.

Severe Hepatic Impairment Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Matched to Severe Hepatic Function.

Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg.

Each participant with normal hepatic function was matched to a participant with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.


Measured Values
   Mild Hepatic Impairment   Normal Hepatic Function Matched to Mild Hepatic Function.   Moderate Hepatic Impairment   Normal Hepatic Function Matched to Moderate Hepatic Function.   Severe Hepatic Impairment   Normal Hepatic Function Matched to Severe Hepatic Function. 
Participants Analyzed   7   6   7   6   3   5 
Apparent Clearance of Brexpiprazole From Plasma After Extravascular Administration (CL/F) 
[Units: mL/h/kg]
Mean (Standard Deviation)
 24.5  (28.2)   25.4  (12.3)   13.8  (2.72)   26.0  (19.2)   28.2  (6.70)   34.2  (16.3) 

No statistical analysis provided for Apparent Clearance of Brexpiprazole From Plasma After Extravascular Administration (CL/F)



9.  Secondary:   Unbound Fraction of Brexpiprazole in Plasma (fu)   [ Time Frame: Day 1 to Day 8 ]

Measure Type Secondary
Measure Title Unbound Fraction of Brexpiprazole in Plasma (fu)
Measure Description Blood samples were taken at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose/ET.
Time Frame Day 1 to Day 8  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations.

Reporting Groups
  Description
Mild Hepatic Function Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Matched to Mild Hepatic Function.

Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg.

Each participant with normal hepatic function was matched to a participant with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.

Moderate Hepatic Function Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Matched to Moderate Hepatic Function.

Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg.

Each participant with normal hepatic function was matched to a participant with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.

Severe Hepatic Function Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Matched to Severe Hepatic Function.

Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg.

Each participant with normal hepatic function was matched to a participant with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.


Measured Values
   Mild Hepatic Function   Normal Hepatic Function Matched to Mild Hepatic Function.   Moderate Hepatic Function   Normal Hepatic Function Matched to Moderate Hepatic Function.   Severe Hepatic Function   Normal Hepatic Function Matched to Severe Hepatic Function. 
Participants Analyzed   8   8   8   8   6   6 
Unbound Fraction of Brexpiprazole in Plasma (fu) 
[Units: % unbound drug in the urine]
Mean (Standard Deviation)
 0.472  (0.0840)   0.451  (0.112)   0.462  (0.0786)   0.400  (0.0442)   0.544  (0.186)   0.450  (0.0795) 

No statistical analysis provided for Unbound Fraction of Brexpiprazole in Plasma (fu)



10.  Secondary:   Apparent Unbound Clearance of Brexpiprazole From Plasma After Extravascular Administration (CLu/F)   [ Time Frame: Day 1 to Day 8 ]

Measure Type Secondary
Measure Title Apparent Unbound Clearance of Brexpiprazole From Plasma After Extravascular Administration (CLu/F)
Measure Description

Blood samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose/ET.

The value of CLu/F (brexpiprazole only) was determined as dose normalized unbound area under the concentration-time curve from time zero to infinity (Dose/AUC∞,u).

Time Frame Day 1 to Day 8  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations.

Reporting Groups
  Description
Mild Hepatic Impairment Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Matched to Mild Hepatic Function.

Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg.

Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.

Moderate Hepatic Function Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Matched to Moderate Hepatic Function.

Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg.

Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled

Severe Hepatic Function Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Matched to Severe Hepatic Function.

Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg.

Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled


Measured Values
   Mild Hepatic Impairment   Normal Hepatic Function Matched to Mild Hepatic Function.   Moderate Hepatic Function   Normal Hepatic Function Matched to Moderate Hepatic Function.   Severe Hepatic Function   Normal Hepatic Function Matched to Severe Hepatic Function. 
Participants Analyzed   7   6   7   7   3   5 
Apparent Unbound Clearance of Brexpiprazole From Plasma After Extravascular Administration (CLu/F) 
[Units: mL/h/kg]
Mean (Standard Deviation)
 5674  (7165)   5730  (2944)   3115  (494)   6768  (5833)   6598  (1182)   7697  (2653) 

No statistical analysis provided for Apparent Unbound Clearance of Brexpiprazole From Plasma After Extravascular Administration (CLu/F)



11.  Secondary:   Terminal-phase Elimination Half-life of Brexpiprazole (t1/2,z)   [ Time Frame: Day 1 to Day 8 ]

Measure Type Secondary
Measure Title Terminal-phase Elimination Half-life of Brexpiprazole (t1/2,z)
Measure Description

Blood samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose/ET.

The t1/2,z was determined as (ln2)/λz.

