A Study Evaluating the of OPC34712 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

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Study Type:  Interventional 

Study Design:  Allocation: NonRandomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment 
Condition: 
Schizophrenia 
Intervention: 
Drug: OPC34712 
Participant Flow
Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations 

81 participants were screened; of these 45 participants were enrolled recruited at 3 study sites in the United States (US). 
PreAssignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment 

No text entered. 
Reporting Groups
Description  

Mild Hepatic Impairment  Participants with mild hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 milligrams (mg). 
Moderate Hepatic Impairment  Participants with moderate hepatic impairment (ChildPugh classification scheme)received a single dose of oral brexpiprazole 2 mg. 
Severe Hepatic Impairment  Participants with severe hepatic impairment (based on ChildPugh classification scheme) received a single dose of oral brexpiprazole 2 mg. 
Normal Hepatic Function  Participants with normal hepatic function (based on ChildPugh classification scheme) received a single dose of oral brexpiprazole 2 mg. 
Participant Flow: Overall Study
Mild Hepatic Impairment  Moderate Hepatic Impairment  Severe Hepatic Impairment  Normal Hepatic Function  

STARTED  8  8  6  23 
COMPLETED  8  8  6  23 
NOT COMPLETED  0  0  0  0 
Baseline Characteristics
Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. 

No text entered. 
Reporting Groups
Description  

Mild Hepatic Impairment  Participants with mild hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Moderate Hepatic Impairment  Participants with moderate hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Severe Hepatic Impairment  Participants with severe hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function  Participants with normal hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Total  Total of all reporting groups 
Baseline Measures
Mild Hepatic Impairment  Moderate Hepatic Impairment  Severe Hepatic Impairment  Normal Hepatic Function  Total  

Overall Participants Analyzed [Units: Participants] 
8  8  6  23  45  
Age [Units: Years] Mean (Standard Deviation) 
59.5 (7.3)  57.8 (3.8)  51.2 (4.4)  56.2 (5.2)  56.4 (5.7)  
Gender [Units: Participants] 

Female  3  2  0  5  10  
Male  5  6  6  18  35  
Outcome Measures
1. Primary:  Unbound Brexpiprazole Area Under the Concentration Time Curve (AUC) Calculated to the Last Observable Concentration at Time t (AUCt,u) [ Time Frame: Day 1 to Day 8 ] 
Measure Type  Primary 

Measure Title  Unbound Brexpiprazole Area Under the Concentration Time Curve (AUC) Calculated to the Last Observable Concentration at Time t (AUCt,u) 
Measure Description  Blood samples were taken at predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose/Early termination (ET). 
Time Frame  Day 1 to Day 8 
Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. 

Pharmacokinetics (PK) set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations. 
Reporting Groups
Description  

Mild Hepatic Impairment  Participants with mild hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function Matched to Mild Hepatic Function 
Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each participant with normal hepatic function was matched to a participant with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. 
Moderate Hepatic Impairment  Participants with moderate hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function Matched to Moderate Hepatic Function. 
Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each participant with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. 
Severe Hepatic Impairment  Participants with severe hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function Matched to Severe Hepatic Function. 
Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each participant with normal hepatic function was matched to a participant with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. 
Measured Values
Mild Hepatic Impairment  Normal Hepatic Function Matched to Mild Hepatic Function  Moderate Hepatic Impairment  Normal Hepatic Function Matched to Moderate Hepatic Function.  Severe Hepatic Impairment  Normal Hepatic Function Matched to Severe Hepatic Function.  

Participants Analyzed  8  8  8  8  6  6 
Unbound Brexpiprazole Area Under the Concentration Time Curve (AUC) Calculated to the Last Observable Concentration at Time t (AUCt,u) [Units: nanograms.hours/mL (ng*h/mL)] Mean (Standard Deviation) 
5.95 (2.58)  4.87 (1.78)  5.41 (1.37)  4.28 (1.95)  3.27 (0.93)  3.63 (1.54) 
Statistical Analysis 1 for Unbound Brexpiprazole Area Under the Concentration Time Curve (AUC) Calculated to the Last Observable Concentration at Time t (AUCt,u)
Groups ^{[1]}  Mild Hepatic Impairment vs. Normal Hepatic Function Matched to Mild Hepatic Function 

Statistical Test Type ^{[2]}  NonInferiority or Equivalence 
Statistical Method ^{[3]}  Mixed effect analysis of variance 
Geometric Mean Ratio ^{[4]}  1.166 
90% Confidence Interval  0.776 to 1.751 
[1]  Additional details about the analysis, such as null hypothesis and power calculation: 

The primary comparison was each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the primary PK parameters between each hepatic disease group and the control group, the 90% confidence interval (CI) for the difference in the means of the logtransformed data was calculated using a mixed effect analysis of variance.  
[2]  Details of power calculation, definition of noninferiority margin, and other key parameters: 
Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normaltheory CIs, this approach was equivalent to carrying out two 1sided tests of hypothesis at the 5% level of significance.  
[3]  Other relevant method information, such as adjustments or degrees of freedom: 
No text entered.  
[4]  Other relevant estimation information: 
Due to the nature of the normaltheory CIs, this approach is equivalent to carrying out two 1sided tests of hypothesis at the 5% level of significance. 
Statistical Analysis 2 for Unbound Brexpiprazole Area Under the Concentration Time Curve (AUC) Calculated to the Last Observable Concentration at Time t (AUCt,u)
Groups ^{[1]}  Moderate Hepatic Impairment vs. Normal Hepatic Function Matched to Moderate Hepatic Function. 

Statistical Test Type ^{[2]}  NonInferiority or Equivalence 
Statistical Method ^{[3]}  Mixed effect analysis of variance 
Geometric Mean Ratio ^{[4]}  1.375 
90% Confidence Interval  0.915 to 2.066 
[1]  Additional details about the analysis, such as null hypothesis and power calculation: 

The primary comparison was each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the primary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the logtransformed data was calculated using a mixed effect analysis of variance.  
[2]  Details of power calculation, definition of noninferiority margin, and other key parameters: 
Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normaltheory CIs, this approach was equivalent to carrying out two 1sided tests of hypothesis at the 5% level of significance.  
[3]  Other relevant method information, such as adjustments or degrees of freedom: 
No text entered.  
[4]  Other relevant estimation information: 
Due to the nature of the normaltheory CIs, this approach is equivalent to carrying out two 1sided tests of hypothesis at the 5% level of significance. 
Statistical Analysis 3 for Unbound Brexpiprazole Area Under the Concentration Time Curve (AUC) Calculated to the Last Observable Concentration at Time t (AUCt,u)
Groups ^{[1]}  Severe Hepatic Impairment vs. Normal Hepatic Function Matched to Severe Hepatic Function. 

Statistical Test Type ^{[2]}  NonInferiority or Equivalence 
Statistical Method ^{[3]}  Mixed effect analysis of variance 
Geometric Mean Ratio ^{[4]}  0.929 
90% Confidence Interval  0.581 to 1.488 
[1]  Additional details about the analysis, such as null hypothesis and power calculation: 

The primary comparison was each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the primary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the logtransformed data was calculated using a mixed effect analysis of variance.  
[2]  Details of power calculation, definition of noninferiority margin, and other key parameters: 
Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normaltheory CIs, this approach was equivalent to carrying out two 1sided tests of hypothesis at the 5% level of significance.  
[3]  Other relevant method information, such as adjustments or degrees of freedom: 
No text entered.  
[4]  Other relevant estimation information: 
Due to the nature of the normaltheory CIs, this approach is equivalent to carrying out two 1sided tests of hypothesis at the 5% level of significance. 
2. Primary:  Unbound Brexpiprazole AUC Calculated From Time Zero to Infinity (AUC∞,u) [ Time Frame: Day 1 to Day 8 ] 
Measure Type  Primary 

Measure Title  Unbound Brexpiprazole AUC Calculated From Time Zero to Infinity (AUC∞,u) 
Measure Description 
Blood samples were taken at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose/ET. AUC (0  ∞)= AUC from time zero (predose) to extrapolated infinite time (0  ∞). It is obtained from AUC (0  t) plus AUC (t  ∞). 
Time Frame  Day 1 to Day 8 
Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. 

PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations. 
Reporting Groups
Description  

Mild Hepatic Impairment  Participants with mild hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg 
Normal Hepatic Function Matched to Mild Hepatic Function. 
Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each participant with normal hepatic function was matched to a participant with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. 
Moderate Hepatic Impairment.  Participants with moderate hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function Matched to Moderate Hepatic Function. 
Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each participant with normal hepatic function was matched to a participant with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. 
Severe Hepatic Function  Participants with severe hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function Matched to Severe Hepatic Function. 
Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each participant with normal hepatic function was matched to a participant with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled 
Measured Values
Mild Hepatic Impairment  Normal Hepatic Function Matched to Mild Hepatic Function.  Moderate Hepatic Impairment.  Normal Hepatic Function Matched to Moderate Hepatic Function.  Severe Hepatic Function  Normal Hepatic Function Matched to Severe Hepatic Function.  

Participants Analyzed  7  6  7  7  3  5 
Unbound Brexpiprazole AUC Calculated From Time Zero to Infinity (AUC∞,u) [Units: ng*h/mL] Mean (Standard Deviation) 
8.59 (5.29)  5.85 (3.11)  8.50 (2.17)  5.62 (3.13)  3.49 (0.848)  3.36 (0.871) 
Statistical Analysis 1 for Unbound Brexpiprazole AUC Calculated From Time Zero to Infinity (AUC∞,u)
Groups ^{[1]}  Mild Hepatic Impairment vs. Normal Hepatic Function Matched to Mild Hepatic Function. 

