A Study Evaluating the of OPC-34712 in Subjects With Normal Hepatic Function and Hepatically Impaired Subjects
Sponsor
Otsuka Pharmaceutical Development & Commercialization, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT01299454
Collaborator
(none)
45
3
4
7
15
2.2
Study Details
Study Description
Brief Summary
The purpose of this study is to evaluate how much of the investigational product gets into the blood stream and how long the body takes to get rid of it when given to subjects with a range of liver impairment compared to subjects with normal liver function.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Detailed Description
This is a multi-center, open-label, parallel-arm study in 1 group of subjects with normal hepatic function and 3 groups of subjects with varying degrees of hepatic impairment (mild, moderate, and severe). Subjects will be confined to the clinic from Day -1 to Day 8. Subjects will be contacted via telephone 30 days (+ 2 days) after the last dose of study medication to assess any new or ongoing AEs and to record concomitant medications. All groups will receive a single oral 2-mg OPC-34712 dose on Day 1 with 240 mL room temperature still water. Subjects will be administered the OPC-34712 dose in the fasted state (at least 8 hours of fasting) and no food will be allowed for 4 hours postdose.
Study Design
Study Type:
Interventional
Actual Enrollment
:
45 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Single-dose, Open-label, Parallel Group, Matched Study Evaluating the Pharmacokinetics of Oral OPC-34712 Tablet in Subjects With Normal Hepatic Function and Hepatically Impaired Subjects
Study Start Date
:
Dec 1, 2010
Actual Primary Completion Date
:
Jun 1, 2011
Actual Study Completion Date
:
Jul 1, 2011
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Normal
|
Drug: OPC-34712
All groups will receive a single oral 2-mg OPC-34712 dose on Day 1 with 240 mL room temperature still water. Subjects will be administered the OPC-34712 dose in the fasted state (at least 8 hours of fasting) and no food will be allowed for 4 hours postdose. Water will be restricted as part of the dosing procedure from 1 hour prior to dosing and 2 hours post-dose.
|
| Active Comparator: Mild
|
Drug: OPC-34712
All groups will receive a single oral 2-mg OPC-34712 dose on Day 1 with 240 mL room temperature still water. Subjects will be administered the OPC-34712 dose in the fasted state (at least 8 hours of fasting) and no food will be allowed for 4 hours postdose. Water will be restricted as part of the dosing procedure from 1 hour prior to dosing and 2 hours post-dose.
|
| Active Comparator: Moderate
|
Drug: OPC-34712
All groups will receive a single oral 2-mg OPC-34712 dose on Day 1 with 240 mL room temperature still water. Subjects will be administered the OPC-34712 dose in the fasted state (at least 8 hours of fasting) and no food will be allowed for 4 hours postdose. Water will be restricted as part of the dosing procedure from 1 hour prior to dosing and 2 hours post-dose.
|
| Active Comparator: Severe
|
Drug: OPC-34712
All groups will receive a single oral 2-mg OPC-34712 dose on Day 1 with 240 mL room temperature still water. Subjects will be administered the OPC-34712 dose in the fasted state (at least 8 hours of fasting) and no food will be allowed for 4 hours postdose. Water will be restricted as part of the dosing procedure from 1 hour prior to dosing and 2 hours post-dose.
|
Outcome Measures
Primary Outcome Measures
- Unbound Brexpiprazole Area Under the Concentration Time Curve (AUC) Calculated to the Last Observable Concentration at Time t (AUCt,u) [Day 1 to Day 8]
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).
- Unbound Brexpiprazole AUC Calculated From Time Zero to Infinity (AUC∞,u) [Day 1 to Day 8]
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 - ∞).
- Unbound Maximum Plasma Concentration of Brexpiprazole (Cmax,u) [Day 1 to Day 8]
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.
Secondary Outcome Measures
- Area Under the Curve of Brexpiprazole Calculated to the Last Observable Concentration at Time t (AUCt) [Day 1 to Day 8]
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.
- Area Under the Concentration Time Curve of Brexpiprazole From Time Zero to Infinity (AUC∞) [Day 1 to Day 8]
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
- Maximum Plasma Concentration of Brexpiprazole (Cmax) [Day 1 to Day 8]
Blood samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose/ET. Cmax is the highest measured concentration of the drug during the dosing interval. Actual blood sample times were used for PK calculations. Values for Cmax and tmax were determined directly from the observed data.
- Time to Cmax of Brexiprazole (Tmax) [Day 1 to Day 8]
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.
- Apparent Clearance of Brexpiprazole From Plasma After Extravascular Administration (CL/F) [Day 1 to Day 8]
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.
- Unbound Fraction of Brexpiprazole in Plasma (fu) [Day 1 to Day 8]
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.
- Apparent Unbound Clearance of Brexpiprazole From Plasma After Extravascular Administration (CLu/F) [Day 1 to Day 8]
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).
- Terminal-phase Elimination Half-life of Brexpiprazole (t1/2,z) [Day 1 to Day 8]
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.
- Renal Clearance (CLr) of Brexipiprazole [Day 1 to Day 8]
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.
- Cumulative Amount of Brexpiprazole Excreted Into the Urine (Ae,u) [Day 1 to Day 8]
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
- Fraction of Systemically Available Brexpiprazole Excreted Into the Urine (fe,u) [Day 1 to Day 8]
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.
- AUCt for DM-3411 Metabolite [Day 1 to Day 8]
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.
- AUC∞ for DM-3411 Metabolite [Day 1 to Day 8]
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.
- Cmax for DM-3411 Metabolite [Day 1 to Day 8]
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.
- Tmax for DM-3411 Metabolite [Day 1 to Day 8]
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.
- t1/2,z for DM-3411 Metabolite [Day 1 to Day 8]
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.
- Ae,u for DM-3411 Metabolite [Day 1 to Day 8]
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.
- fe,u for DM-3411 Metabolite [Day 1 to Day 8]
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.
- CLr for DM-3411 Metabolite [Day 1 to Day 8]
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.
- Number of Adverse Events (AEs) Reported [From the time the Informed Consent Form was signed, throughout the 8 day study up to 30 days after study drug administration.]