Terminal-phase elimination half-life is the time measured for the plasma concentration to decrease by one half.

Time Frame Day 1 to Day 8  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations.

Reporting Groups
  Description
Mild Hepatic Function Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Matched to Mild Hepatic Function.

Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg.

Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.

Moderate Hepatic Function Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Matched to Moderate Hepatic Function.

Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg.

Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.

Sever Hepatic Function Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Matched to Severe Hepatic Function.

Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg.

Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled


Measured Values
   Mild Hepatic Function   Normal Hepatic Function Matched to Mild Hepatic Function.   Moderate Hepatic Function   Normal Hepatic Function Matched to Moderate Hepatic Function.   Sever Hepatic Function   Normal Hepatic Function Matched to Severe Hepatic Function. 
Participants Analyzed   7   6   7   7   3   5 
Terminal-phase Elimination Half-life of Brexpiprazole (t1/2,z) 
[Units: h]
Mean (Standard Deviation)
 103  (51.1)   64.7  (24.6)   116  (25.8)   64.2  (26.2)   81.1  (17.1)   51.4  (8.21) 

No statistical analysis provided for Terminal-phase Elimination Half-life of Brexpiprazole (t1/2,z)



12.  Secondary:   Renal Clearance (CLr) of Brexipiprazole   [ Time Frame: Day 1 to Day 8 ]

Measure Type Secondary
Measure Title Renal Clearance (CLr) of Brexipiprazole
Measure Description

Urine samples were taken at pre-dose and during the following increments: 0 to 24, 24 to 48, 48 to 72, 72 to 96, 96 to 120, 120 to 144, and 144 to 168 hours postdose.

The value of CLr was calculated as Ae,u/AUCt.

Time Frame Day 1 to Day 8  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations.

Reporting Groups
  Description
Mild Hepatic Impairment Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Matched to Mild Hepatic Function.

Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg.

Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.

Moderate Hepatic Impairment Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Matched to Moderate Hepatic Function.

Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg.

Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.

Severe Hepatic Impairment Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Matched to Severe Hepatic Function.

Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg.

Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.


Measured Values
   Mild Hepatic Impairment   Normal Hepatic Function Matched to Mild Hepatic Function.   Moderate Hepatic Impairment   Normal Hepatic Function Matched to Moderate Hepatic Function.   Severe Hepatic Impairment   Normal Hepatic Function Matched to Severe Hepatic Function. 
Participants Analyzed   8   8   8   8   6   6 
Renal Clearance (CLr) of Brexipiprazole 
[Units: mL/h/kg]
Mean (Standard Deviation)
 0.0468  (0.0353)   0.0263  (0.0244)   0.0360  (0.0286)   0.0422  (0.0383)   0.0402  (0.0872)   0.0193  (0.0203) 

No statistical analysis provided for Renal Clearance (CLr) of Brexipiprazole



13.  Secondary:   Cumulative Amount of Brexpiprazole Excreted Into the Urine (Ae,u)   [ Time Frame: Day 1 to Day 8 ]

Measure Type Secondary
Measure Title Cumulative Amount of Brexpiprazole Excreted Into the Urine (Ae,u)
Measure Description

Urine samples were taken at pre-dose and during the following increments: 0 to 24, 24 to 48, 48 to 72, 72 to 96, 96 to 120, 120 to 144, and 144 to 168 hours postdose.

The value of Ae,u was calculated as the summation of urine concentration × urine volume from each collection interval

Time Frame Day 1 to Day 8  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations.

Reporting Groups
  Description
Mild Hepatic Function Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Matched to Mild Hepatic Function.

Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg.

Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.

Moderate Hepatic Function Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Matched to Moderate Hepatic Function.

Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg.

Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.

Severe Hepatic Function Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Matched to Severe Hepatic Function.

Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg.

Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.


Measured Values
   Mild Hepatic Function   Normal Hepatic Function Matched to Mild Hepatic Function.   Moderate Hepatic Function   Normal Hepatic Function Matched to Moderate Hepatic Function.   Severe Hepatic Function   Normal Hepatic Function Matched to Severe Hepatic Function. 
Participants Analyzed   8   8   8   8   6   6 
Cumulative Amount of Brexpiprazole Excreted Into the Urine (Ae,u) 
[Units: Ng]
Mean (Standard Deviation)
 4511  (3808)   1854  (1500)   3522  (2740)   3837  (3358)   2090  (4699)   1326  (1427) 

No statistical analysis provided for Cumulative Amount of Brexpiprazole Excreted Into the Urine (Ae,u)



14.  Secondary:   Fraction of Systemically Available Brexpiprazole Excreted Into the Urine (fe,u)   [ Time Frame: Day 1 to Day 8 ]

Measure Type Secondary
Measure Title Fraction of Systemically Available Brexpiprazole Excreted Into the Urine (fe,u)
Measure Description

Urine samples were taken at pre-dose and during the following increments: 0 to 24, 24 to 48, 48 to 72, 72 to 96, 96 to 120, 120 to 144, and 144 to 168 hours postdose..