Statistical Test Type ^{[2]}  NonInferiority or Equivalence 
Statistical Method ^{[3]}  Mixed effect analysis of variance 
Geometic Mean Ratio ^{[4]}  1.255 
90% Confidence Interval  0.702 to 2.244 
[1]  Additional details about the analysis, such as null hypothesis and power calculation: 

The primary comparison was each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the primary PK parameters between each hepatic disease group and the control group, the 90% confidence interval (CI) for the difference in the means of the logtransformed data was calculated using a mixed effect analysis of variance.  
[2]  Details of power calculation, definition of noninferiority margin, and other key parameters: 
Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normaltheory CIs, this approach was equivalent to carrying out two 1sided tests of hypothesis at the 5% level of significance.  
[3]  Other relevant method information, such as adjustments or degrees of freedom: 
No text entered.  
[4]  Other relevant estimation information: 
Due to the nature of the normaltheory CIs, this approach is equivalent to carrying out two 1sided tests of hypothesis at the 5% level of significance. 
Statistical Analysis 2 for Unbound Brexpiprazole AUC Calculated From Time Zero to Infinity (AUC∞,u)
Groups ^{[1]}  Moderate Hepatic Impairment. vs. Normal Hepatic Function Matched to Moderate Hepatic Function. 

Statistical Test Type ^{[2]}  NonInferiority or Equivalence 
Statistical Method ^{[3]}  Mixed effect analysis of variance 
Geometric Mean Ratio ^{[4]}  1.727 
90% Confidence Interval  0.977 to 3.052 
[1]  Additional details about the analysis, such as null hypothesis and power calculation: 

The primary comparison was each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the primary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the logtransformed data was calculated using a mixed effect analysis of variance.  
[2]  Details of power calculation, definition of noninferiority margin, and other key parameters: 
Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normaltheory CIs, this approach was equivalent to carrying out two 1sided tests of hypothesis at the 5% level of significance.  
[3]  Other relevant method information, such as adjustments or degrees of freedom: 
No text entered.  
[4]  Other relevant estimation information: 
Due to the nature of the normaltheory CIs, this approach is equivalent to carrying out two 1sided tests of hypothesis at the 5% level of significance. 
Statistical Analysis 3 for Unbound Brexpiprazole AUC Calculated From Time Zero to Infinity (AUC∞,u)
Groups ^{[1]}  Severe Hepatic Function vs. Normal Hepatic Function Matched to Severe Hepatic Function. 

Statistical Test Type ^{[2]}  NonInferiority or Equivalence 
Statistical Method ^{[3]}  Mixed effect analysis of variance 
Geometic Mean Ratio ^{[4]}  1.041 
90% Confidence Interval  0.506 to 2.142 
[1]  Additional details about the analysis, such as null hypothesis and power calculation: 

The primary comparison was each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the primary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the logtransformed data was calculated using a mixed effect analysis of variance  
[2]  Details of power calculation, definition of noninferiority margin, and other key parameters: 
Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normaltheory CIs, this approach was equivalent to carrying out two 1sided tests of hypothesis at the 5% level of significance.  
[3]  Other relevant method information, such as adjustments or degrees of freedom: 
No text entered.  
[4]  Other relevant estimation information: 
Due to the nature of the normaltheory CIs, this approach is equivalent to carrying out two 1sided tests of hypothesis at the 5% level of significance. 
3. Primary:  Unbound Maximum Plasma Concentration of Brexpiprazole (Cmax,u) [ Time Frame: Day 1 to Day 8 ] 
Measure Type  Primary 

Measure Title  Unbound Maximum Plasma Concentration of Brexpiprazole (Cmax,u) 
Measure Description 
Blood samples were taken at predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose/ET. Cmax,u is the highest measured unbound plasma concentration during the dosing interval. 
Time Frame  Day 1 to Day 8 
Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. 

PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations. 
Reporting Groups
Description  

Mild Hepatic Impairment  Participants with mild hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function Matched to Mild Hepatic Function. 
Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. 
Moderate Hepatic Impairment  Participants with moderate hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function Matched to Moderate Hepatic Function. 
Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. 
Severe Hepatic Impairment  Participants with severe hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function Matched to Severe Hepatic Function. 
Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled 
Measured Values
Mild Hepatic Impairment  Normal Hepatic Function Matched to Mild Hepatic Function.  Moderate Hepatic Impairment  Normal Hepatic Function Matched to Moderate Hepatic Function.  Severe Hepatic Impairment  Normal Hepatic Function Matched to Severe Hepatic Function.  

Participants Analyzed  8  8  8  8  6  6 
Unbound Maximum Plasma Concentration of Brexpiprazole (Cmax,u) [Units: ng/mL] Mean (Standard Deviation) 
0.104 (0.0259)  0.114 (0.0270)  0.0648 (0.0143)  0.0779 (0.0224)  0.0392 (0.0105)  0.0760 (0.0258) 
Statistical Analysis 1 for Unbound Maximum Plasma Concentration of Brexpiprazole (Cmax,u)
Groups ^{[1]}  Mild Hepatic Impairment vs. Normal Hepatic Function Matched to Mild Hepatic Function. 

Statistical Test Type ^{[2]}  NonInferiority or Equivalence 
Statistical Method ^{[3]}  Mixed effect analysis of variance 
Geometric Mean Ratio ^{[4]}  0.904 
90% Confidence Interval  0.707 to 1.156 
[1]  Additional details about the analysis, such as null hypothesis and power calculation: 

The primary comparison was each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the primary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the logtransformed data was calculated using a mixed effect analysis of variance  
[2]  Details of power calculation, definition of noninferiority margin, and other key parameters: 
Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normaltheory CIs, this approach was equivalent to carrying out two 1sided tests of hypothesis at the 5% level of significance.  
[3]  Other relevant method information, such as adjustments or degrees of freedom: 
No text entered.  
[4]  Other relevant estimation information: 
Due to the nature of the normaltheory CIs, this approach is equivalent to carrying out two 1sided tests of hypothesis at the 5% level of significance. 
Statistical Analysis 2 for Unbound Maximum Plasma Concentration of Brexpiprazole (Cmax,u)
Groups ^{[1]}  Moderate Hepatic Impairment vs. Normal Hepatic Function Matched to Moderate Hepatic Function. 

Statistical Test Type ^{[2]}  NonInferiority or Equivalence 
Statistical Method ^{[3]}  Mixed effect analysis of variance 
Geometric Mean Ratio ^{[4]}  0.850 
90% Confidence Interval  0.665 to 1.087 
[1]  Additional details about the analysis, such as null hypothesis and power calculation: 

The primary comparison was each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the primary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the logtransformed data was calculated using a mixed effect analysis of variance  
[2]  Details of power calculation, definition of noninferiority margin, and other key parameters: 
Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normaltheory CIs, this approach was equivalent to carrying out two 1sided tests of hypothesis at the 5% level of significance.  
[3]  Other relevant method information, such as adjustments or degrees of freedom: 
No text entered.  
[4]  Other relevant estimation information: 
Due to the nature of the normaltheory CIs, this approach is equivalent to carrying out two 1sided tests of hypothesis at the 5% level of significance. 
Statistical Analysis 3 for Unbound Maximum Plasma Concentration of Brexpiprazole (Cmax,u)
Groups ^{[1]}  Severe Hepatic Impairment vs. Normal Hepatic Function Matched to Severe Hepatic Function. 

Statistical Test Type ^{[2]}  NonInferiority or Equivalence 
Statistical Method ^{[3]}  Mixed effect analysis of variance 
Geometric Mean Ratio ^{[4]}  0.531 
90% Confidence Interval  0.399 to 0.705 
[1]  Additional details about the analysis, such as null hypothesis and power calculation: 

The primary comparison was each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the primary PK parameters between each hepatic disease group and the control group, the 90% confidence interval (CI) for the difference in the means of the logtransformed data was calculated using a mixed effect analysis of variance  
[2]  Details of power calculation, definition of noninferiority margin, and other key parameters: 
Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normaltheory CIs, this approach was equivalent to carrying out two 1sided tests of hypothesis at the 5% level of significance.  
[3]  Other relevant method information, such as adjustments or degrees of freedom: 
No text entered.  
[4]  Other relevant estimation information: 
Due to the nature of the normaltheory CIs, this approach is equivalent to carrying out two 1sided tests of hypothesis at the 5% level of significance. 
4. Secondary:  Area Under the Curve of Brexpiprazole Calculated to the Last Observable Concentration at Time t (AUCt) [ Time Frame: Day 1 to Day 8 ] 
Measure Type  Secondary 

Measure Title  Area Under the Curve of Brexpiprazole Calculated to the Last Observable Concentration at Time t (AUCt) 
Measure Description 
Blood samples were taken at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose/ET. AUCt= Area under the plasma concentration versus time curve from time zero (predose) to time of last quantifiable concentration (0t) The AUCt was estimated using the linear trapezoidal rule. 
Time Frame  Day 1 to Day 8 
Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. 

PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations. 
Reporting Groups
Description  

Mild Hepatic Impairment  Participants with mild hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function Matched to Mild Hepatic Function. 
Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each participant with normal hepatic function was matched to a participant with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. 
Moderate Hepatic Impairment  Participants with moderate hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function Matched to Moderate Hepatic Function. 
Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each participant with normal hepatic function was matched to a participant with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. 
Severe Hepatic Impairment  Participants with normal hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function Matched to Severe Hepatic Function. 
Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each participant with normal hepatic function was matched to a particpant with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. 
Measured Values
Mild Hepatic Impairment  Normal Hepatic Function Matched to Mild Hepatic Function.  Moderate Hepatic Impairment  Normal Hepatic Function Matched to Moderate Hepatic Function.  Severe Hepatic Impairment  Normal Hepatic Function Matched to Severe Hepatic Function.  

