Trial Outcomes & Findings for A Study Evaluating the of OPC-34712 in Subjects With Normal Hepatic Function and Hepatically Impaired Subjects (NCT NCT01299454)

NCT ID: NCT01299454

Last Updated: 2015-10-20

Results Overview

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

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 45 participants
• Primary outcome timeframe: Day 1 to Day 8
• Results posted on: 2015-10-20

Participant Flow

81 participants were screened; of these 45 participants were enrolled recruited at 3 study sites in the United States (US).

Participant milestones

Measure	Mild Hepatic Impairment Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 milligrams (mg).	Moderate Hepatic Impairment Participants with moderate hepatic impairment (Child-Pugh classification scheme)received a single dose of oral brexpiprazole 2 mg.	Severe Hepatic Impairment Participants with severe hepatic impairment (based on Child-Pugh classification scheme) received a single dose of oral brexpiprazole 2 mg.	Normal Hepatic Function Participants with normal hepatic function (based on Child-Pugh classification scheme) received a single dose of oral brexpiprazole 2 mg.
Overall Study STARTED	8	8	6	23
Overall Study COMPLETED	8	8	6	23
Overall Study NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Mild Hepatic Impairment n=8 Participants Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Moderate Hepatic Impairment n=8 Participants Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Severe Hepatic Impairment n=6 Participants Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function n=23 Participants Participants with normal hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Total n=45 Participants Total of all reporting groups
Age, Continuous	59.5 Years STANDARD_DEVIATION 7.3 • n=5 Participants	57.8 Years STANDARD_DEVIATION 3.8 • n=7 Participants	51.2 Years STANDARD_DEVIATION 4.4 • n=5 Participants	56.2 Years STANDARD_DEVIATION 5.2 • n=4 Participants	56.4 Years STANDARD_DEVIATION 5.7 • n=21 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	5 Participants n=4 Participants	10 Participants n=21 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants	18 Participants n=4 Participants	35 Participants n=21 Participants

PRIMARY outcome

Timeframe: Day 1 to Day 8

Population: Pharmacokinetics (PK) set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations.

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

Outcome measures

Measure	Mild Hepatic Impairment n=8 Participants Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Mild Hepatic Function n=8 Participants 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 n=8 Participants Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Moderate Hepatic Function. n=8 Participants 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 n=6 Participants Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Severe Hepatic Function. n=6 Participants 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.
Unbound Brexpiprazole Area Under the Concentration Time Curve (AUC) Calculated to the Last Observable Concentration at Time t (AUCt,u)	5.95 nanograms.hours/mL (ng*h/mL) Standard Deviation 2.58	4.87 nanograms.hours/mL (ng*h/mL) Standard Deviation 1.78	5.41 nanograms.hours/mL (ng*h/mL) Standard Deviation 1.37	4.28 nanograms.hours/mL (ng*h/mL) Standard Deviation 1.95	3.27 nanograms.hours/mL (ng*h/mL) Standard Deviation 0.93	3.63 nanograms.hours/mL (ng*h/mL) Standard Deviation 1.54

PRIMARY outcome

Timeframe: Day 1 to Day 8

Population: PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations.

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

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

Outcome measures

Measure	Mild Hepatic Impairment n=7 Participants Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Mild Hepatic Function n=6 Participants 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 n=7 Participants Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Moderate Hepatic Function. n=7 Participants 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 n=3 Participants Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Severe Hepatic Function. n=5 Participants 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.
Unbound Brexpiprazole AUC Calculated From Time Zero to Infinity (AUC∞,u)	8.59 ng*h/mL Standard Deviation 5.29	5.85 ng*h/mL Standard Deviation 3.11	8.50 ng*h/mL Standard Deviation 2.17	5.62 ng*h/mL Standard Deviation 3.13	3.49 ng*h/mL Standard Deviation 0.848	3.36 ng*h/mL Standard Deviation 0.871

PRIMARY outcome

Timeframe: Day 1 to Day 8

Population: PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations.