AEs were captured for all participants from the time the ICF was signed until the end of the study
- Number of Participants With Changes From Baseline in Vital Signs Parameters. [Day -1 to Day 8]
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
- Number of Participants With Changes From Baseline in Electrocardiogram (ECG) Parameters. [Day-1 to Day 8]
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.
- Number of Participants With Changes From Baseline in Serum Chemistry, Hematology and Urinalysis Parameters. [Day -1 to Day 8]
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.
- Incidence of Suicidality, Suicidal Behaviour or Suicidal Ideation as Measured by the Columbia-Suicide Severity Rating Scale (C-SSRS) [Day 1, Day 4, Day 7]
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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
Inclusion Criteria:
-
Males and females of non-childbearing potential ≥ 18 years of age
-
Body weight within ± 30% of ideal body weight as defined in the 1983 Metropolitan Height and Weight Tables. Minimum body weight no less than 50 kg.
-
Able to provide written, informed consent.
-
Male and female subjects who are surgically sterile; female subjects who have been postmenopausal for at least 12 consecutive months; or male subjects who agree to remain abstinent or to practice double-barrier forms of birth control and refrain from sperm donation from Screening through 90 days from the last dose of study medication.
Inclusion Criteria for Hepatically Impaired Subjects Only:
-
Hepatically impaired subjects with creatinine clearance (CLcr) > 30 mL/min.
-
Subjects with hepatic impairment should have relatively stable hepatic function for the duration of the study, and otherwise be in generally good health.
-
A clinical diagnosis of hepatic cirrhosis based on biopsy and/or clinical criteria.
-
Child-Pugh Class A (mild), B (moderate), or C (severe)
-
Hepatically impaired subjects may be taking medications, which in the opinion of the clinical investigator and sponsor, are believed to be therapeutic for the subjects.
-
Hepatically impaired subjects may have a history of or current hepatitis or be carriers of hepatitis B surface antigen (HBsAg) and/or hepatitis C antibodies (anti-HC).
Inclusion Criteria for Subjects with Normal Hepatic Function Only
-
Must be in good health as determined by medical history, physical examination, ECG, serum/urine biochemistry, hematology, and serology tests.
-
Normal renal function as evidenced by CLcr that is within 20% of normal for the age, sex, and weight of the individual.
Exclusion Criteria:
-
History of drug and/or alcohol abuse within 2 years prior to Screening.
-
History of acquired immunodeficiency syndrome or human immunodeficiency virus (HIV) antibodies.
-
History of any significant drug allergy or known or suspected hypersensitivity.
-
A positive urine alcohol test and/or urine drug screen for substance of abuse at Screening or upon admission to the study center.
-
Subjects having taken an investigational drug within 30 days preceding study entry.
-
Any history of significant bleeding or hemorrhagic tendencies. Subjects with a history of bleeding tendencies secondary to hepatic impairment will not be excluded.
-
A history of difficulty in donating blood.
-
The donation of blood or plasma within 30 days prior to dosing.
-
Consumption of alcohol and/or food and beverages containing methylxanthines, grapefruit, grapefruit juice, Seville oranges, or Seville orange juice within 72 hours prior to dosing.
-
Exposure to any substances known to stimulate hepatic microsomal enzymes within 30 days prior to Screening through the end of the study.
-
Subjects who have supine, sitting, or standing blood pressure, after resting for ≥ 3 minutes, higher than 140/90 mmHg or lower than 100/50 mmHg.
-
Subjects who have a supine pulse rate, after resting for ≥ 3 minutes, outside the range of 40 to 90 bpm.
-
Previous exposure to OPC-34712.
-
Subjects who are pregnant or breastfeeding.
-
Subjects with a QTcF interval ≥ 450 msec.
-
Subjects with PT greater than 2 times control. Subjects with hepatic impairment with prolonged PT will be excluded based on the PI's discretion.
-
Subjects with hepatic carcinoma or porto-hepatic shunts that have been surgically created or planted.
-
Partial thromboplastin time > 70 seconds.
Exclusion Criteria for Hepatically Impaired Subjects Only:
-
History of serious mental disorder including subjects who are pre-encephalopathic or encephalopathic as assessed by the Child-Pugh score and/or the PI's judgment.
-
Major surgery of the digestive tract.
Exclusion Criteria for Subjects with Normal Hepatic Function Only:
-
Clinically significant abnormality in past medical history.
-
History of or current hepatitis, or carriers of HBsAg and/or anti-HC.
-
Use of prescription, over-the-counter, herbal medication or vitamin supplements within 14 days prior to dosing and antibiotics within 30 days prior to dosing.
-
History of serious mental disorders.
-
Major surgery of the digestive tract (excluding appendectomy).