Participants Analyzed  8  8  8  8  6  6 
Area Under the Curve of Brexpiprazole Calculated to the Last Observable Concentration at Time t (AUCt) [Units: ng*h/mL] Mean (Standard Deviation) 
1271 (569)  1145 (539)  1213 (405)  1048 (422)  622 (163)  817 (306) 
Statistical Analysis 1 for Area Under the Curve of Brexpiprazole Calculated to the Last Observable Concentration at Time t (AUCt)
Groups ^{[1]}  Mild Hepatic Impairment vs. Normal Hepatic Function Matched to Mild Hepatic Function. 

Statistical Test Type ^{[2]}  NonInferiority or Equivalence 
Statistical Method ^{[3]}  Mixed effect analysis of variance 
Geometric Mean Ratio ^{[4]}  1.103 
90% Confidence Interval  0.774 to 1.573 
[1]  Additional details about the analysis, such as null hypothesis and power calculation: 

The secondary comparisons were each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the secondary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the logtransformed data was calculated using a mixed effect analysis of variance.  
[2]  Details of power calculation, definition of noninferiority margin, and other key parameters: 
Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normaltheory CIs, this approach was equivalent to carrying out two 1sided tests of hypothesis at the 5% level of significance.  
[3]  Other relevant method information, such as adjustments or degrees of freedom: 
No text entered.  
[4]  Other relevant estimation information: 
Due to the nature of the normaltheory CIs, this approach is equivalent to carrying out two 1sided tests of hypothesis at the 5% level of significance. 
Statistical Analysis 2 for Area Under the Curve of Brexpiprazole Calculated to the Last Observable Concentration at Time t (AUCt)
Groups ^{[1]}  Moderate Hepatic Impairment vs. Normal Hepatic Function Matched to Moderate Hepatic Function. 

Statistical Test Type ^{[2]}  NonInferiority or Equivalence 
Statistical Method ^{[3]}  Mixed effect analysis of variance 
Geometric Mean Ratio ^{[4]}  1.199 
90% Confidence Interval  0.841 to 1.710 
[1]  Additional details about the analysis, such as null hypothesis and power calculation: 

The secondary comparisons were each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the secondary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the logtransformed data was calculated using a mixed effect analysis of variance.  
[2]  Details of power calculation, definition of noninferiority margin, and other key parameters: 
Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normaltheory CIs, this approach was equivalent to carrying out two 1sided tests of hypothesis at the 5% level of significance.  
[3]  Other relevant method information, such as adjustments or degrees of freedom: 
No text entered.  
[4]  Other relevant estimation information: 
Due to the nature of the normaltheory CIs, this approach is equivalent to carrying out two 1sided tests of hypothesis at the 5% level of significance. 
Statistical Analysis 3 for Area Under the Curve of Brexpiprazole Calculated to the Last Observable Concentration at Time t (AUCt)
Groups ^{[1]}  Severe Hepatic Impairment vs. Normal Hepatic Function Matched to Severe Hepatic Function. 

Statistical Test Type ^{[2]}  NonInferiority or Equivalence 
Statistical Method ^{[3]}  Mixed effect analysis of variance 
Geometric Mean Ratio ^{[4]}  0.790 
90% Confidence Interval  0.524 to 1.189 
[1]  Additional details about the analysis, such as null hypothesis and power calculation: 

The secondary comparisons were each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the secondary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the logtransformed data was calculated using a mixed effect analysis of variance.  
[2]  Details of power calculation, definition of noninferiority margin, and other key parameters: 
Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normaltheory CIs, this approach was equivalent to carrying out two 1sided tests of hypothesis at the 5% level of significance.  
[3]  Other relevant method information, such as adjustments or degrees of freedom: 
No text entered.  
[4]  Other relevant estimation information: 
Due to the nature of the normaltheory CIs, this approach is equivalent to carrying out two 1sided tests of hypothesis at the 5% level of significance. 
5. Secondary:  Area Under the Concentration Time Curve of Brexpiprazole From Time Zero to Infinity (AUC∞) [ Time Frame: Day 1 to Day 8 ] 
Measure Type  Secondary 

Measure Title  Area Under the Concentration Time Curve of Brexpiprazole From Time Zero to Infinity (AUC∞) 
Measure Description 
Blood samples were taken at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose/ET. AUC (0  ∞)= AUC from time zero (predose) to extrapolated infinite time (0  ∞). It is obtained from AUC (0  t) plus AUC (t  ∞). The AUC∞ was estimated using the linear trapezoidal rule 
Time Frame  Day 1 to Day 8 
Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. 

PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations. 
Reporting Groups
Description  

Mild Hepatic Impairment  Participants with mild hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function Matched to Mild Hepatic Function. 
Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each participant with normal hepatic function was matched to a participant with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participant with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. 
Moderate Hepatic Impairment  Participants with moderate hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function Matched to Moderate Hepatic Function. 
Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each participant with normal hepatic function was matched to a participant with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. 
Severe Hepatic Impairment  Participants with severe hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function Matched to Severe Hepatic Function. 
Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each participant with normal hepatic function was matched to a participant ith hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. 
Measured Values
Mild Hepatic Impairment  Normal Hepatic Function Matched to Mild Hepatic Function.  Moderate Hepatic Impairment  Normal Hepatic Function Matched to Moderate Hepatic Function.  Severe Hepatic Impairment  Normal Hepatic Function Matched to Severe Hepatic Function.  

Participants Analyzed  7  6  7  7  3  5 
Area Under the Concentration Time Curve of Brexpiprazole From Time Zero to Infinity (AUC∞) [Units: ng*h/mL] Mean (Standard Deviation) 
1827 (1103)  1393 (881)  1960 (579)  1345 (697)  831 (234)  788 (230) 
Statistical Analysis 1 for Area Under the Concentration Time Curve of Brexpiprazole From Time Zero to Infinity (AUC∞)
Groups ^{[1]}  Mild Hepatic Impairment vs. Normal Hepatic Function Matched to Mild Hepatic Function. 

Statistical Test Type ^{[2]}  NonInferiority or Equivalence 
Statistical Method ^{[3]}  Mixed effect analysis of variance 
Geometric Mean Ratio ^{[4]}  1.241 
90% Confidence Interval  0.719 to 2.143 
[1]  Additional details about the analysis, such as null hypothesis and power calculation: 

The secondary comparisons were each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the secondary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the logtransformed data was calculated using a mixed effect analysis of variance.  
[2]  Details of power calculation, definition of noninferiority margin, and other key parameters: 
Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normaltheory CIs, this approach was equivalent to carrying out two 1sided tests of hypothesis at the 5% level of significance.  
[3]  Other relevant method information, such as adjustments or degrees of freedom: 
No text entered.  
[4]  Other relevant estimation information: 
Due to the nature of the normaltheory CIs, this approach is equivalent to carrying out two 1sided tests of hypothesis at the 5% level of significance. 
Statistical Analysis 2 for Area Under the Concentration Time Curve of Brexpiprazole From Time Zero to Infinity (AUC∞)
Groups ^{[1]}  Moderate Hepatic Impairment vs. Normal Hepatic Function Matched to Moderate Hepatic Function. 

Statistical Test Type ^{[2]}  NonInferiority or Equivalence 
Statistical Method ^{[3]}  Mixed effect analysis of variance 
Geometric Mean Ratio ^{[4]}  1.604 
90% Confidence Interval  0.942 to 2.732 
[1]  Additional details about the analysis, such as null hypothesis and power calculation: 

The secondary comparisons were each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the secondary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the logtransformed data was calculated using a mixed effect analysis of variance.  
[2]  Details of power calculation, definition of noninferiority margin, and other key parameters: 
Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normaltheory CIs, this approach was equivalent to carrying out two 1sided tests of hypothesis at the 5% level of significance  
[3]  Other relevant method information, such as adjustments or degrees of freedom: 
No text entered.  
[4]  Other relevant estimation information: 
Due to the nature of the normaltheory CIs, this approach is equivalent to carrying out two 1sided tests of hypothesis at the 5% level of significance. 
Statistical Analysis 3 for Area Under the Concentration Time Curve of Brexpiprazole From Time Zero to Infinity (AUC∞)
Groups ^{[1]}  Severe Hepatic Impairment vs. Normal Hepatic Function Matched to Severe Hepatic Function. 

Statistical Test Type ^{[2]}  NonInferiority or Equivalence 
Statistical Method ^{[3]}  Mixed effect analysis of variance 
Geometric Mean Ratio ^{[4]}  1.077 
90% Confidence Interval  0.540 to 2.146 
[1]  Additional details about the analysis, such as null hypothesis and power calculation: 

The secondary comparisons were each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the secondary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the logtransformed data was calculated using a mixed effect analysis of variance.  
[2]  Details of power calculation, definition of noninferiority margin, and other key parameters: 
Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normaltheory CIs, this approach was equivalent to carrying out two 1sided tests of hypothesis at the 5% level of significance.  
[3]  Other relevant method information, such as adjustments or degrees of freedom: 
No text entered.  
[4]  Other relevant estimation information: 
Due to the nature of the normaltheory CIs, this approach is equivalent to carrying out two 1sided tests of hypothesis at the 5% level of significance. 
6. Secondary:  Maximum Plasma Concentration of Brexpiprazole (Cmax) [ Time Frame: Day 1 to Day 8 ] 
Measure Type  Secondary 

Measure Title  Maximum Plasma Concentration of Brexpiprazole (Cmax) 
Measure Description 
Blood samples were taken at predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose/ET. Cmax is the highest measured concentration of the drug during the dosing interval. Actual blood sample times were used for PK calculations. Values for Cmax and tmax were determined directly from the observed data. 
Time Frame  Day 1 to Day 8 
Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. 

PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations. 
Reporting Groups
Description  

Mild Hepatic Impairment  Participants with mild hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function Matched to Mild Hepatic Function. 
Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each participant with normal hepatic function was matched to a participant with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. 
Moderate Hepatic Impairment  Participants with moderate hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function Matched to Moderate Hepatic Function. 
Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each participant with normal hepatic function was matched to a participant with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. 
Severe Hepatic Impairment  Participants with severe hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function Matched to Severe Hepatic Function. 
Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. 
Measured Values
Mild Hepatic Impairment  Normal Hepatic Function Matched to Mild Hepatic Function.  Moderate Hepatic Impairment  Normal Hepatic Function Matched to Moderate Hepatic Function.  Severe Hepatic Impairment  Normal Hepatic Function Matched to Severe Hepatic Function.  

Participants Analyzed  8  8  8  8  6  6 
Maximum Plasma Concentration of Brexpiprazole (Cmax) [Units: ng/mL] Mean (Standard Deviation) 
22.9 (7.60)  26.7 (9.09)  14.6 (4.63)  19.3 (4.98)  7.65 (2.69)  17.7 (7.38) 
Statistical Analysis 1 for Maximum Plasma Concentration of Brexpiprazole (Cmax)
Groups ^{[1]}  Mild Hepatic Impairment vs. Normal Hepatic Function Matched to Mild Hepatic Function. 

Statistical Test Type ^{[2]}  NonInferiority or Equivalence 
Statistical Method ^{[3]}  Mixed effect analysis of variance 
Geometric mean ratio ^{[4]}  0.856 
90% Confidence Interval  0.691 to 1.059 
[1]  Additional details about the analysis, such as null hypothesis and power calculation: 

The secondary comparisons were each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the secondary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the logtransformed data was calculated using a mixed effect analysis of variance.  
[2]  Details of power calculation, definition of noninferiority margin, and other key parameters: 
Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normaltheory CIs, this approach was equivalent to carrying out two 1sided tests of hypothesis at the 5% level of significance.  
[3]  Other relevant method information, such as adjustments or degrees of freedom: 
No text entered.  
[4]  Other relevant estimation information: 
Due to the nature of the normaltheory CIs, this approach is equivalent to carrying out two 1sided tests of hypothesis at the 5% level of significance. 
Statistical Analysis 2 for Maximum Plasma Concentration of Brexpiprazole (Cmax)
Groups ^{[1]}  Moderate Hepatic Impairment vs. Normal Hepatic Function Matched to Moderate Hepatic Function. 

Statistical Test Type ^{[2]}  NonInferiority or Equivalence 
Statistical Method ^{[3]}  Mixed effect analysis of variance 
Geometric Mean Ratio ^{[4]}  0.742 
90% Confidence Interval  0.599 to 0.918 
[1]  Additional details about the analysis, such as null hypothesis and power calculation: 

The secondary comparisons were each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the secondary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the logtransformed data was calculated using a mixed effect analysis of variance.  
[2]  Details of power calculation, definition of noninferiority margin, and other key parameters: 
Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normaltheory CIs, this approach was equivalent to carrying out two 1sided tests of hypothesis at the 5% level of significance.  
[3]  Other relevant method information, such as adjustments or degrees of freedom: 
No text entered.  
[4]  Other relevant estimation information: 
Due to the nature of the normaltheory CIs, this approach is equivalent to carrying out two 1sided tests of hypothesis at the 5% level of significance. 
Statistical Analysis 3 for Maximum Plasma Concentration of Brexpiprazole (Cmax)
Groups ^{[1]}  Severe Hepatic Impairment vs. Normal Hepatic Function Matched to Severe Hepatic Function. 

Statistical Test Type ^{[2]}  NonInferiority or Equivalence 
Statistical Method ^{[3]}  Mixed effect analysis of variance 
Geometric Mean Ratio ^{[4]}  0.451 
90% Confidence Interval  0.352 to 0.577 
[1]  Additional details about the analysis, such as null hypothesis and power calculation: 

The secondary comparisons were each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the secondary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the logtransformed data was calculated using a mixed effect analysis of variance.  
[2]  Details of power calculation, definition of noninferiority margin, and other key parameters: 
Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normaltheory CIs, this approach was equivalent to carrying out two 1sided tests of hypothesis at the 5% level of significance.  
[3]  Other relevant method information, such as adjustments or degrees of freedom: 
No text entered.  
[4]  Other relevant estimation information: 
Due to the nature of the normaltheory CIs, this approach is equivalent to carrying out two 1sided tests of hypothesis at the 5% level of significance. 
7. Secondary:  Time to Cmax of Brexiprazole (Tmax) [ Time Frame: Day 1 to Day 8 ] 
Measure Type  Secondary 

Measure Title  Time to Cmax of Brexiprazole (Tmax) 
Measure Description 
Blood samples were taken at predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose/ET. Tmax is the time taken to reach highest measured concentration of the drug during the dosing interval. Actual blood sample times were used for PK calculations. Values for Cmax and tmax were determined directly from the observed data. 
Time Frame  Day 1 to Day 8 
Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. 

PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations. 
Reporting Groups
Description  

Mild Hepatic Impairment  Participants with mild hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function Matched to Mild Hepatic Function. 
Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each participant with normal hepatic function was matched to a participant with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. 
Moderate Hepatic Impairment  Participants with moderate hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function Matched to Moderate Hepatic Function. 
Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each participant with normal hepatic function was matched to a participant with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. 
Severe Hepatic Function  Participants with severe hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function Matched to Severe Hepatic Function. 
Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each participant with normal hepatic function was matched to a participant with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. 
Measured Values
Mild Hepatic Impairment  Normal Hepatic Function Matched to Mild Hepatic Function.  Moderate Hepatic Impairment  Normal Hepatic Function Matched to Moderate Hepatic Function.  Severe Hepatic Function  Normal Hepatic Function Matched to Severe Hepatic Function.  

Participants Analyzed  8  8  8  8  6  6 
Time to Cmax of Brexiprazole (Tmax) [Units: h] Median (Full Range) 
3.50 (1.00 to 5.00) 
3.50 (2.00 to 5.00) 
4.50 (3.00 to 24.0) 
4.50 (1.00 to 6.00) 
5.00 (4.00 to 24.0) 
5.00 (2.00 to 6.00) 
No statistical analysis provided for Time to Cmax of Brexiprazole (Tmax)
8. Secondary:  Apparent Clearance of Brexpiprazole From Plasma After Extravascular Administration (CL/F) [ Time Frame: Day 1 to Day 8 ] 
Measure Type  Secondary 

Measure Title  Apparent Clearance of Brexpiprazole From Plasma After Extravascular Administration (CL/F) 
Measure Description 
The value of CL/F (brexpiprazole only) was determined as Dose/AUC∞. Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population PK modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. 
Time Frame  Day 1 to Day 8 
Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. 

PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations. 
Reporting Groups
Description  

Mild Hepatic Impairment  Participants with mild hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function Matched to Mild Hepatic Function. 
Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each participant with normal hepatic function was matched to a participants with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Partipants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. 
Moderate Hepatic Impairment  Participants with moderate hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function Matched to Moderate Hepatic Function. 
Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each participant with normal hepatic function was matched to a participant with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. 
Severe Hepatic Impairment  Participants with severe hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function Matched to Severe Hepatic Function. 
Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each participant with normal hepatic function was matched to a participant with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. 
Measured Values
Mild Hepatic Impairment  Normal Hepatic Function Matched to Mild Hepatic Function.  Moderate Hepatic Impairment  Normal Hepatic Function Matched to Moderate Hepatic Function.  Severe Hepatic Impairment  Normal Hepatic Function Matched to Severe Hepatic Function.  

Participants Analyzed  7  6  7  6  3  5 
Apparent Clearance of Brexpiprazole From Plasma After Extravascular Administration (CL/F) [Units: mL/h/kg] Mean (Standard Deviation) 
24.5 (28.2)  25.4 (12.3)  13.8 (2.72)  26.0 (19.2)  28.2 (6.70)  34.2 (16.3) 
No statistical analysis provided for Apparent Clearance of Brexpiprazole From Plasma After Extravascular Administration (CL/F)
9. Secondary:  Unbound Fraction of Brexpiprazole in Plasma (fu) [ Time Frame: Day 1 to Day 8 ] 
Measure Type  Secondary 

Measure Title  Unbound Fraction of Brexpiprazole in Plasma (fu) 
Measure Description  Blood samples were taken at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose/ET. 
Time Frame  Day 1 to Day 8 
Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. 

PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations. 
Reporting Groups
Description  

Mild Hepatic Function  Participants with mild hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function Matched to Mild Hepatic Function. 
Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each participant with normal hepatic function was matched to a participant with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. 
Moderate Hepatic Function  Participants with moderate hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function Matched to Moderate Hepatic Function. 
Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each participant with normal hepatic function was matched to a participant with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. 
Severe Hepatic Function  Participants with severe hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function Matched to Severe Hepatic Function. 
Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each participant with normal hepatic function was matched to a participant with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. 
Measured Values
Mild Hepatic Function  Normal Hepatic Function Matched to Mild Hepatic Function.  Moderate Hepatic Function  Normal Hepatic Function Matched to Moderate Hepatic Function.  Severe Hepatic Function  Normal Hepatic Function Matched to Severe Hepatic Function.  

Participants Analyzed  8  8  8  8  6  6 
Unbound Fraction of Brexpiprazole in Plasma (fu) [Units: % unbound drug in the urine] Mean (Standard Deviation) 
0.472 (0.0840)  0.451 (0.112)  0.462 (0.0786)  0.400 (0.0442)  0.544 (0.186)  0.450 (0.0795) 
No statistical analysis provided for Unbound Fraction of Brexpiprazole in Plasma (fu)
10. Secondary:  Apparent Unbound Clearance of Brexpiprazole From Plasma After Extravascular Administration (CLu/F) [ Time Frame: Day 1 to Day 8 ] 
Measure Type  Secondary 

Measure Title  Apparent Unbound Clearance of Brexpiprazole From Plasma After Extravascular Administration (CLu/F) 
Measure Description 
Blood samples were taken at predose, 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 concentrationtime curve from time zero to infinity (Dose/AUC∞,u). 
Time Frame  Day 1 to Day 8 
Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. 

PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations. 
Reporting Groups
Description  

Mild Hepatic Impairment  Participants with mild hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function Matched to Mild Hepatic Function. 
Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. 
Moderate Hepatic Function  Participants with moderate hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function Matched to Moderate Hepatic Function. 
Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled 
Severe Hepatic Function  Participants with severe hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function Matched to Severe Hepatic Function. 
Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled 
Measured Values
Mild Hepatic Impairment  Normal Hepatic Function Matched to Mild Hepatic Function.  Moderate Hepatic Function  Normal Hepatic Function Matched to Moderate Hepatic Function.  Severe Hepatic Function  Normal Hepatic Function Matched to Severe Hepatic Function.  

Participants Analyzed  7  6  7  7  3  5 
Apparent Unbound Clearance of Brexpiprazole From Plasma After Extravascular Administration (CLu/F) [Units: mL/h/kg] Mean (Standard Deviation) 
5674 (7165)  5730 (2944)  3115 (494)  6768 (5833)  6598 (1182)  7697 (2653) 
No statistical analysis provided for Apparent Unbound Clearance of Brexpiprazole From Plasma After Extravascular Administration (CLu/F)
11. Secondary:  Terminalphase Elimination Halflife of Brexpiprazole (t1/2,z) [ Time Frame: Day 1 to Day 8 ] 
Measure Type  Secondary 

Measure Title  Terminalphase Elimination Halflife of Brexpiprazole (t1/2,z) 
Measure Description 
Blood samples were taken at predose, 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. Terminalphase elimination halflife is the time measured for the plasma concentration to decrease by one half. 
Time Frame  Day 1 to Day 8 
Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. 

PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations. 
Reporting Groups
Description  

Mild Hepatic Function  Participants with mild hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function Matched to Mild Hepatic Function. 
Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. 
Moderate Hepatic Function  Participants with moderate hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function Matched to Moderate Hepatic Function. 
Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. 
Sever Hepatic Function  Participants with severe hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function Matched to Severe Hepatic Function. 
Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled 
Measured Values
Mild Hepatic Function  Normal Hepatic Function Matched to Mild Hepatic Function.  Moderate Hepatic Function  Normal Hepatic Function Matched to Moderate Hepatic Function.  Sever Hepatic Function  Normal Hepatic Function Matched to Severe Hepatic Function.  

Participants Analyzed  7  6  7  7  3  5 
Terminalphase Elimination Halflife of Brexpiprazole (t1/2,z) [Units: h] Mean (Standard Deviation) 
103 (51.1)  64.7 (24.6)  116 (25.8)  64.2 (26.2)  81.1 (17.1)  51.4 (8.21) 
No statistical analysis provided for Terminalphase Elimination Halflife of Brexpiprazole (t1/2,z)
12. Secondary:  Renal Clearance (CLr) of Brexipiprazole [ Time Frame: Day 1 to Day 8 ] 
Measure Type  Secondary 

Measure Title  Renal Clearance (CLr) of Brexipiprazole 
Measure Description 
Urine samples were taken at predose and during the following increments: 0 to 24, 24 to 48, 48 to 72, 72 to 96, 96 to 120, 120 to 144, and 144 to 168 hours postdose. The value of CLr was calculated as Ae,u/AUCt. 
Time Frame  Day 1 to Day 8 
Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. 

PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations. 
Reporting Groups
Description  

Mild Hepatic Impairment  Participants with mild hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function Matched to Mild Hepatic Function. 
Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. 
Moderate Hepatic Impairment  Participants with moderate hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function Matched to Moderate Hepatic Function. 
Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. 
Severe Hepatic Impairment  Participants with severe hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function Matched to Severe Hepatic Function. 
Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. 
Measured Values
Mild Hepatic Impairment  Normal Hepatic Function Matched to Mild Hepatic Function.  Moderate Hepatic Impairment  Normal Hepatic Function Matched to Moderate Hepatic Function.  Severe Hepatic Impairment  Normal Hepatic Function Matched to Severe Hepatic Function.  

Participants Analyzed  8  8  8  8  6  6 
Renal Clearance (CLr) of Brexipiprazole [Units: mL/h/kg] Mean (Standard Deviation) 
0.0468 (0.0353)  0.0263 (0.0244)  0.0360 (0.0286)  0.0422 (0.0383)  0.0402 (0.0872)  0.0193 (0.0203) 
No statistical analysis provided for Renal Clearance (CLr) of Brexipiprazole
13. Secondary:  Cumulative Amount of Brexpiprazole Excreted Into the Urine (Ae,u) [ Time Frame: Day 1 to Day 8 ] 
Measure Type  Secondary 

Measure Title  Cumulative Amount of Brexpiprazole Excreted Into the Urine (Ae,u) 
Measure Description 
Urine samples were taken at predose and during the following increments: 0 to 24, 24 to 48, 48 to 72, 72 to 96, 96 to 120, 120 to 144, and 144 to 168 hours postdose. The value of Ae,u was calculated as the summation of urine concentration × urine volume from each collection interval 
Time Frame  Day 1 to Day 8 
Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. 

PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations. 
Reporting Groups
Description  

Mild Hepatic Function  Participants with mild hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function Matched to Mild Hepatic Function. 
Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. 
Moderate Hepatic Function  Participants with moderate hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function Matched to Moderate Hepatic Function. 
Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. 
Severe Hepatic Function  Participants with severe hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function Matched to Severe Hepatic Function. 
Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. 
Measured Values
Mild Hepatic Function  Normal Hepatic Function Matched to Mild Hepatic Function.  Moderate Hepatic Function  Normal Hepatic Function Matched to Moderate Hepatic Function.  Severe Hepatic Function  Normal Hepatic Function Matched to Severe Hepatic Function.  

Participants Analyzed  8  8  8  8  6  6 
Cumulative Amount of Brexpiprazole Excreted Into the Urine (Ae,u) [Units: Ng] Mean (Standard Deviation) 
4511 (3808)  1854 (1500)  3522 (2740)  3837 (3358)  2090 (4699)  1326 (1427) 
No statistical analysis provided for Cumulative Amount of Brexpiprazole Excreted Into the Urine (Ae,u)
14. Secondary:  Fraction of Systemically Available Brexpiprazole Excreted Into the Urine (fe,u) [ Time Frame: Day 1 to Day 8 ] 
Measure Type  Secondary 

Measure Title  Fraction of Systemically Available Brexpiprazole Excreted Into the Urine (fe,u) 
Measure Description 
Urine samples were taken at predose and during the following increments: 0 to 24, 24 to 48, 48 to 72, 72 to 96, 96 to 120, 120 to 144, and 144 to 168 hours postdose.. The value of fe,u was calculated as 100 × Ae,u/Dose. 
Time Frame  Day 1 to Day 8 
Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. 

PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations. 
Reporting Groups
Description  

Mild Hepatic Impairment  Participants with mild hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function Matched to Mild Hepatic Function. 
Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. 
Moderate Hepatic Impairment  Participants with moderate hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function Matched to Moderate Hepatic Function 
Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. 
Severe Hepatic Impairment  Participants with severe hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function Matched to Severe Hepatic Function. 
Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. 
Measured Values
Mild Hepatic Impairment  Normal Hepatic Function Matched to Mild Hepatic Function.  Moderate Hepatic Impairment  Normal Hepatic Function Matched to Moderate Hepatic Function  Severe Hepatic Impairment  Normal Hepatic Function Matched to Severe Hepatic Function.  

Participants Analyzed  8  8  8  8  6  6 
Fraction of Systemically Available Brexpiprazole Excreted Into the Urine (fe,u) [Units: % of drug in urine] Mean (Standard Deviation) 
0.226 (0.190)  0.0927 (0.0750)  0.176 (0.137)  0.192 (0.168)  0.104 (0.235)  0.0663 (0.0713) 
No statistical analysis provided for Fraction of Systemically Available Brexpiprazole Excreted Into the Urine (fe,u)
15. Secondary:  AUCt for DM3411 Metabolite [ Time Frame: Day 1 to Day 8 ] 
Measure Type  Secondary 

Measure Title  AUCt for DM3411 Metabolite 
Measure Description 
Blood samples were taken at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose/ET. AUCt= Area under the plasma concentration versus time curve from time zero (predose) to time of last quantifiable concentration (0t) The AUCt was estimated using the linear trapezoidal rule. 
Time Frame  Day 1 to Day 8 
Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. 

PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations. 
Reporting Groups
Description  

Mild Hepatic Impairment  Participants with mild hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function Matched to Mild Hepatic Function. 
Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. 
Moderate Hepatic Impairment  Participants with moderate hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function Matched to Moderate Hepatic Function. 
Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. 
Severe Hepatic Impairment  Participants with severe hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function Matched to Severe Hepatic Function. 
Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. 
Measured Values
Mild Hepatic Impairment  Normal Hepatic Function Matched to Mild Hepatic Function.  Moderate Hepatic Impairment  Normal Hepatic Function Matched to Moderate Hepatic Function.  Severe Hepatic Impairment  Normal Hepatic Function Matched to Severe Hepatic Function.  

Participants Analyzed  8  8  8  8  6  6 
AUCt for DM3411 Metabolite [Units: ng*h/mL] Mean (Standard Deviation) 
380 (195)  683 (246)  284 (164)  486 (263)  151 (51.4)  479 (226) 
Statistical Analysis 1 for AUCt for DM3411 Metabolite
Groups ^{[1]}  Mild Hepatic Impairment vs. Normal Hepatic Function Matched to Mild Hepatic Function. 