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

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

Outcome measures

Measure	Mild Hepatic Impairment n=8 Participants Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Mild Hepatic Function n=8 Participants 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 n=8 Participants Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Moderate Hepatic Function. n=8 Participants 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 n=6 Participants Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Severe Hepatic Function. n=6 Participants 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.
Unbound Maximum Plasma Concentration of Brexpiprazole (Cmax,u)	0.104 ng/mL Standard Deviation 0.0259	0.114 ng/mL Standard Deviation 0.0270	0.0648 ng/mL Standard Deviation 0.0143	0.0779 ng/mL Standard Deviation 0.0224	0.0392 ng/mL Standard Deviation 0.0105	0.0760 ng/mL Standard Deviation 0.0258

SECONDARY outcome

Timeframe: Day 1 to Day 8

Population: PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations.

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

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

Outcome measures

Measure	Mild Hepatic Impairment n=8 Participants Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Mild Hepatic Function n=8 Participants 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 n=8 Participants Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Moderate Hepatic Function. n=8 Participants 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 n=6 Participants Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Severe Hepatic Function. n=6 Participants 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.
Area Under the Curve of Brexpiprazole Calculated to the Last Observable Concentration at Time t (AUCt)	1271 ng*h/mL Standard Deviation 569	1145 ng*h/mL Standard Deviation 539	1213 ng*h/mL Standard Deviation 405	1048 ng*h/mL Standard Deviation 422	622 ng*h/mL Standard Deviation 163	817 ng*h/mL Standard Deviation 306

SECONDARY outcome

Timeframe: Day 1 to Day 8

Population: PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations.

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

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

The AUC∞ was estimated using the linear trapezoidal rule

Outcome measures

Measure	Mild Hepatic Impairment n=7 Participants Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Mild Hepatic Function n=6 Participants 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 n=7 Participants Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Moderate Hepatic Function. n=7 Participants 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 n=3 Participants Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Severe Hepatic Function. n=5 Participants 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.
Area Under the Concentration Time Curve of Brexpiprazole From Time Zero to Infinity (AUC∞)	1827 ng*h/mL Standard Deviation 1103	1393 ng*h/mL Standard Deviation 881	1960 ng*h/mL Standard Deviation 579	1345 ng*h/mL Standard Deviation 697	831 ng*h/mL Standard Deviation 234	788 ng*h/mL Standard Deviation 230

SECONDARY outcome

Timeframe: Day 1 to Day 8

Population: PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations.

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

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

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

Outcome measures

Measure	Mild Hepatic Impairment n=8 Participants Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Mild Hepatic Function n=8 Participants 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 n=8 Participants Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Moderate Hepatic Function. n=8 Participants 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 n=6 Participants Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Severe Hepatic Function. n=6 Participants 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.
Maximum Plasma Concentration of Brexpiprazole (Cmax)	22.9 ng/mL Standard Deviation 7.60	26.7 ng/mL Standard Deviation 9.09	14.6 ng/mL Standard Deviation 4.63	19.3 ng/mL Standard Deviation 4.98	7.65 ng/mL Standard Deviation 2.69	17.7 ng/mL Standard Deviation 7.38

SECONDARY outcome

Timeframe: Day 1 to Day 8

Population: PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations.

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

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

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

Outcome measures

Measure	Mild Hepatic Impairment n=8 Participants Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Mild Hepatic Function n=8 Participants 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 n=8 Participants Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Moderate Hepatic Function. n=8 Participants 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 n=6 Participants Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Severe Hepatic Function. n=6 Participants 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.
Time to Cmax of Brexiprazole (Tmax)	3.50 h Interval 1.0 to 5.0	3.50 h Interval 2.0 to 5.0	4.50 h Interval 3.0 to 24.0	4.50 h Interval 1.0 to 6.0	5.00 h Interval 4.0 to 24.0	5.00 h Interval 2.0 to 6.0

SECONDARY outcome

Timeframe: Day 1 to Day 8

Population: PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations.

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.

Outcome measures

Measure	Mild Hepatic Impairment n=7 Participants Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Mild Hepatic Function n=6 Participants 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 n=7 Participants Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Moderate Hepatic Function. n=6 Participants 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 n=3 Participants Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Severe Hepatic Function. n=5 Participants 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.
Apparent Clearance of Brexpiprazole From Plasma After Extravascular Administration (CL/F)	24.5 mL/h/kg Standard Deviation 28.2	25.4 mL/h/kg Standard Deviation 12.3	13.8 mL/h/kg Standard Deviation 2.72	26.0 mL/h/kg Standard Deviation 19.2	28.2 mL/h/kg Standard Deviation 6.70	34.2 mL/h/kg Standard Deviation 16.3

SECONDARY outcome

Timeframe: Day 1 to Day 8

Population: PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations.

