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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
Enrollment 45
Recruitment Details 81 participants were screened; of these 45 participants were enrolled recruited at 3 study sites in the United States (US).
Pre-assignment Details  
Arm/Group Title Mild Hepatic Impairment Moderate Hepatic Impairment Severe Hepatic Impairment Normal Hepatic Function
Hide Arm/Group Description Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 milligrams (mg). Participants with moderate hepatic impairment (Child-Pugh classification scheme)received a single dose of oral brexpiprazole 2 mg. Participants with severe hepatic impairment (based on Child-Pugh classification scheme) received a single dose of oral brexpiprazole 2 mg. Participants with normal hepatic function (based on Child-Pugh classification scheme) received a single dose of oral brexpiprazole 2 mg.
Period Title: Overall Study
Started 8 8 6 23
Completed 8 8 6 23
Not Completed 0 0 0 0
Arm/Group Title Mild Hepatic Impairment Moderate Hepatic Impairment Severe Hepatic Impairment Normal Hepatic Function Total
Hide Arm/Group Description Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. Participants with normal hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. Total of all reporting groups
Overall Number of Baseline Participants 8 8 6 23 45
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 8 participants 8 participants 6 participants 23 participants 45 participants
59.5  (7.3) 57.8  (3.8) 51.2  (4.4) 56.2  (5.2) 56.4  (5.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 8 participants 6 participants 23 participants 45 participants
Female
3
  37.5%
2
  25.0%
0
   0.0%
5
  21.7%
10
  22.2%
Male
5
  62.5%
6
  75.0%
6
 100.0%
18
  78.3%
35
  77.8%
1.Primary Outcome
Title Unbound Brexpiprazole Area Under the Concentration Time Curve (AUC) Calculated to the Last Observable Concentration at Time t (AUCt,u)
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetics (PK) set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations.
Arm/Group Title 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.
Hide Arm/Group Description:
Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

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.

Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

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.

Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

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.

Overall Number of Participants Analyzed 8 8 8 8 6 6
Mean (Standard Deviation)
Unit of Measure: nanograms.hours/mL (ng*h/mL)
5.95  (2.58) 4.87  (1.78) 5.41  (1.37) 4.28  (1.95) 3.27  (0.93) 3.63  (1.54)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mild Hepatic Impairment, Normal Hepatic Function Matched to Mild Hepatic Function
Comments 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.
Type of Statistical Test Non-Inferiority or Equivalence
Comments 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.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed effect analysis of variance
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 1.166
Confidence Interval (2-Sided) 90%
0.776 to 1.751
Estimation Comments 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.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Moderate Hepatic Impairment, Normal Hepatic Function Matched to Moderate Hepatic Function.
Comments 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.
Type of Statistical Test Non-Inferiority or Equivalence
Comments 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.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed effect analysis of variance
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 1.375
Confidence Interval (2-Sided) 90%
0.915 to 2.066
Estimation Comments 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.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Severe Hepatic Impairment, Normal Hepatic Function Matched to Severe Hepatic Function.
Comments 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.
Type of Statistical Test Non-Inferiority or Equivalence
Comments 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.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed effect analysis of variance
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 0.929
Confidence Interval (2-Sided) 90%
0.581 to 1.488
Estimation Comments 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 Outcome
Title Unbound Brexpiprazole AUC Calculated From Time Zero to Infinity (AUC∞,u)
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations.
Arm/Group Title 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.
Hide Arm/Group Description:
Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg

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.

Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

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.

Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

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

Overall Number of Participants Analyzed 7 6 7 7 3 5
Mean (Standard Deviation)
Unit of Measure: ng*h/mL
8.59  (5.29) 5.85  (3.11) 8.50  (2.17) 5.62  (3.13) 3.49  (0.848) 3.36  (0.871)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mild Hepatic Impairment, Normal Hepatic Function Matched to Mild Hepatic Function.
Comments 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.
Type of Statistical Test Non-Inferiority or Equivalence
Comments 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.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed effect analysis of variance
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometic Mean Ratio
Estimated Value 1.255
Confidence Interval (2-Sided) 90%
0.702 to 2.244
Estimation Comments 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.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Moderate Hepatic Impairment., Normal Hepatic Function Matched to Moderate Hepatic Function.
Comments 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.
Type of Statistical Test Non-Inferiority or Equivalence
Comments 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.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed effect analysis of variance
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 1.727
Confidence Interval (2-Sided) 90%
0.977 to 3.052
Estimation Comments 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.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Severe Hepatic Function, Normal Hepatic Function Matched to Severe Hepatic Function.
Comments 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
Type of Statistical Test Non-Inferiority or Equivalence
Comments 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.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed effect analysis of variance
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometic Mean Ratio
Estimated Value 1.041
Confidence Interval (2-Sided) 90%
0.506 to 2.142
Estimation Comments 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 Outcome
Title Unbound Maximum Plasma Concentration of Brexpiprazole (Cmax,u)
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations.
Arm/Group Title 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.
Hide Arm/Group Description:
Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

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.

Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

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.

Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

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

Overall Number of Participants Analyzed 8 8 8 8 6 6
Mean (Standard Deviation)
Unit of Measure: ng/mL
0.104  (0.0259) 0.114  (0.0270) 0.0648  (0.0143) 0.0779  (0.0224) 0.0392  (0.0105) 0.0760  (0.0258)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mild Hepatic Impairment, Normal Hepatic Function Matched to Mild Hepatic Function.
Comments 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
Type of Statistical Test Non-Inferiority or Equivalence
Comments 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.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed effect analysis of variance
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 0.904
Confidence Interval (2-Sided) 90%
0.707 to 1.156
Estimation Comments 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.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Moderate Hepatic Impairment, Normal Hepatic Function Matched to Moderate Hepatic Function.
Comments 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
Type of Statistical Test Non-Inferiority or Equivalence
Comments 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.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed effect analysis of variance
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 0.850
Confidence Interval (2-Sided) 90%
0.665 to 1.087
Estimation Comments 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.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Severe Hepatic Impairment, Normal Hepatic Function Matched to Severe Hepatic Function.
Comments 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
Type of Statistical Test Non-Inferiority or Equivalence
Comments 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.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed effect analysis of variance
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 0.531
Confidence Interval 90%
0.399 to 0.705
Estimation Comments 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 Outcome
Title Area Under the Curve of Brexpiprazole Calculated to the Last Observable Concentration at Time t (AUCt)
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations.
Arm/Group Title 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.
Hide Arm/Group Description:
Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

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.

Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

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.

Participants with normal hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

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.

Overall Number of Participants Analyzed 8 8 8 8 6 6
Mean (Standard Deviation)
Unit of Measure: ng*h/mL
1271  (569) 1145  (539) 1213  (405) 1048  (422) 622  (163) 817  (306)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mild Hepatic Impairment, Normal Hepatic Function Matched to Mild Hepatic Function.
Comments 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.
Type of Statistical Test Non-Inferiority or Equivalence
Comments 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.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed effect analysis of variance
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 1.103
Confidence Interval (2-Sided) 90%
0.774 to 1.573
Estimation Comments 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.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Moderate Hepatic Impairment, Normal Hepatic Function Matched to Moderate Hepatic Function.
Comments 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.
Type of Statistical Test Non-Inferiority or Equivalence
Comments 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.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed effect analysis of variance
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 1.199
Confidence Interval (2-Sided) 90%
0.841 to 1.710
Estimation Comments 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.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Severe Hepatic Impairment, Normal Hepatic Function Matched to Severe Hepatic Function.
Comments 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.
Type of Statistical Test Non-Inferiority or Equivalence
Comments 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.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed effect analysis of variance
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 0.790
Confidence Interval (2-Sided) 90%
0.524 to 1.189
Estimation Comments 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 Outcome
Title Area Under the Concentration Time Curve of Brexpiprazole From Time Zero to Infinity (AUC∞)
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations.
Arm/Group Title 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.
Hide Arm/Group Description:
Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

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.

Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

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.

Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

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.