Statistical Test Type ^{[2]}  NonInferiority or Equivalence 
Statistical Method ^{[3]}  Mixed effect analysis of variance 
Geometric Mean Ratio ^{[4]}  0.509 
90% Confidence Interval  0.346 to 0.748 
[1]  Additional details about the analysis, such as null hypothesis and power calculation: 

The secondary comparisons were each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the secondary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the logtransformed data was calculated using a mixed effect analysis of variance.  
[2]  Details of power calculation, definition of noninferiority margin, and other key parameters: 
Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normaltheory CIs, this approach was equivalent to carrying out two 1sided tests of hypothesis at the 5% level of significance.  
[3]  Other relevant method information, such as adjustments or degrees of freedom: 
No text entered.  
[4]  Other relevant estimation information: 
No text entered. 
Statistical Analysis 2 for AUCt for DM3411 Metabolite
Groups ^{[1]}  Moderate Hepatic Impairment vs. Normal Hepatic Function Matched to Moderate Hepatic Function. 

Statistical Test Type ^{[2]}  NonInferiority or Equivalence 
Statistical Method ^{[3]}  Mixed effect analysis of variance 
Geometric Mean Ratio ^{[4]}  0.586 
90% Confidence Interval  0.399 to 0.861 
[1]  Additional details about the analysis, such as null hypothesis and power calculation: 

The secondary comparisons were each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the secondary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the logtransformed data was calculated using a mixed effect analysis of variance.  
[2]  Details of power calculation, definition of noninferiority margin, and other key parameters: 
Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normaltheory CIs, this approach was equivalent to carrying out two 1sided tests of hypothesis at the 5% level of significance.  
[3]  Other relevant method information, such as adjustments or degrees of freedom: 
No text entered.  
[4]  Other relevant estimation information: 
Due to the nature of the normaltheory CIs, this approach is equivalent to carrying out two 1sided tests of hypothesis at the 5% level of significance. 
Statistical Analysis 3 for AUCt for DM3411 Metabolite
Groups ^{[1]}  Severe Hepatic Impairment vs. Normal Hepatic Function Matched to Severe Hepatic Function. 

Statistical Test Type ^{[2]}  NonInferiority or Equivalence 
Statistical Method ^{[3]}  Mixed effect analysis of variance 
Geometric Mean Ratio ^{[4]}  0.334 
90% Confidence Interval  0.214 to 0.521 
[1]  Additional details about the analysis, such as null hypothesis and power calculation: 

The secondary comparisons were each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the secondary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the logtransformed data was calculated using a mixed effect analysis of variance.  
[2]  Details of power calculation, definition of noninferiority margin, and other key parameters: 
Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normaltheory CIs, this approach was equivalent to carrying out two 1sided tests of hypothesis at the 5% level of significance.  
[3]  Other relevant method information, such as adjustments or degrees of freedom: 
No text entered.  
[4]  Other relevant estimation information: 
Due to the nature of the normaltheory CIs, this approach is equivalent to carrying out two 1sided tests of hypothesis at the 5% level of significance. 
16. Secondary:  AUC∞ for DM3411 Metabolite [ Time Frame: Day 1 to Day 8 ] 
Measure Type  Secondary 

Measure Title  AUC∞ for DM3411 Metabolite 
Measure Description 
Blood samples were taken at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose/ET. The AUC∞ were estimated using the linear trapezoidal rule. 
Time Frame  Day 1 to Day 8 
Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. 

PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations. 
Reporting Groups
Description  

Mild Hepatic Impairment  Participants with mild hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function Matched to Mild Hepatic Function. 
Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. 
Moderate Hepatic Impairment  Participants with moderate hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function Matched to Moderate Hepatic Function. 
Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. 
Severe Hepatic Impairment  Participants with severe hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function Matched to Severe Hepatic Function. 
Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. 
Measured Values
Mild Hepatic Impairment  Normal Hepatic Function Matched to Mild Hepatic Function.  Moderate Hepatic Impairment  Normal Hepatic Function Matched to Moderate Hepatic Function.  Severe Hepatic Impairment  Normal Hepatic Function Matched to Severe Hepatic Function.  

Participants Analyzed  5  6  6  6  4  3 
AUC∞ for DM3411 Metabolite [Units: ng*h/mL] Mean (Standard Deviation) 
489 (210)  692 (259)  382 (262)  530 (211)  187 (67.2)  329 (167) 
Statistical Analysis 1 for AUC∞ for DM3411 Metabolite
Groups ^{[1]}  Mild Hepatic Impairment vs. Normal Hepatic Function Matched to Mild Hepatic Function. 

Statistical Test Type ^{[2]}  NonInferiority or Equivalence 
Statistical Method ^{[3]}  Mixed effect analysis of variance 
Geometric Mean Ratio ^{[4]}  0.716 
90% Confidence Interval  0.445 to 1.153 
[1]  Additional details about the analysis, such as null hypothesis and power calculation: 

The secondary comparisons were each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the secondary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the logtransformed data was calculated using a mixed effect analysis of variance.  
[2]  Details of power calculation, definition of noninferiority margin, and other key parameters: 
Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normaltheory CIs, this approach was equivalent to carrying out two 1sided tests of hypothesis at the 5% level of significance.  
[3]  Other relevant method information, such as adjustments or degrees of freedom: 
No text entered.  
[4]  Other relevant estimation information: 
No text entered. 
Statistical Analysis 2 for AUC∞ for DM3411 Metabolite
Groups ^{[1]}  Moderate Hepatic Impairment vs. Normal Hepatic Function Matched to Moderate Hepatic Function. 

Statistical Test Type ^{[2]}  NonInferiority or Equivalence 
Statistical Method ^{[3]}  Mixed effect analysis of variance 
Geometric Mean Ratio ^{[4]}  0.594 
90% Confidence Interval  0.378 to 0.934 
[1]  Additional details about the analysis, such as null hypothesis and power calculation: 

The secondary comparisons were each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the secondary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the logtransformed data was calculated using a mixed effect analysis of variance.  
[2]  Details of power calculation, definition of noninferiority margin, and other key parameters: 
Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normaltheory CIs, this approach was equivalent to carrying out two 1sided tests of hypothesis at the 5% level of significance.  
[3]  Other relevant method information, such as adjustments or degrees of freedom: 
No text entered.  
[4]  Other relevant estimation information: 
No text entered. 
Statistical Analysis 3 for AUC∞ for DM3411 Metabolite
Groups ^{[1]}  Severe Hepatic Impairment vs. Normal Hepatic Function Matched to Severe Hepatic Function. 

Statistical Test Type ^{[2]}  NonInferiority or Equivalence 
Statistical Method ^{[3]}  Mixed effect analysis of variance 
Geometric Mean Ratio ^{[4]}  0.561 
90% Confidence Interval  0.308 to 1.022 
[1]  Additional details about the analysis, such as null hypothesis and power calculation: 

The secondary comparisons were each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the secondary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the logtransformed data was calculated using a mixed effect analysis of variance.  
[2]  Details of power calculation, definition of noninferiority margin, and other key parameters: 
Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normaltheory CIs, this approach was equivalent to carrying out two 1sided tests of hypothesis at the 5% level of significance.  
[3]  Other relevant method information, such as adjustments or degrees of freedom: 
No text entered.  
[4]  Other relevant estimation information: 
No text entered. 
17. Secondary:  Cmax for DM3411 Metabolite [ Time Frame: Day 1 to Day 8 ] 
Measure Type  Secondary 

Measure Title  Cmax for DM3411 Metabolite 
Measure Description  Blood samples were taken at predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose/ET. Cmax is the highest measured concentration of the metabolite during the dosing interval. 
Time Frame  Day 1 to Day 8 
Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. 

PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations. 
Reporting Groups
Description  

Mild Hepatic Impairment  Participants with mild hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function Matched to Mild Hepatic Function. 
Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. 
Moderate Hepatic Impairment  Participants with moderate hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function Matched to Moderate Hepatic Function. 
Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled 
Severe Hepatic Impairment  Participants with severe hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function Matched to Severe Hepatic Function. 
Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. 
Measured Values
Mild Hepatic Impairment  Normal Hepatic Function Matched to Mild Hepatic Function.  Moderate Hepatic Impairment  Normal Hepatic Function Matched to Moderate Hepatic Function.  Severe Hepatic Impairment  Normal Hepatic Function Matched to Severe Hepatic Function.  

Participants Analyzed  8  8  8  8  6  6 
Cmax for DM3411 Metabolite [Units: ng/mL] Mean (Standard Deviation) 
6.49 (5.13)  10.5 (4.26)  3.19 (1.56)  7.25 (4.83)  2.15 (0.880)  7.13 (3.73) 
Statistical Analysis 1 for Cmax for DM3411 Metabolite
Groups ^{[1]}  Mild Hepatic Impairment vs. Normal Hepatic Function Matched to Mild Hepatic Function. 

Statistical Test Type ^{[2]}  NonInferiority or Equivalence 
Statistical Method ^{[3]}  Mixed effect analysis of variance 
Geometric Mean Ratio ^{[4]}  0.558 
90% Confidence Interval  0.368 to 0.845 
[1]  Additional details about the analysis, such as null hypothesis and power calculation: 

The secondary comparisons were each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the secondary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the logtransformed data was calculated using a mixed effect analysis of variance.  
[2]  Details of power calculation, definition of noninferiority margin, and other key parameters: 
Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normaltheory CIs, this approach was equivalent to carrying out two 1sided tests of hypothesis at the 5% level of significance.  
[3]  Other relevant method information, such as adjustments or degrees of freedom: 
No text entered.  
[4]  Other relevant estimation information: 
No text entered. 
Statistical Analysis 2 for Cmax for DM3411 Metabolite
Groups ^{[1]}  Moderate Hepatic Impairment vs. Normal Hepatic Function Matched to Moderate Hepatic Function. 