The value of fe,u was calculated as 100 × Ae,u/Dose.

Time Frame Day 1 to Day 8  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations.

Reporting Groups
  Description
Mild Hepatic Impairment Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Matched to Mild Hepatic Function.

Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg.

Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.

Moderate Hepatic Impairment Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Matched to Moderate Hepatic Function

Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg.

Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.

Severe Hepatic Impairment Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Matched to Severe Hepatic Function.

Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg.

Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.


Measured Values
   Mild Hepatic Impairment   Normal Hepatic Function Matched to Mild Hepatic Function.   Moderate Hepatic Impairment   Normal Hepatic Function Matched to Moderate Hepatic Function   Severe Hepatic Impairment   Normal Hepatic Function Matched to Severe Hepatic Function. 
Participants Analyzed   8   8   8   8   6   6 
Fraction of Systemically Available Brexpiprazole Excreted Into the Urine (fe,u) 
[Units: % of drug in urine]
Mean (Standard Deviation)
 0.226  (0.190)   0.0927  (0.0750)   0.176  (0.137)   0.192  (0.168)   0.104  (0.235)   0.0663  (0.0713) 

No statistical analysis provided for Fraction of Systemically Available Brexpiprazole Excreted Into the Urine (fe,u)



15.  Secondary:   AUCt for DM-3411 Metabolite   [ Time Frame: Day 1 to Day 8 ]

Measure Type Secondary
Measure Title AUCt for DM-3411 Metabolite
Measure Description

Blood samples were taken at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose/ET.

AUCt= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t)

The AUCt was estimated using the linear trapezoidal rule.

Time Frame Day 1 to Day 8  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations.

Reporting Groups
  Description
Mild Hepatic Impairment Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Matched to Mild Hepatic Function.

Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg.

Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.

Moderate Hepatic Impairment Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Matched to Moderate Hepatic Function.

Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg.

Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.

Severe Hepatic Impairment Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Matched to Severe Hepatic Function.

Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg.

Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.


Measured Values
   Mild Hepatic Impairment   Normal Hepatic Function Matched to Mild Hepatic Function.   Moderate Hepatic Impairment   Normal Hepatic Function Matched to Moderate Hepatic Function.   Severe Hepatic Impairment   Normal Hepatic Function Matched to Severe Hepatic Function. 
Participants Analyzed   8   8   8   8   6   6 
AUCt for DM-3411 Metabolite 
[Units: ng*h/mL]
Mean (Standard Deviation)
 380  (195)   683  (246)   284  (164)   486  (263)   151  (51.4)   479  (226) 


Statistical Analysis 1 for AUCt for DM-3411 Metabolite
Groups [1] Mild Hepatic Impairment vs. Normal Hepatic Function Matched to Mild Hepatic Function.
Statistical Test Type [2] Non-Inferiority or Equivalence
Statistical Method [3] Mixed effect analysis of variance
Geometric Mean Ratio [4] 0.509
90% Confidence Interval 0.346 to 0.748
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The secondary comparisons were each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the secondary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the log-transformed data was calculated using a mixed effect analysis of variance.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normal-theory CIs, this approach was equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for AUCt for DM-3411 Metabolite
Groups [1] Moderate Hepatic Impairment vs. Normal Hepatic Function Matched to Moderate Hepatic Function.
Statistical Test Type [2] Non-Inferiority or Equivalence
Statistical Method [3] Mixed effect analysis of variance
Geometric Mean Ratio [4] 0.586
90% Confidence Interval 0.399 to 0.861
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The secondary comparisons were each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the secondary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the log-transformed data was calculated using a mixed effect analysis of variance.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normal-theory CIs, this approach was equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Other relevant estimation information:
  Due to the nature of the normal-theory CIs, this approach is equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance.

Statistical Analysis 3 for AUCt for DM-3411 Metabolite
Groups [1] Severe Hepatic Impairment vs. Normal Hepatic Function Matched to Severe Hepatic Function.
Statistical Test Type [2] Non-Inferiority or Equivalence
Statistical Method [3] Mixed effect analysis of variance
Geometric Mean Ratio [4] 0.334
90% Confidence Interval 0.214 to 0.521
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The secondary comparisons were each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the secondary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the log-transformed data was calculated using a mixed effect analysis of variance.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normal-theory CIs, this approach was equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Other relevant estimation information:
  Due to the nature of the normal-theory CIs, this approach is equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance.