Overall Number of Participants Analyzed 7 6 7 7 3 5
Mean (Standard Deviation)
Unit of Measure: ng*h/mL
1827  (1103) 1393  (881) 1960  (579) 1345  (697) 831  (234) 788  (230)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mild Hepatic Impairment, Normal Hepatic Function Matched to Mild Hepatic Function.
Comments 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.
Type of Statistical Test Non-Inferiority or Equivalence
Comments 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.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed effect analysis of variance
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 1.241
Confidence Interval (2-Sided) 90%
0.719 to 2.143
Estimation Comments 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.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Moderate Hepatic Impairment, Normal Hepatic Function Matched to Moderate Hepatic Function.
Comments 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.
Type of Statistical Test Non-Inferiority or Equivalence
Comments 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
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed effect analysis of variance
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 1.604
Confidence Interval (2-Sided) 90%
0.942 to 2.732
Estimation Comments 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.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Severe Hepatic Impairment, Normal Hepatic Function Matched to Severe Hepatic Function.
Comments 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.
Type of Statistical Test Non-Inferiority or Equivalence
Comments 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.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed effect analysis of variance
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 1.077
Confidence Interval (2-Sided) 90%
0.540 to 2.146
Estimation Comments 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 Outcome
Title Maximum Plasma Concentration of Brexpiprazole (Cmax)
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations.
Arm/Group Title 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.
Hide Arm/Group Description:
Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

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.

Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

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.

Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

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.

Overall Number of Participants Analyzed 8 8 8 8 6 6
Mean (Standard Deviation)
Unit of Measure: ng/mL
22.9  (7.60) 26.7  (9.09) 14.6  (4.63) 19.3  (4.98) 7.65  (2.69) 17.7  (7.38)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mild Hepatic Impairment, Normal Hepatic Function Matched to Mild Hepatic Function.
Comments 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.
Type of Statistical Test Non-Inferiority or Equivalence
Comments 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.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed effect analysis of variance
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 0.856
Confidence Interval (2-Sided) 90%
0.691 to 1.059
Estimation Comments 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.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Moderate Hepatic Impairment, Normal Hepatic Function Matched to Moderate Hepatic Function.
Comments 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.
Type of Statistical Test Non-Inferiority or Equivalence
Comments 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.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed effect analysis of variance
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 0.742
Confidence Interval (2-Sided) 90%
0.599 to 0.918
Estimation Comments 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.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Severe Hepatic Impairment, Normal Hepatic Function Matched to Severe Hepatic Function.
Comments 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.
Type of Statistical Test Non-Inferiority or Equivalence
Comments 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.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed effect analysis of variance
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 0.451
Confidence Interval (2-Sided) 90%
0.352 to 0.577
Estimation Comments 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 Outcome
Title Time to Cmax of Brexiprazole (Tmax)
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations.
Arm/Group Title 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.
Hide Arm/Group Description:
Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

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.

Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

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.

Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

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.

Overall Number of Participants Analyzed 8 8 8 8 6 6
Median (Full Range)
Unit of Measure: h
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)
8.Secondary Outcome
Title Apparent Clearance of Brexpiprazole From Plasma After Extravascular Administration (CL/F)
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations.
Arm/Group Title 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.
Hide Arm/Group Description:
Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

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.

Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

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.

Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

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.

Overall Number of Participants Analyzed 7 6 7 6 3 5
Mean (Standard Deviation)
Unit of Measure: mL/h/kg
24.5  (28.2) 25.4  (12.3) 13.8  (2.72) 26.0  (19.2) 28.2  (6.70) 34.2  (16.3)
9.Secondary Outcome
Title Unbound Fraction of Brexpiprazole in Plasma (fu)
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations.
Arm/Group Title 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.
Hide Arm/Group Description:
Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

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.

Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

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.

Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

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.

Overall Number of Participants Analyzed 8 8 8 8 6 6
Mean (Standard Deviation)
Unit of Measure: % unbound drug in the urine
0.472  (0.0840) 0.451  (0.112) 0.462  (0.0786) 0.400  (0.0442) 0.544  (0.186) 0.450  (0.0795)
10.Secondary Outcome
Title Apparent Unbound Clearance of Brexpiprazole From Plasma After Extravascular Administration (CLu/F)
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations.
Arm/Group Title 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.
Hide Arm/Group Description:
Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

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.

Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

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

Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

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

Overall Number of Participants Analyzed 7 6 7 7 3 5
Mean (Standard Deviation)
Unit of Measure: mL/h/kg
5674  (7165) 5730  (2944) 3115  (494) 6768  (5833) 6598  (1182) 7697  (2653)
11.Secondary Outcome
Title Terminal-phase Elimination Half-life of Brexpiprazole (t1/2,z)
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations.
Arm/Group Title 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.
Hide Arm/Group Description:
Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

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.

Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

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.

Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

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

Overall Number of Participants Analyzed 7 6 7 7 3 5
Mean (Standard Deviation)
Unit of Measure: h
103  (51.1) 64.7  (24.6) 116  (25.8) 64.2  (26.2) 81.1  (17.1) 51.4  (8.21)
12.Secondary Outcome
Title Renal Clearance (CLr) of Brexipiprazole
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations.
Arm/Group Title 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.
Hide Arm/Group Description:
Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

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.

Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

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.

Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

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.

Overall Number of Participants Analyzed 8 8 8 8 6 6
Mean (Standard Deviation)
Unit of Measure: mL/h/kg
0.0468  (0.0353) 0.0263  (0.0244) 0.0360  (0.0286) 0.0422  (0.0383) 0.0402  (0.0872) 0.0193  (0.0203)
13.Secondary Outcome
Title Cumulative Amount of Brexpiprazole Excreted Into the Urine (Ae,u)
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations.
Arm/Group Title 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.
Hide Arm/Group Description:
Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

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.

Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

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.

Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

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.

Overall Number of Participants Analyzed 8 8 8 8 6 6
Mean (Standard Deviation)
Unit of Measure: ng
4511  (3808) 1854  (1500) 3522  (2740) 3837  (3358) 2090  (4699) 1326  (1427)
14.Secondary Outcome
Title Fraction of Systemically Available Brexpiprazole Excreted Into the Urine (fe,u)
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations.
Arm/Group Title 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.
Hide Arm/Group Description:
Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

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.

Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

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.

Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

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.

Overall Number of Participants Analyzed 8 8 8 8 6 6
Mean (Standard Deviation)
Unit of Measure: % of drug in urine
0.226  (0.190) 0.0927  (0.0750) 0.176  (0.137) 0.192  (0.168) 0.104  (0.235) 0.0663  (0.0713)
15.Secondary Outcome
Title AUCt for DM-3411 Metabolite
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations.
Arm/Group Title 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.
Hide Arm/Group Description:
Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

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.

Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

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.

Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

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.

Overall Number of Participants Analyzed 8 8 8 8 6 6
Mean (Standard Deviation)
Unit of Measure: ng*h/mL
380  (195) 683  (246) 284  (164) 486  (263) 151  (51.4) 479  (226)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mild Hepatic Impairment, Normal Hepatic Function Matched to Mild Hepatic Function.
Comments 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.
Type of Statistical Test Non-Inferiority or Equivalence
Comments 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.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed effect analysis of variance
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 0.509
Confidence Interval (2-Sided) 90%
0.346 to 0.748
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Moderate Hepatic Impairment, Normal Hepatic Function Matched to Moderate Hepatic Function.
Comments 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.
Type of Statistical Test Non-Inferiority or Equivalence
Comments 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.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed effect analysis of variance
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 0.586
Confidence Interval (2-Sided) 90%
0.399 to 0.861
Estimation Comments 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.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Severe Hepatic Impairment, Normal Hepatic Function Matched to Severe Hepatic Function.
Comments 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.
Type of Statistical Test Non-Inferiority or Equivalence
Comments 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.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed effect analysis of variance
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 0.334
Confidence Interval (2-Sided) 90%
0.214 to 0.521
Estimation Comments 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 Outcome
Title AUC∞ for DM-3411 Metabolite
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations.
Arm/Group Title 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.
Hide Arm/Group Description:
Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

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.

Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

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.

Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

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.