Statistical Test Type ^{[2]}  NonInferiority or Equivalence 
Statistical Method ^{[3]}  Mixed effect analysis of variance 
Geometric Mean Ratio ^{[4]}  0.516 
90% Confidence Interval  0.341 to 0.781 
[1]  Additional details about the analysis, such as null hypothesis and power calculation: 

The secondary comparisons were each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the secondary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the logtransformed data was calculated using a mixed effect analysis of variance.  
[2]  Details of power calculation, definition of noninferiority margin, and other key parameters: 
Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normaltheory CIs, this approach was equivalent to carrying out two 1sided tests of hypothesis at the 5% level of significance.  
[3]  Other relevant method information, such as adjustments or degrees of freedom: 
No text entered.  
[4]  Other relevant estimation information: 
No text entered. 
Statistical Analysis 3 for Cmax for DM3411 Metabolite
Groups ^{[1]}  Severe Hepatic Impairment vs. Normal Hepatic Function Matched to Severe Hepatic Function. 

Statistical Test Type ^{[2]}  NonInferiority or Equivalence 
Statistical Method ^{[3]}  Mixed effect analysis of variance 
Geometric Mean Ratio ^{[4]}  0.314 
90% Confidence Interval  0.195 to 0.507 
[1]  Additional details about the analysis, such as null hypothesis and power calculation: 

The secondary comparisons were each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the secondary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the logtransformed data was calculated using a mixed effect analysis of variance.  
[2]  Details of power calculation, definition of noninferiority margin, and other key parameters: 
Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normaltheory CIs, this approach was equivalent to carrying out two 1sided tests of hypothesis at the 5% level of significance.  
[3]  Other relevant method information, such as adjustments or degrees of freedom: 
No text entered.  
[4]  Other relevant estimation information: 
No text entered. 
18. Secondary:  Tmax for DM3411 Metabolite [ Time Frame: Day 1 to Day 8 ] 
Measure Type  Secondary 

Measure Title  Tmax for DM3411 Metabolite 
Measure Description  Blood samples were taken at predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose/ET. Tmax is the time taken to reach highest measured concentration of the metabolite during the dosing interval. 
Time Frame  Day 1 to Day 8 
Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. 

PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations. 
Reporting Groups
Description  

Mild Hepatic Function  Participants with mild hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function Matched to Mild Hepatic Function. 
Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. 
Moderate Hepatic Function  Participants with moderate hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function Matched to Moderate Hepatic Function. 
Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. 
Severe Hepatic Function  Participants with severe hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function Matched to Severe Hepatic Function. 
Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. 
Measured Values
Mild Hepatic Function  Normal Hepatic Function Matched to Mild Hepatic Function.  Moderate Hepatic Function  Normal Hepatic Function Matched to Moderate Hepatic Function.  Severe Hepatic Function  Normal Hepatic Function Matched to Severe Hepatic Function.  

Participants Analyzed  8  8  8  8  6  6 
Tmax for DM3411 Metabolite [Units: h] Median (Full Range) 
5.00 (2.00 to 24.0) 
6.00 (5.00 to 24.0) 
5.00 (2.00 to 24.0) 
7.00 (2.00 to 24.0) 
4.5 (3.00 to 24.0) 
6.00 (5.00 to 16.0) 
No statistical analysis provided for Tmax for DM3411 Metabolite
19. Secondary:  t1/2,z for DM3411 Metabolite [ Time Frame: Day 1 to Day 8 ] 
Measure Type  Secondary 

Measure Title  t1/2,z for DM3411 Metabolite 
Measure Description 
Blood samples were taken at predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose/ET. The t1/2,z was determined as (ln2)/λz. 
Time Frame  Day 1 to Day 8 
Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. 

PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations. 
Reporting Groups
Description  

Mild Hepatic Impairment  Participants with mild hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function Matched to Mild Hepatic Function. 
Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. 
Moderate Hepatic Impairment  Participants with moderate hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function Matched to Moderate Hepatic Function. 
Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. 
Severe Hepatic Impairment  Participants with severe hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function Matched to Severe Hepatic Function. 
Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. 
Measured Values
Mild Hepatic Impairment  Normal Hepatic Function Matched to Mild Hepatic Function.  Moderate Hepatic Impairment  Normal Hepatic Function Matched to Moderate Hepatic Function.  Severe Hepatic Impairment  Normal Hepatic Function Matched to Severe Hepatic Function.  

Participants Analyzed  5  6  6  6  4  3 
t1/2,z for DM3411 Metabolite [Units: h] Mean (Standard Deviation) 
78.8 (37.6)  59.7 (15.7)  87.2 (45.7)  62.0 (26.4)  84.6 (12.0)  56.1 (8.25) 
No statistical analysis provided for t1/2,z for DM3411 Metabolite
20. Secondary:  Ae,u for DM3411 Metabolite [ Time Frame: Day 1 to Day 8 ] 
Measure Type  Secondary 

Measure Title  Ae,u for DM3411 Metabolite 
Measure Description 
Urine samples were taken at predose and during the following increments: 0 to 24, 24 to 48, 48 to 72, 72 to 96, 96 to 120, 120 to 144, and 144 to 168 hours postdose. The value of Ae,u was calculated as the summation of urine concentration × urine volume from each collection interval. 
Time Frame  Day 1 to Day 8 
Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. 

PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations. 
Reporting Groups
Description  

Mild Hepatic Function  Participants with mild hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function Matched to Mild Hepatic Function. 
Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. 
Moderate Hepatic Function  Participants with moderate hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function Matched to Moderate Hepatic Function. 
Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled 
Severe Hepatic Function  Participants with severe hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function Matched to Severe Hepatic Function. 
Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. 
Measured Values
Mild Hepatic Function  Normal Hepatic Function Matched to Mild Hepatic Function.  Moderate Hepatic Function  Normal Hepatic Function Matched to Moderate Hepatic Function.  Severe Hepatic Function  Normal Hepatic Function Matched to Severe Hepatic Function.  

Participants Analyzed  8  8  8  8  6  6 
Ae,u for DM3411 Metabolite [Units: Ng] Mean (Standard Deviation) 
67086 (25276)  81148 (23188)  68413 (16993)  71353 (41630)  48190 (14756)  83604 (34907) 
No statistical analysis provided for Ae,u for DM3411 Metabolite
21. Secondary:  fe,u for DM3411 Metabolite [ Time Frame: Day 1 to Day 8 ] 
Measure Type  Secondary 

Measure Title  fe,u for DM3411 Metabolite 
Measure Description 
Urine samples were taken at predose and during the following increments: 0 to 24, 24 to 48, 48 to 72, 72 to 96, 96 to 120, 120 to 144, and 144 to 168 hours postdose. The value of fe,u was calculated as 100 × Ae,u/Dose. 
Time Frame  Day 1 to Day 8 
Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. 

PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations. 
Reporting Groups
Description  

Mild Hepatic Function  Participants with mild hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function Matched to Mild Hepatic Function. 
Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. 
Moderate Hepatic Function  Participants with moderate hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg 
Normal Hepatic Function Matched to Moderate Hepatic Function. 
Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. 
Severe Hepatic Function  Participants with severe hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function Matched to Severe Hepatic Function. 
Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. 
Measured Values
Mild Hepatic Function  Normal Hepatic Function Matched to Mild Hepatic Function.  Moderate Hepatic Function  Normal Hepatic Function Matched to Moderate Hepatic Function.  Severe Hepatic Function  Normal Hepatic Function Matched to Severe Hepatic Function.  

Participants Analyzed  8  8  8  8  6  6 
fe,u for DM3411 Metabolite [Units: % metabolite excreted in urine] Mean (Standard Deviation) 
3.23 (1.22)  3.91 (1.12)  3.30 (0.819)  3.44 (2.01)  2.32 (0.712)  4.03 (1.68) 
No statistical analysis provided for fe,u for DM3411 Metabolite
22. Secondary:  CLr for DM3411 Metabolite [ Time Frame: Day 1 to Day 8 ] 
Measure Type  Secondary 

Measure Title  CLr for DM3411 Metabolite 
Measure Description 
Urine samples were taken at predose and during the following increments: 0 to 24, 24 to 48, 48 to 72, 72 to 96, 96 to 120, 120 to 144, and 144 to 168 hours postdose. The value of CLr was calculated as Ae,u/AUCt. 
Time Frame  Day 1 to Day 8 
Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. 

PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations. 
Reporting Groups
Description  

Mild Hepatic Impairment  Participants with mild hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function Matched to Mild Hepatic Function. 
Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. 
Moderate Hepatic Impairment  Participants with moderate hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function Matched to Moderate Hepatic Function. 
Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. 
Severe Hepatic Impairment  Participants with severe hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function Matched to Severe Hepatic Function. 
Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. 
Measured Values
Mild Hepatic Impairment  Normal Hepatic Function Matched to Mild Hepatic Function.  Moderate Hepatic Impairment  Normal Hepatic Function Matched to Moderate Hepatic Function.  Severe Hepatic Impairment  Normal Hepatic Function Matched to Severe Hepatic Function.  

Participants Analyzed  8  8  8  8  6  6 
CLr for DM3411 Metabolite [Units: mL/h/kg] Mean (Standard Deviation) 
2.67 (1.31)  1.83 (0.828)  3.96 (2.32)  1.90 (0.568)  4.08 (1.68)  2.33 (1.01) 
No statistical analysis provided for CLr for DM3411 Metabolite
23. Secondary:  Number of Adverse Events (AEs) Reported [ Time Frame: From the time the Informed Consent Form was signed, throughout the 8 day study up to 30 days after study drug administration. ] 
Measure Type  Secondary 

Measure Title  Number of Adverse Events (AEs) Reported 
Measure Description  AEs were captured for all participants from the time the ICF was signed until the end of the study 
Time Frame  From the time the Informed Consent Form was signed, throughout the 8 day study up to 30 days after study drug administration. 
Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. 