16.  Secondary:   AUC∞ for DM-3411 Metabolite   [ Time Frame: Day 1 to Day 8 ]

Measure Type Secondary
Measure Title AUC∞ for DM-3411 Metabolite
Measure Description

Blood samples were taken at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose/ET.

The AUC∞ were estimated using the linear trapezoidal rule.

Time Frame Day 1 to Day 8  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations.

Reporting Groups
  Description
Mild Hepatic Impairment Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Matched to Mild Hepatic Function.

Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg.

Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.

Moderate Hepatic Impairment Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Matched to Moderate Hepatic Function.

Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg.

Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.

Severe Hepatic Impairment Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Matched to Severe Hepatic Function.

Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg.

Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.


Measured Values
   Mild Hepatic Impairment   Normal Hepatic Function Matched to Mild Hepatic Function.   Moderate Hepatic Impairment   Normal Hepatic Function Matched to Moderate Hepatic Function.   Severe Hepatic Impairment   Normal Hepatic Function Matched to Severe Hepatic Function. 
Participants Analyzed   5   6   6   6   4   3 
AUC∞ for DM-3411 Metabolite 
[Units: ng*h/mL]
Mean (Standard Deviation)
 489  (210)   692  (259)   382  (262)   530  (211)   187  (67.2)   329  (167) 


Statistical Analysis 1 for AUC∞ for DM-3411 Metabolite
Groups [1] Mild Hepatic Impairment vs. Normal Hepatic Function Matched to Mild Hepatic Function.
Statistical Test Type [2] Non-Inferiority or Equivalence
Statistical Method [3] Mixed effect analysis of variance
Geometric Mean Ratio [4] 0.716
90% Confidence Interval 0.445 to 1.153
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The secondary comparisons were each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the secondary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the log-transformed data was calculated using a mixed effect analysis of variance.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normal-theory CIs, this approach was equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for AUC∞ for DM-3411 Metabolite
Groups [1] Moderate Hepatic Impairment vs. Normal Hepatic Function Matched to Moderate Hepatic Function.
Statistical Test Type [2] Non-Inferiority or Equivalence
Statistical Method [3] Mixed effect analysis of variance
Geometric Mean Ratio [4] 0.594
90% Confidence Interval 0.378 to 0.934
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The secondary comparisons were each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the secondary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the log-transformed data was calculated using a mixed effect analysis of variance.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normal-theory CIs, this approach was equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 3 for AUC∞ for DM-3411 Metabolite
Groups [1] Severe Hepatic Impairment vs. Normal Hepatic Function Matched to Severe Hepatic Function.
Statistical Test Type [2] Non-Inferiority or Equivalence
Statistical Method [3] Mixed effect analysis of variance
Geometric Mean Ratio [4] 0.561
90% Confidence Interval 0.308 to 1.022
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The secondary comparisons were each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the secondary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the log-transformed data was calculated using a mixed effect analysis of variance.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normal-theory CIs, this approach was equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



17.  Secondary:   Cmax for DM-3411 Metabolite   [ Time Frame: Day 1 to Day 8 ]

Measure Type Secondary
Measure Title Cmax for DM-3411 Metabolite
Measure Description Blood samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose/ET. Cmax is the highest measured concentration of the metabolite during the dosing interval.
Time Frame Day 1 to Day 8  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations.

Reporting Groups
  Description
Mild Hepatic Impairment Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Matched to Mild Hepatic Function.

Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg.

Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.

Moderate Hepatic Impairment Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Matched to Moderate Hepatic Function.

Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg.

Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled

Severe Hepatic Impairment Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Matched to Severe Hepatic Function.

Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg.

Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.


Measured Values
   Mild Hepatic Impairment   Normal Hepatic Function Matched to Mild Hepatic Function.   Moderate Hepatic Impairment   Normal Hepatic Function Matched to Moderate Hepatic Function.   Severe Hepatic Impairment   Normal Hepatic Function Matched to Severe Hepatic Function. 
Participants Analyzed   8   8   8   8   6   6 
Cmax for DM-3411 Metabolite 
[Units: ng/mL]
Mean (Standard Deviation)
 6.49  (5.13)   10.5  (4.26)   3.19  (1.56)   7.25  (4.83)   2.15  (0.880)   7.13  (3.73) 