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Study Site | Miami | Florida | United States | 33014 |
| 2 | Study Site | Minneapolis | Minnesota | United States | 55404 |
| 3 | Study Site | San Antonio | Texas | United States | 78212 |
Sponsors and Collaborators
- Otsuka Pharmaceutical Development & Commercialization, Inc.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier:
NCT01299454
Other Study ID Numbers:
- 331-09-225
First Posted:
Feb 18, 2011
Last Update Posted:
Oct 20, 2015
Last Verified:
Sep 1, 2015
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | 81 participants were screened; of these 45 participants were enrolled recruited at 3 study sites in the United States (US). |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Mild Hepatic Impairment | Moderate Hepatic Impairment | Severe Hepatic Impairment | Normal Hepatic Function |
|---|---|---|---|---|
| Arm/Group Description | Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 milligrams (mg). | Participants with moderate hepatic impairment (Child-Pugh classification scheme)received a single dose of oral brexpiprazole 2 mg. | Participants with severe hepatic impairment (based on Child-Pugh classification scheme) received a single dose of oral brexpiprazole 2 mg. | Participants with normal hepatic function (based on Child-Pugh classification scheme) received a single dose of oral brexpiprazole 2 mg. |
| Period Title: Overall Study | ||||
| STARTED | 8 | 8 | 6 | 23 |
| COMPLETED | 8 | 8 | 6 | 23 |
| NOT COMPLETED | 0 | 0 | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Mild Hepatic Impairment | Moderate Hepatic Impairment | Severe Hepatic Impairment | Normal Hepatic Function | Total |
|---|---|---|---|---|---|
| Arm/Group Description | Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Total of all reporting groups |
| Overall Participants | 8 | 8 | 6 | 23 | 45 |
| Age (Years) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [Years] |
59.5
(7.3)
|
57.8
(3.8)
|
51.2
(4.4)
|
56.2
(5.2)
|
56.4
(5.7)
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
3
37.5%
|
2
25%
|
0
0%
|
5
21.7%
|
10
22.2%
|
| Male |
5
62.5%
|
6
75%
|
6
100%
|
18
78.3%
|
35
77.8%
|
Outcome Measures
| Title | Unbound Brexpiprazole Area Under the Concentration Time Curve (AUC) Calculated to the Last Observable Concentration at Time t (AUCt,u) |
|---|---|
| Description | Blood samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose/Early termination (ET). |
| Time Frame | Day 1 to Day 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetics (PK) set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations. |
| Arm/Group Title | Mild Hepatic Impairment | Normal Hepatic Function Matched to Mild Hepatic Function | Moderate Hepatic Impairment | Normal Hepatic Function Matched to Moderate Hepatic Function. | Severe Hepatic Impairment | Normal Hepatic Function Matched to Severe Hepatic Function. |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each participant with normal hepatic function was matched to a participant with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. | Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each participant with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. | Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each participant with normal hepatic function was matched to a participant with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. |
| Measure Participants | 8 | 8 | 8 | 8 | 6 | 6 |
| Mean (Standard Deviation) [nanograms.hours/mL (ng*h/mL)] |
5.95
(2.58)
|
4.87
(1.78)
|
5.41
(1.37)
|
4.28
(1.95)
|
3.27
(0.93)
|
3.63
(1.54)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Mild Hepatic Impairment, Normal Hepatic Function Matched to Mild Hepatic Function |
|---|---|---|
| Comments | The primary comparison was each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the primary PK parameters between each hepatic disease group and the control group, the 90% confidence interval (CI) for the difference in the means of the log-transformed data was calculated using a mixed effect analysis of variance. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normal-theory CIs, this approach was equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 1.166 | |
| Confidence Interval |
(2-Sided) 90% 0.776 to 1.751 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Due to the nature of the normal-theory CIs, this approach is equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Moderate Hepatic Impairment, Normal Hepatic Function Matched to Moderate Hepatic Function. |
|---|---|---|
| Comments | The primary comparison was each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the primary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the log-transformed data was calculated using a mixed effect analysis of variance. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normal-theory CIs, this approach was equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 1.375 | |
| Confidence Interval |
(2-Sided) 90% 0.915 to 2.066 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Due to the nature of the normal-theory CIs, this approach is equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Severe Hepatic Impairment, Normal Hepatic Function Matched to Severe Hepatic Function. |
|---|---|---|
| Comments | The primary comparison was each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the primary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the log-transformed data was calculated using a mixed effect analysis of variance. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normal-theory CIs, this approach was equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 0.929 | |
| Confidence Interval |
(2-Sided) 90% 0.581 to 1.488 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Due to the nature of the normal-theory CIs, this approach is equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance. | |
| Title | Unbound Brexpiprazole AUC Calculated From Time Zero to Infinity (AUC∞,u) |
|---|---|
| Description | Blood samples were taken at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose/ET. AUC (0 - ∞)= AUC from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞). |
| Time Frame | Day 1 to Day 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations. |
| Arm/Group Title | Mild Hepatic Impairment | Normal Hepatic Function Matched to Mild Hepatic Function. | Moderate Hepatic Impairment. | Normal Hepatic Function Matched to Moderate Hepatic Function. | Severe Hepatic Function | Normal Hepatic Function Matched to Severe Hepatic Function. |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg | Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each participant with normal hepatic function was matched to a participant with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. | Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each participant with normal hepatic function was matched to a participant with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. | Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each participant with normal hepatic function was matched to a participant with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled |
| Measure Participants | 7 | 6 | 7 | 7 | 3 | 5 |
| Mean (Standard Deviation) [ng*h/mL] |
8.59
(5.29)
|
5.85
(3.11)
|
8.50
(2.17)
|
5.62
(3.13)
|
3.49
(0.848)
|
3.36
(0.871)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Mild Hepatic Impairment, Normal Hepatic Function Matched to Mild Hepatic Function |
|---|---|---|
| Comments | The primary comparison was each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the primary PK parameters between each hepatic disease group and the control group, the 90% confidence interval (CI) for the difference in the means of the log-transformed data was calculated using a mixed effect analysis of variance. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normal-theory CIs, this approach was equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometic Mean Ratio |
| Estimated Value | 1.255 | |
| Confidence Interval |
(2-Sided) 90% 0.702 to 2.244 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Due to the nature of the normal-theory CIs, this approach is equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Moderate Hepatic Impairment, Normal Hepatic Function Matched to Moderate Hepatic Function. |