Participants who received at least one dose of study drug were included in the safety analysis. 
Reporting Groups
Description  

Mild Hepatic Impairment  Participants with mild hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Moderate Hepatic Impairment  Participants with moderate hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Severe Hepatic Impairment  Participants with severe hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function  Participants with normal hepatic function (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Measured Values
Mild Hepatic Impairment  Moderate Hepatic Impairment  Severe Hepatic Impairment  Normal Hepatic Function  

Participants Analyzed  8  8  6  23 
Number of Adverse Events (AEs) Reported [Units: Events] 

Adverse events  3  5  1  8 
Treatment emergent adverse events  3  5  1  6 
Serious adverse events  0  0  0  0 
No statistical analysis provided for Number of Adverse Events (AEs) Reported
24. Secondary:  Number of Participants With Changes From Baseline in Vital Signs Parameters. [ Time Frame: Day 1 to Day 8 ] 
Measure Type  Secondary 

Measure Title  Number of Participants With Changes From Baseline in Vital Signs Parameters. 
Measure Description  Vital signs (including blood pressure, heart rate, temperature, and respiratory rate) were assessed at Screening, Day 1, Day 1 at predose (within 45 minutes prior to dosing), and 2, 4, 6, 8, 12, 24, 72, 120, and 168/ET hours postdose. Blood pressure and heart rate were taken with the subject in the supine (performed first), sitting, and standing 
Time Frame  Day 1 to Day 8 
Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. 

The abnormal values of vital signs values in participants are captured as serious AEs/AEs and are reported in the SAE or other AE section of this results report. 
Reporting Groups
Description  

Mild Hepatic Impairment  Participants with mild hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Moderate Hepatic Impairment  Participants with moderate hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Severe Hepatic Impairment  Participants with severe hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function  Participants with normal hepatic function (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Measured Values
Mild Hepatic Impairment  Moderate Hepatic Impairment  Severe Hepatic Impairment  Normal Hepatic Function  

Participants Analyzed  8  8  6  23 
Number of Participants With Changes From Baseline in Vital Signs Parameters. [Units: Participants] 
0  0  0  0 
No statistical analysis provided for Number of Participants With Changes From Baseline in Vital Signs Parameters.
25. Secondary:  Number of Participants With Changes From Baseline in Electrocardiogram (ECG) Parameters. [ Time Frame: Day1 to Day 8 ] 
Measure Type  Secondary 

Measure Title  Number of Participants With Changes From Baseline in Electrocardiogram (ECG) Parameters. 
Measure Description  Electrocardiograms were performed at Screening, Day 1, and Day 1 at predose (in triplicate; within 45 minutes prior to dosing), and 2, 4, 6, 8, 12, 24, 72, 120, and 168/ET hours postdose. Standard 12lead ECGs were performed after the subject was supine and at rest for ≥ 10 minutes prior to the ECG. 
Time Frame  Day1 to Day 8 
Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. 

The abnormal values of ECG values in participants are captured as serious AEs/AEs and are reported in the SAE or other AE section of this results report. 
Reporting Groups
Description  

Mild Hepatic Impairment  Participants with mild hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Moderate Hepatic Impairment  Participants with moderate hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Severe Hepatic Impairment  Participants with severe hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function  Participants with normal hepatic function (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Measured Values
Mild Hepatic Impairment  Moderate Hepatic Impairment  Severe Hepatic Impairment  Normal Hepatic Function  

Participants Analyzed  8  8  6  23 
Number of Participants With Changes From Baseline in Electrocardiogram (ECG) Parameters. [Units: Participants] 
0  0  0  0 
No statistical analysis provided for Number of Participants With Changes From Baseline in Electrocardiogram (ECG) Parameters.
26. Secondary:  Number of Participants With Changes From Baseline in Serum Chemistry, Hematology and Urinalysis Parameters. [ Time Frame: Day 1 to Day 8 ] 
Measure Type  Secondary 

Measure Title  Number of Participants With Changes From Baseline in Serum Chemistry, Hematology and Urinalysis Parameters. 
Measure Description  Hematology, serum chemistry, and urinalysis, including prothrombin time, international normalized ratio, partial thromboplastin time, and activated partial thromboplastin time, were completed at Screening, Day 1, Day 3 (48 hours postdose), and Day 8 (168 hours postdose)/ET. 
Time Frame  Day 1 to Day 8 
Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. 

The abnormal values of laboratory values in participants are captured as serious AEs/AEs and are reported in the SAE or other AE section of this results report. 
Reporting Groups
Description  

Mild Hepatic Impairment  Participants with mild hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Moderate Hepatic Impairment  Participants with moderate hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Severe Hepatic Impairment  Participants with severe hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function  Participants with normal hepatic function (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Measured Values
Mild Hepatic Impairment  Moderate Hepatic Impairment  Severe Hepatic Impairment  Normal Hepatic Function  

Participants Analyzed  8  8  6  23 
Number of Participants With Changes From Baseline in Serum Chemistry, Hematology and Urinalysis Parameters. [Units: Participant] 
0  0  0  0 
No statistical analysis provided for Number of Participants With Changes From Baseline in Serum Chemistry, Hematology and Urinalysis Parameters.
27. Secondary:  Incidence of Suicidality, Suicidal Behaviour or Suicidal Ideation as Measured by the ColumbiaSuicide Severity Rating Scale (CSSRS) [ Time Frame: Day 1, Day 4, Day 7 ] 
Measure Type  Secondary 

Measure Title  Incidence of Suicidality, Suicidal Behaviour or Suicidal Ideation as Measured by the ColumbiaSuicide Severity Rating Scale (CSSRS) 
Measure Description  The Baseline version of the CSSRS was administered at Screening. The Since Last Visit version of the CSSRS was administered on Day 1 at predose and on Days 4 and 7. 
Time Frame  Day 1, Day 4, Day 7 
Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. 

Suicidality, suicidal behaviour or suicidal ideation are captured as serious AEs/AEs and are reported in the SAE or other AE section of this results report. 
Reporting Groups
Description  

Mild Hepatic Impairment  Participants with mild hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Moderate Hepatic Impairment  Participants with moderate hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Severe Hepatic Impairment  Participants with severe hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function  Participants with normal hepatic function (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Measured Values
Mild Hepatic Impairment  Moderate Hepatic Impairment  Severe Hepatic Impairment  Normal Hepatic Function  

Participants Analyzed  8  8  6  23 
Incidence of Suicidality, Suicidal Behaviour or Suicidal Ideation as Measured by the ColumbiaSuicide Severity Rating Scale (CSSRS) [Units: Participants] 
0  0  0  0 
No statistical analysis provided for Incidence of Suicidality, Suicidal Behaviour or Suicidal Ideation as Measured by the ColumbiaSuicide Severity Rating Scale (CSSRS)
Serious Adverse Events
Other Adverse Events
Time Frame  Adverse events were recorded from the time the Informed Consent Form was signed, throughout the 8 day study up to 30 days after study drug administration. 

Additional Description  The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. 
Frequency Threshold
Threshold above which other adverse events are reported  0% 

Reporting Groups
Description  

Mild Hepatic Impairment  Participants with mild hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Moderate Hepatic Impairment  Participants with moderate hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Severe Hepatic Impairment  Participants with severe hepatic impairment (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Normal Hepatic Function  Participants with normal hepatic function (ChildPugh classification scheme) received a single oral dose of brexpiprazole 2 mg. 
Other Adverse Events
Mild Hepatic Impairment  Moderate Hepatic Impairment  Severe Hepatic Impairment  Normal Hepatic Function  

Total, Other (not including serious) Adverse Events  
# participants affected / at risk  3/8 (37.50%)  3/8 (37.50%)  1/6 (16.67%)  6/23 (26.09%) 
Gastrointestinal disorders  
Diarrhoea ^{* 1 }  
# participants affected / at risk  0/8 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/23 (0.00%) 
General disorders  
Fatigue ^{* 1 }  
# participants affected / at risk  1/8 (12.50%)  1/8 (12.50%)  0/6 (0.00%)  0/23 (0.00%) 
Musculoskeletal and connective tissue disorders  
Musculoskeletal pain ^{* 1 }  
# participants affected / at risk  0/8 (0.00%)  0/8 (0.00%)  0/6 (0.00%)  1/23 (4.35%) 
Nervous system disorders  
Dizziness ^{* 1 }  
# participants affected / at risk  1/8 (12.50%)  0/8 (0.00%)  0/6 (0.00%)  0/23 (0.00%) 
Headache ^{* 1 }  
# participants affected / at risk  1/8 (12.50%)  1/8 (12.50%)  1/6 (16.67%)  4/23 (17.39%) 
Somnolence ^{* 1 }  
# participants affected / at risk  0/8 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  1/23 (4.35%) 
Respiratory, thoracic and mediastinal disorders  
Cough ^{* 1 }  
# participants affected / at risk  0/8 (0.00%)  1/8 (12.50%)  0/6 (0.00%)  0/23 (0.00%) 
*  Events were collected by nonsystematic assessment 

1  Term from vocabulary, MedDRA 
Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data 

No text entered. 
More Information
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:
Organization: Otsuka Pharmaceutical Development and Commercialization, Inc.
phone: 8005623974
Responsible Party:  Otsuka Pharmaceutical Development & Commercialization, Inc. 
ClinicalTrials.gov Identifier:  NCT01299454 History of Changes 
Other Study ID Numbers: 
33109225 
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 