Statistical Analysis 1 for Cmax for DM-3411 Metabolite
Groups [1] Mild Hepatic Impairment vs. Normal Hepatic Function Matched to Mild Hepatic Function.
Statistical Test Type [2] Non-Inferiority or Equivalence
Statistical Method [3] Mixed effect analysis of variance
Geometric Mean Ratio [4] 0.558
90% Confidence Interval 0.368 to 0.845
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The secondary comparisons were each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the secondary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the log-transformed data was calculated using a mixed effect analysis of variance.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normal-theory CIs, this approach was equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Cmax for DM-3411 Metabolite
Groups [1] Moderate Hepatic Impairment vs. Normal Hepatic Function Matched to Moderate Hepatic Function.
Statistical Test Type [2] Non-Inferiority or Equivalence
Statistical Method [3] Mixed effect analysis of variance
Geometric Mean Ratio [4] 0.516
90% Confidence Interval 0.341 to 0.781
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The secondary comparisons were each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the secondary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the log-transformed data was calculated using a mixed effect analysis of variance.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normal-theory CIs, this approach was equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 3 for Cmax for DM-3411 Metabolite
Groups [1] Severe Hepatic Impairment vs. Normal Hepatic Function Matched to Severe Hepatic Function.
Statistical Test Type [2] Non-Inferiority or Equivalence
Statistical Method [3] Mixed effect analysis of variance
Geometric Mean Ratio [4] 0.314
90% Confidence Interval 0.195 to 0.507
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The secondary comparisons were each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the secondary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the log-transformed data was calculated using a mixed effect analysis of variance.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normal-theory CIs, this approach was equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



18.  Secondary:   Tmax for DM-3411 Metabolite   [ Time Frame: Day 1 to Day 8 ]

Measure Type Secondary
Measure Title Tmax for DM-3411 Metabolite
Measure Description Blood samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose/ET. Tmax is the time taken to reach highest measured concentration of the metabolite during the dosing interval.
Time Frame Day 1 to Day 8  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations.

Reporting Groups
  Description
Mild Hepatic Function Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Matched to Mild Hepatic Function.

Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg.

Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.

Moderate Hepatic Function Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Matched to Moderate Hepatic Function.

Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg.

Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.

Severe Hepatic Function Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Matched to Severe Hepatic Function.

Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg.

Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.


Measured Values
   Mild Hepatic Function   Normal Hepatic Function Matched to Mild Hepatic Function.   Moderate Hepatic Function   Normal Hepatic Function Matched to Moderate Hepatic Function.   Severe Hepatic Function   Normal Hepatic Function Matched to Severe Hepatic Function. 
Participants Analyzed   8   8   8   8   6   6 
Tmax for DM-3411 Metabolite 
[Units: h]
Median (Full Range)
 5.00 
 (2.00 to 24.0) 
 6.00 
 (5.00 to 24.0) 
 5.00 
 (2.00 to 24.0) 
 7.00 
 (2.00 to 24.0) 
 4.5 
 (3.00 to 24.0) 
 6.00 
 (5.00 to 16.0) 

No statistical analysis provided for Tmax for DM-3411 Metabolite



19.  Secondary:   t1/2,z for DM-3411 Metabolite   [ Time Frame: Day 1 to Day 8 ]

Measure Type Secondary
Measure Title t1/2,z for DM-3411 Metabolite
Measure Description

Blood samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose/ET.

The t1/2,z was determined as (ln2)/λz.

Time Frame Day 1 to Day 8  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations.

Reporting Groups
  Description
Mild Hepatic Impairment Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Matched to Mild Hepatic Function.

Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg.

Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.

Moderate Hepatic Impairment Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Matched to Moderate Hepatic Function.

Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg.

Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.

Severe Hepatic Impairment Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Matched to Severe Hepatic Function.

Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg.

Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.


Measured Values
   Mild Hepatic Impairment   Normal Hepatic Function Matched to Mild Hepatic Function.   Moderate Hepatic Impairment   Normal Hepatic Function Matched to Moderate Hepatic Function.   Severe Hepatic Impairment   Normal Hepatic Function Matched to Severe Hepatic Function. 
Participants Analyzed   5   6   6   6   4   3 
t1/2,z for DM-3411 Metabolite 
[Units: h]
Mean (Standard Deviation)
 78.8  (37.6)   59.7  (15.7)   87.2  (45.7)   62.0  (26.4)   84.6  (12.0)   56.1  (8.25) 

No statistical analysis provided for t1/2,z for DM-3411 Metabolite



20.  Secondary:   Ae,u for DM-3411 Metabolite   [ Time Frame: Day 1 to Day 8 ]

Measure Type Secondary
Measure Title Ae,u for DM-3411 Metabolite
Measure Description

Urine samples were taken at pre-dose and during the following increments: 0 to 24, 24 to 48, 48 to 72, 72 to 96, 96 to 120, 120 to 144, and 144 to 168 hours postdose.