|---|---|---|
| Comments | The primary comparison was each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the primary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the log-transformed data was calculated using a mixed effect analysis of variance. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normal-theory CIs, this approach was equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 1.727 | |
| Confidence Interval |
(2-Sided) 90% 0.977 to 3.052 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Due to the nature of the normal-theory CIs, this approach is equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Severe Hepatic Impairment, Normal Hepatic Function Matched to Severe Hepatic Function. |
|---|---|---|
| Comments | The primary comparison was each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the primary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the log-transformed data was calculated using a mixed effect analysis of variance | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normal-theory CIs, this approach was equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometic Mean Ratio |
| Estimated Value | 1.041 | |
| Confidence Interval |
(2-Sided) 90% 0.506 to 2.142 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Due to the nature of the normal-theory CIs, this approach is equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance. | |
| Title | Unbound Maximum Plasma Concentration of Brexpiprazole (Cmax,u) |
|---|---|
| Description | Blood samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose/ET. Cmax,u is the highest measured unbound plasma concentration during the dosing interval. |
| Time Frame | Day 1 to Day 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations. |
| Arm/Group Title | Mild Hepatic Impairment | Normal Hepatic Function Matched to Mild Hepatic Function. | Moderate Hepatic Impairment | Normal Hepatic Function Matched to Moderate Hepatic Function. | Severe Hepatic Impairment | Normal Hepatic Function Matched to Severe Hepatic Function. |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. | Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. | Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled |
| Measure Participants | 8 | 8 | 8 | 8 | 6 | 6 |
| Mean (Standard Deviation) [ng/mL] |
0.104
(0.0259)
|
0.114
(0.0270)
|
0.0648
(0.0143)
|
0.0779
(0.0224)
|
0.0392
(0.0105)
|
0.0760
(0.0258)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Mild Hepatic Impairment, Normal Hepatic Function Matched to Mild Hepatic Function |
|---|---|---|
| Comments | The primary comparison was each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the primary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the log-transformed data was calculated using a mixed effect analysis of variance | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normal-theory CIs, this approach was equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 0.904 | |
| Confidence Interval |
(2-Sided) 90% 0.707 to 1.156 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Due to the nature of the normal-theory CIs, this approach is equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Moderate Hepatic Impairment, Normal Hepatic Function Matched to Moderate Hepatic Function. |
|---|---|---|
| Comments | The primary comparison was each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the primary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the log-transformed data was calculated using a mixed effect analysis of variance | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normal-theory CIs, this approach was equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 0.850 | |
| Confidence Interval |
(2-Sided) 90% 0.665 to 1.087 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Due to the nature of the normal-theory CIs, this approach is equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Severe Hepatic Impairment, Normal Hepatic Function Matched to Severe Hepatic Function. |
|---|---|---|
| Comments | The primary comparison was each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the primary PK parameters between each hepatic disease group and the control group, the 90% confidence interval (CI) for the difference in the means of the log-transformed data was calculated using a mixed effect analysis of variance | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normal-theory CIs, this approach was equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 0.531 | |
| Confidence Interval |
() 90% 0.399 to 0.705 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Due to the nature of the normal-theory CIs, this approach is equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance. | |
| Title | Area Under the Curve of Brexpiprazole Calculated to the Last Observable Concentration at Time t (AUCt) |
|---|---|
| Description | Blood samples were taken at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose/ET. AUCt= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t) The AUCt was estimated using the linear trapezoidal rule. |
| Time Frame | Day 1 to Day 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations. |
| Arm/Group Title | Mild Hepatic Impairment | Normal Hepatic Function Matched to Mild Hepatic Function. | Moderate Hepatic Impairment | Normal Hepatic Function Matched to Moderate Hepatic Function. | Severe Hepatic Impairment | Normal Hepatic Function Matched to Severe Hepatic Function. |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each participant with normal hepatic function was matched to a participant with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. | Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each participant with normal hepatic function was matched to a participant with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. | Participants with normal hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each participant with normal hepatic function was matched to a particpant with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. |
| Measure Participants | 8 | 8 | 8 | 8 | 6 | 6 |
| Mean (Standard Deviation) [ng*h/mL] |
1271
(569)
|
1145
(539)
|
1213
(405)
|
1048
(422)
|
622
(163)
|
817
(306)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Mild Hepatic Impairment, Normal Hepatic Function Matched to Mild Hepatic Function |
|---|---|---|
| Comments | The secondary comparisons were each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the secondary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the log-transformed data was calculated using a mixed effect analysis of variance. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normal-theory CIs, this approach was equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 1.103 | |
| Confidence Interval |
(2-Sided) 90% 0.774 to 1.573 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Due to the nature of the normal-theory CIs, this approach is equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Moderate Hepatic Impairment, Normal Hepatic Function Matched to Moderate Hepatic Function. |
|---|---|---|
| Comments | The secondary comparisons were each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the secondary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the log-transformed data was calculated using a mixed effect analysis of variance. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normal-theory CIs, this approach was equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 1.199 | |
| Confidence Interval |
(2-Sided) 90% 0.841 to 1.710 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Due to the nature of the normal-theory CIs, this approach is equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Severe Hepatic Impairment, Normal Hepatic Function Matched to Severe Hepatic Function. |
|---|---|---|
| Comments | The secondary comparisons were each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the secondary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the log-transformed data was calculated using a mixed effect analysis of variance. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normal-theory CIs, this approach was equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 0.790 | |