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.

Outcome measures

Measure	Mild Hepatic Impairment n=8 Participants Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Mild Hepatic Function n=8 Participants 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 n=8 Participants Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Moderate Hepatic Function. n=8 Participants 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 n=6 Participants Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Severe Hepatic Function. n=6 Participants 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.
Unbound Fraction of Brexpiprazole in Plasma (fu)	0.472 % unbound drug in the urine Standard Deviation 0.0840	0.451 % unbound drug in the urine Standard Deviation 0.112	0.462 % unbound drug in the urine Standard Deviation 0.0786	0.400 % unbound drug in the urine Standard Deviation 0.0442	0.544 % unbound drug in the urine Standard Deviation 0.186	0.450 % unbound drug in the urine Standard Deviation 0.0795

SECONDARY outcome

Timeframe: Day 1 to Day 8

Population: PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations.

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

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

Outcome measures

Measure	Mild Hepatic Impairment n=7 Participants Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Mild Hepatic Function n=6 Participants 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 n=7 Participants Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Moderate Hepatic Function. n=7 Participants 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 n=3 Participants Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Severe Hepatic Function. n=5 Participants 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.
Apparent Unbound Clearance of Brexpiprazole From Plasma After Extravascular Administration (CLu/F)	5674 mL/h/kg Standard Deviation 7165	5730 mL/h/kg Standard Deviation 2944	3115 mL/h/kg Standard Deviation 494	6768 mL/h/kg Standard Deviation 5833	6598 mL/h/kg Standard Deviation 1182	7697 mL/h/kg Standard Deviation 2653

SECONDARY outcome

Timeframe: Day 1 to Day 8

Population: PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations.

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

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

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

Outcome measures

Measure	Mild Hepatic Impairment n=7 Participants Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Mild Hepatic Function n=6 Participants 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 n=7 Participants Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Moderate Hepatic Function. n=7 Participants 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 n=3 Participants Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Severe Hepatic Function. n=5 Participants 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.
Terminal-phase Elimination Half-life of Brexpiprazole (t1/2,z)	103 h Standard Deviation 51.1	64.7 h Standard Deviation 24.6	116 h Standard Deviation 25.8	64.2 h Standard Deviation 26.2	81.1 h Standard Deviation 17.1	51.4 h Standard Deviation 8.21

SECONDARY outcome

Timeframe: Day 1 to Day 8

Population: PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations.

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

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

Outcome measures

Measure	Mild Hepatic Impairment n=8 Participants Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Mild Hepatic Function n=8 Participants 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 n=8 Participants Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Moderate Hepatic Function. n=8 Participants 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 n=6 Participants Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Severe Hepatic Function. n=6 Participants 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.
Renal Clearance (CLr) of Brexipiprazole	0.0468 mL/h/kg Standard Deviation 0.0353	0.0263 mL/h/kg Standard Deviation 0.0244	0.0360 mL/h/kg Standard Deviation 0.0286	0.0422 mL/h/kg Standard Deviation 0.0383	0.0402 mL/h/kg Standard Deviation 0.0872	0.0193 mL/h/kg Standard Deviation 0.0203

SECONDARY outcome

Timeframe: Day 1 to Day 8

Population: PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations.

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

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

Outcome measures

Measure	Mild Hepatic Impairment n=8 Participants Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Mild Hepatic Function n=8 Participants 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 n=8 Participants Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Moderate Hepatic Function. n=8 Participants 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 n=6 Participants Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Severe Hepatic Function. n=6 Participants 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.
Cumulative Amount of Brexpiprazole Excreted Into the Urine (Ae,u)	4511 ng Standard Deviation 3808	1854 ng Standard Deviation 1500	3522 ng Standard Deviation 2740	3837 ng Standard Deviation 3358	2090 ng Standard Deviation 4699	1326 ng Standard Deviation 1427

SECONDARY outcome

Timeframe: Day 1 to Day 8

Population: PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations.