Overall Number of Participants Analyzed 5 6 6 6 4 3
Mean (Standard Deviation)
Unit of Measure: ng*h/mL
489  (210) 692  (259) 382  (262) 530  (211) 187  (67.2) 329  (167)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mild Hepatic Impairment, Normal Hepatic Function Matched to Mild Hepatic Function.
Comments 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.
Type of Statistical Test Non-Inferiority or Equivalence
Comments 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.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed effect analysis of variance
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 0.716
Confidence Interval (2-Sided) 90%
0.445 to 1.153
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Moderate Hepatic Impairment, Normal Hepatic Function Matched to Moderate Hepatic Function.
Comments 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.
Type of Statistical Test Non-Inferiority or Equivalence
Comments 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.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed effect analysis of variance
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 0.594
Confidence Interval (2-Sided) 90%
0.378 to 0.934
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Severe Hepatic Impairment, Normal Hepatic Function Matched to Severe Hepatic Function.
Comments 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.
Type of Statistical Test Non-Inferiority or Equivalence
Comments 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.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed effect analysis of variance
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 0.561
Confidence Interval (2-Sided) 90%
0.308 to 1.022
Estimation Comments [Not Specified]
17.Secondary Outcome
Title Cmax for DM-3411 Metabolite
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations.
Arm/Group Title 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.
Hide Arm/Group Description:
Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

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.

Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

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

Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

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.

Overall Number of Participants Analyzed 8 8 8 8 6 6
Mean (Standard Deviation)
Unit of Measure: ng/mL
6.49  (5.13) 10.5  (4.26) 3.19  (1.56) 7.25  (4.83) 2.15  (0.880) 7.13  (3.73)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mild Hepatic Impairment, Normal Hepatic Function Matched to Mild Hepatic Function.
Comments 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.
Type of Statistical Test Non-Inferiority or Equivalence
Comments 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.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed effect analysis of variance
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 0.558
Confidence Interval (2-Sided) 90%
0.368 to 0.845
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Moderate Hepatic Impairment, Normal Hepatic Function Matched to Moderate Hepatic Function.
Comments 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.
Type of Statistical Test Non-Inferiority or Equivalence
Comments 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.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed effect analysis of variance
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 0.516
Confidence Interval (2-Sided) 90%
0.341 to 0.781
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Severe Hepatic Impairment, Normal Hepatic Function Matched to Severe Hepatic Function.
Comments 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.
Type of Statistical Test Non-Inferiority or Equivalence
Comments 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.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed effect analysis of variance
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 0.314
Confidence Interval (2-Sided) 90%
0.195 to 0.507
Estimation Comments [Not Specified]
18.Secondary Outcome
Title Tmax for DM-3411 Metabolite
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations.
Arm/Group Title 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.
Hide Arm/Group Description:
Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

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.

Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

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.

Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

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.

Overall Number of Participants Analyzed 8 8 8 8 6 6
Median (Full Range)
Unit of Measure: h
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)
19.Secondary Outcome
Title t1/2,z for DM-3411 Metabolite
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations.
Arm/Group Title 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.
Hide Arm/Group Description:
Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

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.

Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

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.

Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

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.

Overall Number of Participants Analyzed 5 6 6 6 4 3
Mean (Standard Deviation)
Unit of Measure: h
78.8  (37.6) 59.7  (15.7) 87.2  (45.7) 62.0  (26.4) 84.6  (12.0) 56.1  (8.25)
20.Secondary Outcome
Title Ae,u for DM-3411 Metabolite
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations.
Arm/Group Title 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.
Hide Arm/Group Description:
Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

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.

Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

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

Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

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.

Overall Number of Participants Analyzed 8 8 8 8 6 6
Mean (Standard Deviation)
Unit of Measure: ng
67086  (25276) 81148  (23188) 68413  (16993) 71353  (41630) 48190  (14756) 83604  (34907)
21.Secondary Outcome
Title fe,u for DM-3411 Metabolite
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations.
Arm/Group Title 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.
Hide Arm/Group Description:
Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

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.

Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg

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.

Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

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.

Overall Number of Participants Analyzed 8 8 8 8 6 6
Mean (Standard Deviation)
Unit of Measure: % metabolite excreted in urine
3.23  (1.22) 3.91  (1.12) 3.30  (0.819) 3.44  (2.01) 2.32  (0.712) 4.03  (1.68)
22.Secondary Outcome
Title CLr for DM-3411 Metabolite
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations.
Arm/Group Title 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.
Hide Arm/Group Description:
Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

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.

Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

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.

Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.

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.