| Confidence Interval |
(2-Sided) 90% 0.524 to 1.189 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Due to the nature of the normal-theory CIs, this approach is equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance. | |
| Title | Area Under the Concentration Time Curve of Brexpiprazole From Time Zero to Infinity (AUC∞) |
|---|---|
| Description | Blood samples were taken at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose/ET. AUC (0 - ∞)= AUC from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞). The AUC∞ was estimated using the linear trapezoidal rule |
| Time Frame | Day 1 to Day 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations. |
| Arm/Group Title | Mild Hepatic Impairment | Normal Hepatic Function Matched to Mild Hepatic Function. | Moderate Hepatic Impairment | Normal Hepatic Function Matched to Moderate Hepatic Function. | Severe Hepatic Impairment | Normal Hepatic Function Matched to Severe Hepatic Function. |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each participant with normal hepatic function was matched to a participant with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participant with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. | Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each participant with normal hepatic function was matched to a participant with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. | Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each participant with normal hepatic function was matched to a participant ith hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. |
| Measure Participants | 7 | 6 | 7 | 7 | 3 | 5 |
| Mean (Standard Deviation) [ng*h/mL] |
1827
(1103)
|
1393
(881)
|
1960
(579)
|
1345
(697)
|
831
(234)
|
788
(230)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Mild Hepatic Impairment, Normal Hepatic Function Matched to Mild Hepatic Function |
|---|---|---|
| Comments | The secondary comparisons were each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the secondary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the log-transformed data was calculated using a mixed effect analysis of variance. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normal-theory CIs, this approach was equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 1.241 | |
| Confidence Interval |
(2-Sided) 90% 0.719 to 2.143 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Due to the nature of the normal-theory CIs, this approach is equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Moderate Hepatic Impairment, Normal Hepatic Function Matched to Moderate Hepatic Function. |
|---|---|---|
| Comments | The secondary comparisons were each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the secondary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the log-transformed data was calculated using a mixed effect analysis of variance. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normal-theory CIs, this approach was equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 1.604 | |
| Confidence Interval |
(2-Sided) 90% 0.942 to 2.732 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Due to the nature of the normal-theory CIs, this approach is equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Severe Hepatic Impairment, Normal Hepatic Function Matched to Severe Hepatic Function. |
|---|---|---|
| Comments | The secondary comparisons were each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the secondary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the log-transformed data was calculated using a mixed effect analysis of variance. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normal-theory CIs, this approach was equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 1.077 | |
| Confidence Interval |
(2-Sided) 90% 0.540 to 2.146 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Due to the nature of the normal-theory CIs, this approach is equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance. | |
| Title | Maximum Plasma Concentration of Brexpiprazole (Cmax) |
|---|---|
| Description | Blood samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose/ET. Cmax is the highest measured concentration of the drug during the dosing interval. Actual blood sample times were used for PK calculations. Values for Cmax and tmax were determined directly from the observed data. |
| Time Frame | Day 1 to Day 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations. |
| Arm/Group Title | Mild Hepatic Impairment | Normal Hepatic Function Matched to Mild Hepatic Function. | Moderate Hepatic Impairment | Normal Hepatic Function Matched to Moderate Hepatic Function. | Severe Hepatic Impairment | Normal Hepatic Function Matched to Severe Hepatic Function. |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each participant with normal hepatic function was matched to a participant with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. | Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each participant with normal hepatic function was matched to a participant with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. | Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. |
| Measure Participants | 8 | 8 | 8 | 8 | 6 | 6 |
| Mean (Standard Deviation) [ng/mL] |
22.9
(7.60)
|
26.7
(9.09)
|
14.6
(4.63)
|
19.3
(4.98)
|
7.65
(2.69)
|
17.7
(7.38)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Mild Hepatic Impairment, Normal Hepatic Function Matched to Mild Hepatic Function |
|---|---|---|
| Comments | The secondary comparisons were each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the secondary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the log-transformed data was calculated using a mixed effect analysis of variance. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normal-theory CIs, this approach was equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric mean ratio |
| Estimated Value | 0.856 | |
| Confidence Interval |
(2-Sided) 90% 0.691 to 1.059 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Due to the nature of the normal-theory CIs, this approach is equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Moderate Hepatic Impairment, Normal Hepatic Function Matched to Moderate Hepatic Function. |
|---|---|---|
| Comments | The secondary comparisons were each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the secondary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the log-transformed data was calculated using a mixed effect analysis of variance. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normal-theory CIs, this approach was equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 0.742 | |
| Confidence Interval |
(2-Sided) 90% 0.599 to 0.918 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Due to the nature of the normal-theory CIs, this approach is equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Severe Hepatic Impairment, Normal Hepatic Function Matched to Severe Hepatic Function. |
|---|---|---|
| Comments | The secondary comparisons were each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the secondary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the log-transformed data was calculated using a mixed effect analysis of variance. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normal-theory CIs, this approach was equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 0.451 | |
| Confidence Interval |
(2-Sided) 90% 0.352 to 0.577 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Due to the nature of the normal-theory CIs, this approach is equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance. | |
| Title | Time to Cmax of Brexiprazole (Tmax) |
|---|---|
| Description | Blood samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose/ET. Tmax is the time taken to reach highest measured concentration of the drug during the dosing interval. Actual blood sample times were used for PK calculations. Values for Cmax and tmax were determined directly from the observed data. |
| Time Frame | Day 1 to Day 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations. |