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

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

Outcome measures

Measure	Mild Hepatic Impairment n=8 Participants Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Mild Hepatic Function n=8 Participants 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 n=8 Participants Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Moderate Hepatic Function. n=8 Participants 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 n=6 Participants Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Severe Hepatic Function. n=6 Participants 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.
Fraction of Systemically Available Brexpiprazole Excreted Into the Urine (fe,u)	0.226 % of drug in urine Standard Deviation 0.190	0.0927 % of drug in urine Standard Deviation 0.0750	0.176 % of drug in urine Standard Deviation 0.137	0.192 % of drug in urine Standard Deviation 0.168	0.104 % of drug in urine Standard Deviation 0.235	0.0663 % of drug in urine Standard Deviation 0.0713

SECONDARY outcome

Timeframe: Day 1 to Day 8

Population: PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations.

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

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

The AUCt was estimated using the linear trapezoidal rule.

Outcome measures

Measure	Mild Hepatic Impairment n=8 Participants Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Mild Hepatic Function n=8 Participants 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 n=8 Participants Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Moderate Hepatic Function. n=8 Participants 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 n=6 Participants Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Severe Hepatic Function. n=6 Participants 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.
AUCt for DM-3411 Metabolite	380 ng*h/mL Standard Deviation 195	683 ng*h/mL Standard Deviation 246	284 ng*h/mL Standard Deviation 164	486 ng*h/mL Standard Deviation 263	151 ng*h/mL Standard Deviation 51.4	479 ng*h/mL Standard Deviation 226

SECONDARY outcome

Timeframe: Day 1 to Day 8

Population: PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations.

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.

Outcome measures

Measure	Mild Hepatic Impairment n=5 Participants Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Mild Hepatic Function n=6 Participants 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 n=6 Participants Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Moderate Hepatic Function. n=6 Participants 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 n=4 Participants Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Severe Hepatic Function. n=3 Participants 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.
AUC∞ for DM-3411 Metabolite	489 ng*h/mL Standard Deviation 210	692 ng*h/mL Standard Deviation 259	382 ng*h/mL Standard Deviation 262	530 ng*h/mL Standard Deviation 211	187 ng*h/mL Standard Deviation 67.2	329 ng*h/mL Standard Deviation 167

SECONDARY outcome

Timeframe: Day 1 to Day 8

Population: PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations.

Blood samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose/ET. Cmax is the highest measured concentration of the metabolite during the dosing interval.

Outcome measures

Measure	Mild Hepatic Impairment n=8 Participants Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Mild Hepatic Function n=8 Participants 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 n=8 Participants Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Moderate Hepatic Function. n=8 Participants 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 n=6 Participants Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Severe Hepatic Function. n=6 Participants 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.
Cmax for DM-3411 Metabolite	6.49 ng/mL Standard Deviation 5.13	10.5 ng/mL Standard Deviation 4.26	3.19 ng/mL Standard Deviation 1.56	7.25 ng/mL Standard Deviation 4.83	2.15 ng/mL Standard Deviation 0.880	7.13 ng/mL Standard Deviation 3.73

SECONDARY outcome

Timeframe: Day 1 to Day 8

Population: PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations.

Blood samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose/ET. Tmax is the time taken to reach highest measured concentration of the metabolite during the dosing interval.

Outcome measures

Measure	Mild Hepatic Impairment n=8 Participants Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Mild Hepatic Function n=8 Participants 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 n=8 Participants Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Moderate Hepatic Function. n=8 Participants 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 n=6 Participants Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Severe Hepatic Function. n=6 Participants 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.
Tmax for DM-3411 Metabolite	5.00 h Interval 2.0 to 24.0	6.00 h Interval 5.0 to 24.0	5.00 h Interval 2.0 to 24.0	7.00 h Interval 2.0 to 24.0	4.5 h Interval 3.0 to 24.0	6.00 h Interval 5.0 to 16.0

SECONDARY outcome

Timeframe: Day 1 to Day 8

Population: PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations.