The value of Ae,u was calculated as the summation of urine concentration × urine volume from each collection interval.

Time Frame Day 1 to Day 8  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations.

Reporting Groups
  Description
Mild Hepatic Function Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Matched to Mild Hepatic Function.

Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg.

Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.

Moderate Hepatic Function Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Matched to Moderate Hepatic Function.

Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg.

Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled

Severe Hepatic Function Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Matched to Severe Hepatic Function.

Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg.

Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.


Measured Values
   Mild Hepatic Function   Normal Hepatic Function Matched to Mild Hepatic Function.   Moderate Hepatic Function   Normal Hepatic Function Matched to Moderate Hepatic Function.   Severe Hepatic Function   Normal Hepatic Function Matched to Severe Hepatic Function. 
Participants Analyzed   8   8   8   8   6   6 
Ae,u for DM-3411 Metabolite 
[Units: Ng]
Mean (Standard Deviation)
 67086  (25276)   81148  (23188)   68413  (16993)   71353  (41630)   48190  (14756)   83604  (34907) 

No statistical analysis provided for Ae,u for DM-3411 Metabolite



21.  Secondary:   fe,u for DM-3411 Metabolite   [ Time Frame: Day 1 to Day 8 ]

Measure Type Secondary
Measure Title fe,u for DM-3411 Metabolite
Measure Description

Urine samples were taken at pre-dose and during the following increments: 0 to 24, 24 to 48, 48 to 72, 72 to 96, 96 to 120, 120 to 144, and 144 to 168 hours postdose.

The value of fe,u was calculated as 100 × Ae,u/Dose.

Time Frame Day 1 to Day 8  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations.

Reporting Groups
  Description
Mild Hepatic Function Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Matched to Mild Hepatic Function.

Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg.

Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.

Moderate Hepatic Function Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg
Normal Hepatic Function Matched to Moderate Hepatic Function.

Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg.

Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.

Severe Hepatic Function Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Matched to Severe Hepatic Function.

Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg.

Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.


Measured Values
   Mild Hepatic Function   Normal Hepatic Function Matched to Mild Hepatic Function.   Moderate Hepatic Function   Normal Hepatic Function Matched to Moderate Hepatic Function.   Severe Hepatic Function   Normal Hepatic Function Matched to Severe Hepatic Function. 
Participants Analyzed   8   8   8   8   6   6 
fe,u for DM-3411 Metabolite 
[Units: % metabolite excreted in urine]
Mean (Standard Deviation)
 3.23  (1.22)   3.91  (1.12)   3.30  (0.819)   3.44  (2.01)   2.32  (0.712)   4.03  (1.68) 

No statistical analysis provided for fe,u for DM-3411 Metabolite



22.  Secondary:   CLr for DM-3411 Metabolite   [ Time Frame: Day 1 to Day 8 ]

Measure Type Secondary
Measure Title CLr for DM-3411 Metabolite
Measure Description

Urine samples were taken at pre-dose and during the following increments: 0 to 24, 24 to 48, 48 to 72, 72 to 96, 96 to 120, 120 to 144, and 144 to 168 hours postdose.

The value of CLr was calculated as Ae,u/AUCt.

Time Frame Day 1 to Day 8  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations.

Reporting Groups
  Description
Mild Hepatic Impairment Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Matched to Mild Hepatic Function.

Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg.

Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.

Moderate Hepatic Impairment Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Matched to Moderate Hepatic Function.

Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg.

Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.

Severe Hepatic Impairment Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Matched to Severe Hepatic Function.

Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg.

Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.


Measured Values
   Mild Hepatic Impairment   Normal Hepatic Function Matched to Mild Hepatic Function.   Moderate Hepatic Impairment   Normal Hepatic Function Matched to Moderate Hepatic Function.   Severe Hepatic Impairment   Normal Hepatic Function Matched to Severe Hepatic Function. 
Participants Analyzed   8   8   8   8   6   6 
CLr for DM-3411 Metabolite 
[Units: mL/h/kg]
Mean (Standard Deviation)
 2.67  (1.31)   1.83  (0.828)   3.96  (2.32)   1.90  (0.568)   4.08  (1.68)   2.33  (1.01) 

No statistical analysis provided for CLr for DM-3411 Metabolite



23.  Secondary:   Number of Adverse Events (AEs) Reported   [ Time Frame: From the time the Informed Consent Form was signed, throughout the 8 day study up to 30 days after study drug administration. ]

Measure Type Secondary
Measure Title Number of Adverse Events (AEs) Reported
Measure Description AEs were captured for all participants from the time the ICF was signed until the end of the study
Time Frame From the time the Informed Consent Form was signed, throughout the 8 day study up to 30 days after study drug administration.  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants who received at least one dose of study drug were included in the safety analysis.