| Arm/Group Title | Mild Hepatic Impairment | Normal Hepatic Function Matched to Mild Hepatic Function. | Moderate Hepatic Impairment | Normal Hepatic Function Matched to Moderate Hepatic Function. | Severe Hepatic Function | Normal Hepatic Function Matched to Severe Hepatic Function. |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each participant with normal hepatic function was matched to a participant with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. | Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each participant with normal hepatic function was matched to a participant with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. | Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each participant with normal hepatic function was matched to a participant with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. |
| Measure Participants | 8 | 8 | 8 | 8 | 6 | 6 |
| Median (Full Range) [h] |
3.50
|
3.50
|
4.50
|
4.50
|
5.00
|
5.00
|
| Title | Apparent Clearance of Brexpiprazole From Plasma After Extravascular Administration (CL/F) |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations. |
| Arm/Group Title | Mild Hepatic Impairment | Normal Hepatic Function Matched to Mild Hepatic Function. | Moderate Hepatic Impairment | Normal Hepatic Function Matched to Moderate Hepatic Function. | Severe Hepatic Impairment | Normal Hepatic Function Matched to Severe Hepatic Function. |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each participant with normal hepatic function was matched to a participants with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Partipants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. | Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each participant with normal hepatic function was matched to a participant with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. | Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each participant with normal hepatic function was matched to a participant with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. |
| Measure Participants | 7 | 6 | 7 | 6 | 3 | 5 |
| Mean (Standard Deviation) [mL/h/kg] |
24.5
(28.2)
|
25.4
(12.3)
|
13.8
(2.72)
|
26.0
(19.2)
|
28.2
(6.70)
|
34.2
(16.3)
|
| Title | Unbound Fraction of Brexpiprazole in Plasma (fu) |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations. |
| Arm/Group Title | Mild Hepatic Function | Normal Hepatic Function Matched to Mild Hepatic Function. | Moderate Hepatic Function | Normal Hepatic Function Matched to Moderate Hepatic Function. | Severe Hepatic Function | Normal Hepatic Function Matched to Severe Hepatic Function. |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each participant with normal hepatic function was matched to a participant with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. | Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each participant with normal hepatic function was matched to a participant with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. | Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each participant with normal hepatic function was matched to a participant with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Participants with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. |
| Measure Participants | 8 | 8 | 8 | 8 | 6 | 6 |
| Mean (Standard Deviation) [% unbound drug in the urine] |
0.472
(0.0840)
|
0.451
(0.112)
|
0.462
(0.0786)
|
0.400
(0.0442)
|
0.544
(0.186)
|
0.450
(0.0795)
|
| Title | Apparent Unbound Clearance of Brexpiprazole From Plasma After Extravascular Administration (CLu/F) |
|---|---|
| Description | Blood samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose/ET. The value of CLu/F (brexpiprazole only) was determined as dose normalized unbound area under the concentration-time curve from time zero to infinity (Dose/AUC∞,u). |
| Time Frame | Day 1 to Day 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations. |
| Arm/Group Title | Mild Hepatic Impairment | Normal Hepatic Function Matched to Mild Hepatic Function. | Moderate Hepatic Function | Normal Hepatic Function Matched to Moderate Hepatic Function. | Severe Hepatic Function | Normal Hepatic Function Matched to Severe Hepatic Function. |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. | Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled | Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled |
| Measure Participants | 7 | 6 | 7 | 7 | 3 | 5 |
| Mean (Standard Deviation) [mL/h/kg] |
5674
(7165)
|
5730
(2944)
|
3115
(494)
|
6768
(5833)
|
6598
(1182)
|
7697
(2653)
|
| Title | Terminal-phase Elimination Half-life of Brexpiprazole (t1/2,z) |
|---|---|
| Description | Blood samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose/ET. The t1/2,z was determined as (ln2)/λz. Terminal-phase elimination half-life is the time measured for the plasma concentration to decrease by one half. |
| Time Frame | Day 1 to Day 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations. |
| Arm/Group Title | Mild Hepatic Function | Normal Hepatic Function Matched to Mild Hepatic Function. | Moderate Hepatic Function | Normal Hepatic Function Matched to Moderate Hepatic Function. | Sever Hepatic Function | Normal Hepatic Function Matched to Severe Hepatic Function. |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. | Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. | Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled |
| Measure Participants | 7 | 6 | 7 | 7 | 3 | 5 |
| Mean (Standard Deviation) [h] |
103
(51.1)
|
64.7
(24.6)
|
116
(25.8)
|
64.2
(26.2)
|
81.1
(17.1)
|
51.4
(8.21)
|
| Title | Renal Clearance (CLr) of Brexipiprazole |
|---|---|
| Description | Urine samples were taken at pre-dose and during the following increments: 0 to 24, 24 to 48, 48 to 72, 72 to 96, 96 to 120, 120 to 144, and 144 to 168 hours postdose. The value of CLr was calculated as Ae,u/AUCt. |
| Time Frame | Day 1 to Day 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations. |
| Arm/Group Title | Mild Hepatic Impairment | Normal Hepatic Function Matched to Mild Hepatic Function. | Moderate Hepatic Impairment | Normal Hepatic Function Matched to Moderate Hepatic Function. | Severe Hepatic Impairment | Normal Hepatic Function Matched to Severe Hepatic Function. |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. | Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. | Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. |
| Measure Participants | 8 | 8 | 8 | 8 | 6 | 6 |
| Mean (Standard Deviation) [mL/h/kg] |
0.0468
(0.0353)
|
0.0263
(0.0244)
|
0.0360
(0.0286)
|
0.0422
(0.0383)
|
0.0402
(0.0872)
|
0.0193
(0.0203)
|
| Title | Cumulative Amount of Brexpiprazole Excreted Into the Urine (Ae,u) |
|---|---|
| Description | Urine samples were taken at pre-dose and during the following increments: 0 to 24, 24 to 48, 48 to 72, 72 to 96, 96 to 120, 120 to 144, and 144 to 168 hours postdose. The value of Ae,u was calculated as the summation of urine concentration × urine volume from each collection interval |
| Time Frame | Day 1 to Day 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations. |
| Arm/Group Title | Mild Hepatic Function | Normal Hepatic Function Matched to Mild Hepatic Function. | Moderate Hepatic Function | Normal Hepatic Function Matched to Moderate Hepatic Function. | Severe Hepatic Function | Normal Hepatic Function Matched to Severe Hepatic Function. |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. | Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. | Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. |
| Measure Participants | 8 | 8 | 8 | 8 | 6 | 6 |
| Mean (Standard Deviation) [ng] |
4511
(3808)
|
1854
(1500)
|
3522
(2740)
|
3837
(3358)
|
2090
(4699)
|
1326
(1427)
|
| Title | Fraction of Systemically Available Brexpiprazole Excreted Into the Urine (fe,u) |
|---|---|
| Description | Urine samples were taken at pre-dose and during the following increments: 0 to 24, 24 to 48, 48 to 72, 72 to 96, 96 to 120, 120 to 144, and 144 to 168 hours postdose.. The value of fe,u was calculated as 100 × Ae,u/Dose. |
| Time Frame | Day 1 to Day 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations. |