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

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

Outcome measures

Measure	Mild Hepatic Impairment n=5 Participants Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Mild Hepatic Function n=6 Participants 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 n=6 Participants Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Moderate Hepatic Function. n=6 Participants 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 n=4 Participants Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Severe Hepatic Function. n=3 Participants 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.
t1/2,z for DM-3411 Metabolite	78.8 h Standard Deviation 37.6	59.7 h Standard Deviation 15.7	87.2 h Standard Deviation 45.7	62.0 h Standard Deviation 26.4	84.6 h Standard Deviation 12.0	56.1 h Standard Deviation 8.25

SECONDARY outcome

Timeframe: Day 1 to Day 8

Population: PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations.

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

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

Outcome measures

Measure	Mild Hepatic Impairment n=8 Participants Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Mild Hepatic Function n=8 Participants 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 n=8 Participants Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Moderate Hepatic Function. n=8 Participants 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 n=6 Participants Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Severe Hepatic Function. n=6 Participants 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.
Ae,u for DM-3411 Metabolite	67086 ng Standard Deviation 25276	81148 ng Standard Deviation 23188	68413 ng Standard Deviation 16993	71353 ng Standard Deviation 41630	48190 ng Standard Deviation 14756	83604 ng Standard Deviation 34907

SECONDARY outcome

Timeframe: Day 1 to Day 8

Population: PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations.

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

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

Outcome measures

Measure	Mild Hepatic Impairment n=8 Participants Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Mild Hepatic Function n=8 Participants 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 n=8 Participants Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Moderate Hepatic Function. n=8 Participants 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 n=6 Participants Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Severe Hepatic Function. n=6 Participants 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.
fe,u for DM-3411 Metabolite	3.23 % metabolite excreted in urine Standard Deviation 1.22	3.91 % metabolite excreted in urine Standard Deviation 1.12	3.30 % metabolite excreted in urine Standard Deviation 0.819	3.44 % metabolite excreted in urine Standard Deviation 2.01	2.32 % metabolite excreted in urine Standard Deviation 0.712	4.03 % metabolite excreted in urine Standard Deviation 1.68

SECONDARY outcome

Timeframe: Day 1 to Day 8

Population: PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations.

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

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

Outcome measures

Measure	Mild Hepatic Impairment n=8 Participants Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Mild Hepatic Function n=8 Participants 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 n=8 Participants Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Moderate Hepatic Function. n=8 Participants 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 n=6 Participants Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Severe Hepatic Function. n=6 Participants 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.
CLr for DM-3411 Metabolite	2.67 mL/h/kg Standard Deviation 1.31	1.83 mL/h/kg Standard Deviation 0.828	3.96 mL/h/kg Standard Deviation 2.32	1.90 mL/h/kg Standard Deviation 0.568	4.08 mL/h/kg Standard Deviation 1.68	2.33 mL/h/kg Standard Deviation 1.01

SECONDARY outcome

Timeframe: From the time the Informed Consent Form was signed, throughout the 8 day study up to 30 days after study drug administration.

Population: Participants who received at least one dose of study drug were included in the safety analysis.

AEs were captured for all participants from the time the ICF was signed until the end of the study

Outcome measures

Measure	Mild Hepatic Impairment n=8 Participants Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Mild Hepatic Function n=8 Participants 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 n=6 Participants Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Moderate Hepatic Function. n=23 Participants Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each participant with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.	Severe Hepatic Impairment Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Severe Hepatic Function. Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each participant with normal hepatic function was matched to a participant with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.
Number of Adverse Events (AEs) Reported Adverse events	3 Events	5 Events	1 Events	8 Events	—	—
Number of Adverse Events (AEs) Reported Treatment emergent adverse events	3 Events	5 Events	1 Events	6 Events	—	—
Number of Adverse Events (AEs) Reported Serious adverse events	0 Events	0 Events	0 Events	0 Events	—	—

SECONDARY outcome

Timeframe: Day -1 to Day 8

Population: 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.

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

Outcome measures

Measure	Mild Hepatic Impairment n=8 Participants Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Mild Hepatic Function n=8 Participants 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 n=6 Participants Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Moderate Hepatic Function. n=23 Participants Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each participant with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.	Severe Hepatic Impairment Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Severe Hepatic Function. Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each participant with normal hepatic function was matched to a participant with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.
Number of Participants With Changes From Baseline in Vital Signs Parameters.	0 Participants	0 Participants	0 Participants	0 Participants	—	—

SECONDARY outcome

Timeframe: Day-1 to Day 8

Population: 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.