Reporting Groups
  Description
Mild Hepatic Impairment Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Moderate Hepatic Impairment Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Severe Hepatic Impairment Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Participants with normal hepatic function (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

Measured Values
   Mild Hepatic Impairment   Moderate Hepatic Impairment   Severe Hepatic Impairment   Normal Hepatic Function 
Participants Analyzed   8   8   6   23 
Number of Adverse Events (AEs) Reported 
[Units: Events]
       
Adverse events   3   5   1   8 
Treatment emergent adverse events   3   5   1   6 
Serious adverse events   0   0   0   0 

No statistical analysis provided for Number of Adverse Events (AEs) Reported



24.  Secondary:   Number of Participants With Changes From Baseline in Vital Signs Parameters.   [ Time Frame: Day -1 to Day 8 ]

Measure Type Secondary
Measure Title Number of Participants With Changes From Baseline in Vital Signs Parameters.
Measure Description Vital signs (including blood pressure, heart rate, temperature, and respiratory rate) were assessed at Screening, Day -1, Day 1 at predose (within 45 minutes prior to dosing), and 2, 4, 6, 8, 12, 24, 72, 120, and 168/ET hours postdose. Blood pressure and heart rate were taken with the subject in the supine (performed first), sitting, and standing
Time Frame Day -1 to Day 8  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The abnormal values of vital signs values in participants are captured as serious AEs/AEs and are reported in the SAE or other AE section of this results report.

Reporting Groups
  Description
Mild Hepatic Impairment Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Moderate Hepatic Impairment Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Severe Hepatic Impairment Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Participants with normal hepatic function (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

Measured Values
   Mild Hepatic Impairment   Moderate Hepatic Impairment   Severe Hepatic Impairment   Normal Hepatic Function 
Participants Analyzed   8   8   6   23 
Number of Participants With Changes From Baseline in Vital Signs Parameters. 
[Units: Participants]
 0   0   0   0 

No statistical analysis provided for Number of Participants With Changes From Baseline in Vital Signs Parameters.



25.  Secondary:   Number of Participants With Changes From Baseline in Electrocardiogram (ECG) Parameters.   [ Time Frame: Day-1 to Day 8 ]

Measure Type Secondary
Measure Title Number of Participants With Changes From Baseline in Electrocardiogram (ECG) Parameters.
Measure Description Electrocardiograms were performed at Screening, Day -1, and Day 1 at predose (in triplicate; within 45 minutes prior to dosing), and 2, 4, 6, 8, 12, 24, 72, 120, and 168/ET hours postdose. Standard 12-lead ECGs were performed after the subject was supine and at rest for ≥ 10 minutes prior to the ECG.
Time Frame Day-1 to Day 8  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The abnormal values of ECG values in participants are captured as serious AEs/AEs and are reported in the SAE or other AE section of this results report.

Reporting Groups
  Description
Mild Hepatic Impairment Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Moderate Hepatic Impairment Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Severe Hepatic Impairment Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Participants with normal hepatic function (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

Measured Values
   Mild Hepatic Impairment   Moderate Hepatic Impairment   Severe Hepatic Impairment   Normal Hepatic Function 
Participants Analyzed   8   8   6   23 
Number of Participants With Changes From Baseline in Electrocardiogram (ECG) Parameters. 
[Units: Participants]
 0   0   0   0 

No statistical analysis provided for Number of Participants With Changes From Baseline in Electrocardiogram (ECG) Parameters.



26.  Secondary:   Number of Participants With Changes From Baseline in Serum Chemistry, Hematology and Urinalysis Parameters.   [ Time Frame: Day -1 to Day 8 ]

Measure Type Secondary
Measure Title Number of Participants With Changes From Baseline in Serum Chemistry, Hematology and Urinalysis Parameters.
Measure Description Hematology, serum chemistry, and urinalysis, including prothrombin time, international normalized ratio, partial thromboplastin time, and activated partial thromboplastin time, were completed at Screening, Day -1, Day 3 (48 hours postdose), and Day 8 (168 hours postdose)/ET.
Time Frame Day -1 to Day 8  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The abnormal values of laboratory values in participants are captured as serious AEs/AEs and are reported in the SAE or other AE section of this results report.