| Arm/Group Title | Mild Hepatic Impairment | Normal Hepatic Function Matched to Mild Hepatic Function. | Moderate Hepatic Impairment | Normal Hepatic Function Matched to Moderate Hepatic Function | Severe Hepatic Impairment | Normal Hepatic Function Matched to Severe Hepatic Function. |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. | Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. | Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. |
| Measure Participants | 8 | 8 | 8 | 8 | 6 | 6 |
| Mean (Standard Deviation) [% of drug in urine] |
0.226
(0.190)
|
0.0927
(0.0750)
|
0.176
(0.137)
|
0.192
(0.168)
|
0.104
(0.235)
|
0.0663
(0.0713)
|
| Title | AUCt for DM-3411 Metabolite |
|---|---|
| Description | Blood samples were taken at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose/ET. AUCt= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t) The AUCt was estimated using the linear trapezoidal rule. |
| Time Frame | Day 1 to Day 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations. |
| Arm/Group Title | Mild Hepatic Impairment | Normal Hepatic Function Matched to Mild Hepatic Function. | Moderate Hepatic Impairment | Normal Hepatic Function Matched to Moderate Hepatic Function. | Severe Hepatic Impairment | Normal Hepatic Function Matched to Severe Hepatic Function. |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. | Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. | Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. |
| Measure Participants | 8 | 8 | 8 | 8 | 6 | 6 |
| Mean (Standard Deviation) [ng*h/mL] |
380
(195)
|
683
(246)
|
284
(164)
|
486
(263)
|
151
(51.4)
|
479
(226)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Mild Hepatic Impairment, Normal Hepatic Function Matched to Mild Hepatic Function |
|---|---|---|
| Comments | The secondary comparisons were each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the secondary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the log-transformed data was calculated using a mixed effect analysis of variance. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normal-theory CIs, this approach was equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 0.509 | |
| Confidence Interval |
(2-Sided) 90% 0.346 to 0.748 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Moderate Hepatic Impairment, Normal Hepatic Function Matched to Moderate Hepatic Function. |
|---|---|---|
| Comments | The secondary comparisons were each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the secondary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the log-transformed data was calculated using a mixed effect analysis of variance. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normal-theory CIs, this approach was equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 0.586 | |
| Confidence Interval |
(2-Sided) 90% 0.399 to 0.861 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Due to the nature of the normal-theory CIs, this approach is equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Severe Hepatic Impairment, Normal Hepatic Function Matched to Severe Hepatic Function. |
|---|---|---|
| Comments | The secondary comparisons were each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the secondary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the log-transformed data was calculated using a mixed effect analysis of variance. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normal-theory CIs, this approach was equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 0.334 | |
| Confidence Interval |
(2-Sided) 90% 0.214 to 0.521 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Due to the nature of the normal-theory CIs, this approach is equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance. | |
| Title | AUC∞ for DM-3411 Metabolite |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations. |
| Arm/Group Title | Mild Hepatic Impairment | Normal Hepatic Function Matched to Mild Hepatic Function. | Moderate Hepatic Impairment | Normal Hepatic Function Matched to Moderate Hepatic Function. | Severe Hepatic Impairment | Normal Hepatic Function Matched to Severe Hepatic Function. |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. | Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. | Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. |
| Measure Participants | 5 | 6 | 6 | 6 | 4 | 3 |
| Mean (Standard Deviation) [ng*h/mL] |
489
(210)
|
692
(259)
|
382
(262)
|
530
(211)
|
187
(67.2)
|
329
(167)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Mild Hepatic Impairment, Normal Hepatic Function Matched to Mild Hepatic Function |
|---|---|---|
| Comments | The secondary comparisons were each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the secondary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the log-transformed data was calculated using a mixed effect analysis of variance. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normal-theory CIs, this approach was equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 0.716 | |
| Confidence Interval |
(2-Sided) 90% 0.445 to 1.153 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Moderate Hepatic Impairment, Normal Hepatic Function Matched to Moderate Hepatic Function. |
|---|---|---|
| Comments | The secondary comparisons were each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the secondary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the log-transformed data was calculated using a mixed effect analysis of variance. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normal-theory CIs, this approach was equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 0.594 | |
| Confidence Interval |
(2-Sided) 90% 0.378 to 0.934 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Severe Hepatic Impairment, Normal Hepatic Function Matched to Severe Hepatic Function. |
|---|---|---|
| Comments | The secondary comparisons were each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the secondary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the log-transformed data was calculated using a mixed effect analysis of variance. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normal-theory CIs, this approach was equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 0.561 | |
| Confidence Interval |
(2-Sided) 90% 0.308 to 1.022 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Cmax for DM-3411 Metabolite |
|---|---|
| Description | Blood samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose/ET. Cmax is the highest measured concentration of the metabolite during the dosing interval. |
| Time Frame | Day 1 to Day 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations. |
| Arm/Group Title | Mild Hepatic Impairment | Normal Hepatic Function Matched to Mild Hepatic Function. | Moderate Hepatic Impairment | Normal Hepatic Function Matched to Moderate Hepatic Function. | Severe Hepatic Impairment | Normal Hepatic Function Matched to Severe Hepatic Function. |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. | Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled | Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. |
| Measure Participants | 8 | 8 | 8 | 8 | 6 | 6 |
| Mean (Standard Deviation) [ng/mL] |
6.49
(5.13)
|
10.5
(4.26)
|
3.19
(1.56)
|
7.25
(4.83)
|
2.15
(0.880)
|
7.13
(3.73)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Mild Hepatic Impairment, Normal Hepatic Function Matched to Mild Hepatic Function |
|---|---|---|
| Comments | The secondary comparisons were each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the secondary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the log-transformed data was calculated using a mixed effect analysis of variance. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normal-theory CIs, this approach was equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 0.558 | |
| Confidence Interval |
(2-Sided) 90% 0.368 to 0.845 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Moderate Hepatic Impairment, Normal Hepatic Function Matched to Moderate Hepatic Function. |
|---|---|---|