Overall Number of Participants Analyzed 8 8 8 8 6 6
Mean (Standard Deviation)
Unit of Measure: mL/h/kg
2.67  (1.31) 1.83  (0.828) 3.96  (2.32) 1.90  (0.568) 4.08  (1.68) 2.33  (1.01)
23.Secondary Outcome
Title Number of Adverse Events (AEs) Reported
Hide 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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one dose of study drug were included in the safety analysis.
Arm/Group Title Mild Hepatic Impairment Moderate Hepatic Impairment Severe Hepatic Impairment Normal Hepatic Function
Hide Arm/Group Description:
Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Participants with normal hepatic function (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Overall Number of Participants Analyzed 8 8 6 23
Measure Type: Number
Unit of Measure: Events
Adverse events 3 5 1 8
Treatment emergent adverse events 3 5 1 6
Serious adverse events 0 0 0 0
24.Secondary Outcome
Title Number of Participants With Changes From Baseline in Vital Signs Parameters.
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Mild Hepatic Impairment Moderate Hepatic Impairment Severe Hepatic Impairment Normal Hepatic Function
Hide Arm/Group Description:
Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Participants with normal hepatic function (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Overall Number of Participants Analyzed 8 8 6 23
Measure Type: Number
Unit of Measure: Participants
0 0 0 0
25.Secondary Outcome
Title Number of Participants With Changes From Baseline in Electrocardiogram (ECG) Parameters.
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Mild Hepatic Impairment Moderate Hepatic Impairment Severe Hepatic Impairment Normal Hepatic Function
Hide Arm/Group Description:
Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Participants with normal hepatic function (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Overall Number of Participants Analyzed 8 8 6 23
Measure Type: Number
Unit of Measure: Participants
0 0 0 0
26.Secondary Outcome
Title Number of Participants With Changes From Baseline in Serum Chemistry, Hematology and Urinalysis Parameters.
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Mild Hepatic Impairment Moderate Hepatic Impairment Severe Hepatic Impairment Normal Hepatic Function
Hide Arm/Group Description:
Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Participants with normal hepatic function (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Overall Number of Participants Analyzed 8 8 6 23
Measure Type: Number
Unit of Measure: Participant
0 0 0 0
27.Secondary Outcome
Title Incidence of Suicidality, Suicidal Behaviour or Suicidal Ideation as Measured by the Columbia-Suicide Severity Rating Scale (C-SSRS)
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Mild Hepatic Impairment Moderate Hepatic Impairment Severe Hepatic Impairment Normal Hepatic Function
Hide Arm/Group Description:
Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Participants with normal hepatic function (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Overall Number of Participants Analyzed 8 8 6 23
Measure Type: Number
Unit of Measure: Participants
0 0 0 0
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.
Adverse Event Reporting 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.
 
Arm/Group Title Mild Hepatic Impairment Moderate Hepatic Impairment Severe Hepatic Impairment Normal Hepatic Function
Hide Arm/Group Description Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. Participants with normal hepatic function (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
All-Cause Mortality
Mild Hepatic Impairment Moderate Hepatic Impairment Severe Hepatic Impairment Normal Hepatic Function
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Mild Hepatic Impairment Moderate Hepatic Impairment Severe Hepatic Impairment Normal Hepatic Function
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/8 (0.00%)   0/8 (0.00%)   0/6 (0.00%)   0/23 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Mild Hepatic Impairment Moderate Hepatic Impairment Severe Hepatic Impairment Normal Hepatic Function
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   3/8 (37.50%)   3/8 (37.50%)   1/6 (16.67%)   6/23 (26.09%) 
Gastrointestinal disorders         
Diarrhoea * 1  0/8 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/23 (0.00%) 
General disorders         
Fatigue * 1  1/8 (12.50%)  1/8 (12.50%)  0/6 (0.00%)  0/23 (0.00%) 
Musculoskeletal and connective tissue disorders         
Musculoskeletal pain * 1  0/8 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  1/23 (4.35%) 
Nervous system disorders         
Dizziness * 1  1/8 (12.50%)  0/8 (0.00%)  0/6 (0.00%)  0/23 (0.00%) 
Headache * 1  1/8 (12.50%)  1/8 (12.50%)  1/6 (16.67%)  4/23 (17.39%) 
Somnolence * 1  0/8 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  1/23 (4.35%) 
Respiratory, thoracic and mediastinal disorders         
Cough * 1  0/8 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/23 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA
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