Reporting Groups
  Description
Mild Hepatic Impairment Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Moderate Hepatic Impairment Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Severe Hepatic Impairment Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Participants with normal hepatic function (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

Measured Values
   Mild Hepatic Impairment   Moderate Hepatic Impairment   Severe Hepatic Impairment   Normal Hepatic Function 
Participants Analyzed   8   8   6   23 
Number of Participants With Changes From Baseline in Serum Chemistry, Hematology and Urinalysis Parameters. 
[Units: Participant]
 0   0   0   0 

No statistical analysis provided for Number of Participants With Changes From Baseline in Serum Chemistry, Hematology and Urinalysis Parameters.



27.  Secondary:   Incidence of Suicidality, Suicidal Behaviour or Suicidal Ideation as Measured by the Columbia-Suicide Severity Rating Scale (C-SSRS)   [ Time Frame: Day 1, Day 4, Day 7 ]

Measure Type Secondary
Measure Title Incidence of Suicidality, Suicidal Behaviour or Suicidal Ideation as Measured by the Columbia-Suicide Severity Rating Scale (C-SSRS)
Measure Description The Baseline version of the C-SSRS was administered at Screening. The Since Last Visit version of the C-SSRS was administered on Day 1 at predose and on Days 4 and 7.
Time Frame Day 1, Day 4, Day 7  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Suicidality, suicidal behaviour or suicidal ideation are captured as serious AEs/AEs and are reported in the SAE or other AE section of this results report.

Reporting Groups
  Description
Mild Hepatic Impairment Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Moderate Hepatic Impairment Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Severe Hepatic Impairment Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Participants with normal hepatic function (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

Measured Values
   Mild Hepatic Impairment   Moderate Hepatic Impairment   Severe Hepatic Impairment   Normal Hepatic Function 
Participants Analyzed   8   8   6   23 
Incidence of Suicidality, Suicidal Behaviour or Suicidal Ideation as Measured by the Columbia-Suicide Severity Rating Scale (C-SSRS) 
[Units: Participants]
 0   0   0   0 

No statistical analysis provided for Incidence of Suicidality, Suicidal Behaviour or Suicidal Ideation as Measured by the Columbia-Suicide Severity Rating Scale (C-SSRS)




  Serious Adverse Events


  Other Adverse Events

Time Frame Adverse events were recorded from the time the Informed Consent Form was signed, throughout the 8 day study up to 30 days after study drug administration.
Additional Description The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.

Frequency Threshold
Threshold above which other adverse events are reported   0%  

Reporting Groups
  Description
Mild Hepatic Impairment Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Moderate Hepatic Impairment Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Severe Hepatic Impairment Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Normal Hepatic Function Participants with normal hepatic function (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

Other Adverse Events
    Mild Hepatic Impairment   Moderate Hepatic Impairment   Severe Hepatic Impairment   Normal Hepatic Function
Total, Other (not including serious) Adverse Events         
# participants affected / at risk   3/8 (37.50%)   3/8 (37.50%)   1/6 (16.67%)   6/23 (26.09%) 
Gastrointestinal disorders         
Diarrhoea * 1         
# participants affected / at risk   0/8 (0.00%)   1/8 (12.50%)   0/6 (0.00%)   0/23 (0.00%) 
General disorders         
Fatigue * 1         
# participants affected / at risk   1/8 (12.50%)   1/8 (12.50%)   0/6 (0.00%)   0/23 (0.00%) 
Musculoskeletal and connective tissue disorders         
Musculoskeletal pain * 1         
# participants affected / at risk   0/8 (0.00%)   0/8 (0.00%)   0/6 (0.00%)   1/23 (4.35%) 
Nervous system disorders         
Dizziness * 1         
# participants affected / at risk   1/8 (12.50%)   0/8 (0.00%)   0/6 (0.00%)   0/23 (0.00%) 
Headache * 1         
# participants affected / at risk   1/8 (12.50%)   1/8 (12.50%)   1/6 (16.67%)   4/23 (17.39%) 
Somnolence * 1         
# participants affected / at risk   0/8 (0.00%)   1/8 (12.50%)   0/6 (0.00%)   1/23 (4.35%) 
Respiratory, thoracic and mediastinal disorders         
Cough * 1         
# participants affected / at risk   0/8 (0.00%)   1/8 (12.50%)   0/6 (0.00%)   0/23 (0.00%) 
* Events were collected by non-systematic assessment
1 Term from vocabulary, MedDRA



  Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Global Medical Affairs
Organization: Otsuka Pharmaceutical Development and Commercialization, Inc.
phone: 800-562-3974



Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier: NCT01299454     History of Changes
Other Study ID Numbers: 331-09-225
First Submitted: February 16, 2011
First Posted: February 18, 2011
Results First Submitted: August 4, 2015
Results First Posted: September 3, 2015
Last Update Posted: October 20, 2015