Electrocardiograms were performed at Screening, Day -1, and Day 1 at predose (in triplicate; within 45 minutes prior to dosing), and 2, 4, 6, 8, 12, 24, 72, 120, and 168/ET hours postdose. Standard 12-lead ECGs were performed after the subject was supine and at rest for ≥ 10 minutes prior to the ECG.

Outcome measures

Measure	Mild Hepatic Impairment n=8 Participants Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Mild Hepatic Function n=8 Participants 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 n=6 Participants Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Moderate Hepatic Function. n=23 Participants Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each participant with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.	Severe Hepatic Impairment Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Severe Hepatic Function. Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each participant with normal hepatic function was matched to a participant with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.
Number of Participants With Changes From Baseline in Electrocardiogram (ECG) Parameters.	0 Participants	0 Participants	0 Participants	0 Participants	—	—

SECONDARY outcome

Timeframe: Day -1 to Day 8

Population: 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.

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.

Outcome measures

Measure	Mild Hepatic Impairment n=8 Participants Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Mild Hepatic Function n=8 Participants 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 n=6 Participants Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Moderate Hepatic Function. n=23 Participants Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each participant with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.	Severe Hepatic Impairment Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Severe Hepatic Function. Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each participant with normal hepatic function was matched to a participant with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.
Number of Participants With Changes From Baseline in Serum Chemistry, Hematology and Urinalysis Parameters.	0 Participant	0 Participant	0 Participant	0 Participant	—	—

SECONDARY outcome

Timeframe: Day 1, Day 4, Day 7

Population: 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.

The Baseline version of the C-SSRS was administered at Screening. The Since Last Visit version of the C-SSRS was administered on Day 1 at predose and on Days 4 and 7.

Outcome measures

Measure	Mild Hepatic Impairment n=8 Participants Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Mild Hepatic Function n=8 Participants 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 n=6 Participants Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Moderate Hepatic Function. n=23 Participants Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each participant with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.	Severe Hepatic Impairment Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function Matched to Severe Hepatic Function. Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each participant with normal hepatic function was matched to a participant with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled.
Incidence of Suicidality, Suicidal Behaviour or Suicidal Ideation as Measured by the Columbia-Suicide Severity Rating Scale (C-SSRS)	0 Participants	0 Participants	0 Participants	0 Participants	—	—

Adverse Events

Mild Hepatic Impairment

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Moderate Hepatic Impairment

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Severe Hepatic Impairment

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Normal Hepatic Function

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Mild Hepatic Impairment n=8 participants at risk Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Moderate Hepatic Impairment n=8 participants at risk Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Severe Hepatic Impairment n=6 participants at risk Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.	Normal Hepatic Function n=23 participants at risk Participants with normal hepatic function (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg.
Gastrointestinal disorders Diarrhoea	0.00% 0/8 • 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. 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.	12.5% 1/8 • 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. 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.	0.00% 0/6 • 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. 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.	0.00% 0/23 • 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. 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.
General disorders Fatigue	12.5% 1/8 • 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. 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.	12.5% 1/8 • 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. 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.	0.00% 0/6 • 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. 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.	0.00% 0/23 • 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. 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.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/8 • 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. 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.	0.00% 0/8 • 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. 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.	0.00% 0/6 • 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. 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.	4.3% 1/23 • 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. 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.
Nervous system disorders Dizziness	12.5% 1/8 • 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. 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.	0.00% 0/8 • 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. 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.	0.00% 0/6 • 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. 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.	0.00% 0/23 • 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. 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.
Nervous system disorders Headache	12.5% 1/8 • 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. 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.	12.5% 1/8 • 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. 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.	16.7% 1/6 • 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. 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.	17.4% 4/23 • 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. 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.
Nervous system disorders Somnolence	0.00% 0/8 • 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. 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.	12.5% 1/8 • 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. 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.	0.00% 0/6 • 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. 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.	4.3% 1/23 • 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. 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.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/8 • 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. 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.	12.5% 1/8 • 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. 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.	0.00% 0/6 • 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. 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.	0.00% 0/23 • 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. 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.

Additional Information

Global Medical Affairs

Otsuka Pharmaceutical Development and Commercialization, Inc.

Phone: 800-562-3974

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place