| Comments | The secondary comparisons were each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the secondary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the log-transformed data was calculated using a mixed effect analysis of variance. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normal-theory CIs, this approach was equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 0.516 | |
| Confidence Interval |
(2-Sided) 90% 0.341 to 0.781 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Severe Hepatic Impairment, Normal Hepatic Function Matched to Severe Hepatic Function. |
|---|---|---|
| Comments | The secondary comparisons were each hepatic disease group (mild, moderate or severe) versus the control (normal group). To compare the secondary PK parameters between each hepatic disease group and the control group, the 90% CI for the difference in the means of the log-transformed data was calculated using a mixed effect analysis of variance. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | Bioequivalence was claimed for a PK parameter if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0]. Due to the nature of the normal-theory CIs, this approach was equivalent to carrying out two 1-sided tests of hypothesis at the 5% level of significance. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Mean Ratio |
| Estimated Value | 0.314 | |
| Confidence Interval |
(2-Sided) 90% 0.195 to 0.507 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Tmax for DM-3411 Metabolite |
|---|---|
| Description | Blood samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose/ET. Tmax is the time taken to reach highest measured concentration of the metabolite during the dosing interval. |
| Time Frame | Day 1 to Day 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations. |
| Arm/Group Title | Mild Hepatic Function | Normal Hepatic Function Matched to Mild Hepatic Function. | Moderate Hepatic Function | Normal Hepatic Function Matched to Moderate Hepatic Function. | Severe Hepatic Function | Normal Hepatic Function Matched to Severe Hepatic Function. |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. | Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. | Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. |
| Measure Participants | 8 | 8 | 8 | 8 | 6 | 6 |
| Median (Full Range) [h] |
5.00
|
6.00
|
5.00
|
7.00
|
4.5
|
6.00
|
| Title | t1/2,z for DM-3411 Metabolite |
|---|---|
| Description | Blood samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose/ET. The t1/2,z was determined as (ln2)/λz. |
| Time Frame | Day 1 to Day 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations. |
| Arm/Group Title | Mild Hepatic Impairment | Normal Hepatic Function Matched to Mild Hepatic Function. | Moderate Hepatic Impairment | Normal Hepatic Function Matched to Moderate Hepatic Function. | Severe Hepatic Impairment | Normal Hepatic Function Matched to Severe Hepatic Function. |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. | Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. | Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. |
| Measure Participants | 5 | 6 | 6 | 6 | 4 | 3 |
| Mean (Standard Deviation) [h] |
78.8
(37.6)
|
59.7
(15.7)
|
87.2
(45.7)
|
62.0
(26.4)
|
84.6
(12.0)
|
56.1
(8.25)
|
| Title | Ae,u for DM-3411 Metabolite |
|---|---|
| Description | Urine samples were taken at pre-dose and during the following increments: 0 to 24, 24 to 48, 48 to 72, 72 to 96, 96 to 120, 120 to 144, and 144 to 168 hours postdose. The value of Ae,u was calculated as the summation of urine concentration × urine volume from each collection interval. |
| Time Frame | Day 1 to Day 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations. |
| Arm/Group Title | Mild Hepatic Function | Normal Hepatic Function Matched to Mild Hepatic Function. | Moderate Hepatic Function | Normal Hepatic Function Matched to Moderate Hepatic Function. | Severe Hepatic Function | Normal Hepatic Function Matched to Severe Hepatic Function. |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. | Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled | Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. |
| Measure Participants | 8 | 8 | 8 | 8 | 6 | 6 |
| Mean (Standard Deviation) [ng] |
67086
(25276)
|
81148
(23188)
|
68413
(16993)
|
71353
(41630)
|
48190
(14756)
|
83604
(34907)
|
| Title | fe,u for DM-3411 Metabolite |
|---|---|
| Description | Urine samples were taken at pre-dose and during the following increments: 0 to 24, 24 to 48, 48 to 72, 72 to 96, 96 to 120, 120 to 144, and 144 to 168 hours postdose. The value of fe,u was calculated as 100 × Ae,u/Dose. |
| Time Frame | Day 1 to Day 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations. |
| Arm/Group Title | Mild Hepatic Function | Normal Hepatic Function Matched to Mild Hepatic Function. | Moderate Hepatic Function | Normal Hepatic Function Matched to Moderate Hepatic Function. | Severe Hepatic Function | Normal Hepatic Function Matched to Severe Hepatic Function. |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. | Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg | Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. | Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. |
| Measure Participants | 8 | 8 | 8 | 8 | 6 | 6 |
| Mean (Standard Deviation) [% metabolite excreted in urine] |
3.23
(1.22)
|
3.91
(1.12)
|
3.30
(0.819)
|
3.44
(2.01)
|
2.32
(0.712)
|
4.03
(1.68)
|
| Title | CLr for DM-3411 Metabolite |
|---|---|
| Description | Urine samples were taken at pre-dose and during the following increments: 0 to 24, 24 to 48, 48 to 72, 72 to 96, 96 to 120, 120 to 144, and 144 to 168 hours postdose. The value of CLr was calculated as Ae,u/AUCt. |
| Time Frame | Day 1 to Day 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK set consisting of all evaluable brexpiprazole PK parameters from enrolled particpants who had evaluable plasma concentrations. |
| Arm/Group Title | Mild Hepatic Impairment | Normal Hepatic Function Matched to Mild Hepatic Function. | Moderate Hepatic Impairment | Normal Hepatic Function Matched to Moderate Hepatic Function. | Severe Hepatic Impairment | Normal Hepatic Function Matched to Severe Hepatic Function. |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. | Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. | Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function received a single oral dose of brexpiprazole 2 mg. Each subject with normal hepatic function was matched to a subject with hepatic impairment by age (within the decile or ± 5 years, whichever was less), sex, and weight (± 15%). Subjects with hepatic impairment and within 30% of their ideal body weight (minimum body weight of 50 kg) were enrolled. |
| Measure Participants | 8 | 8 | 8 | 8 | 6 | 6 |
| Mean (Standard Deviation) [mL/h/kg] |
2.67
(1.31)
|
1.83
(0.828)
|
3.96
(2.32)
|
1.90
(0.568)
|
4.08
(1.68)
|
2.33
(1.01)
|
| Title | Number of Adverse Events (AEs) Reported |
|---|---|
| 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants who received at least one dose of study drug were included in the safety analysis. |
| Arm/Group Title | Mild Hepatic Impairment | Moderate Hepatic Impairment | Severe Hepatic Impairment | Normal Hepatic Function |
|---|---|---|---|---|
| Arm/Group Description | Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. |
| Measure Participants | 8 | 8 | 6 | 23 |
| Adverse events |
3
|
5
|
1
|
8
|
| Treatment emergent adverse events |
3
|
5
|
1
|
6
|
| Serious adverse events |
0
|
0
|
0
|
0
|
| Title | Number of Participants With Changes From Baseline in Vital Signs Parameters. |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The abnormal values of vital signs values in participants are captured as serious AEs/AEs and are reported in the SAE or other AE section of this results report. |
| Arm/Group Title | Mild Hepatic Impairment | Moderate Hepatic Impairment | Severe Hepatic Impairment | Normal Hepatic Function |
|---|---|---|---|---|
| Arm/Group Description | Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. |
| Measure Participants | 8 | 8 | 6 | 23 |
| Number [Participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Number of Participants With Changes From Baseline in Electrocardiogram (ECG) Parameters. |
|---|---|
| Description | Electrocardiograms were performed at Screening, Day -1, and Day 1 at predose (in triplicate; within 45 minutes prior to dosing), and 2, 4, 6, 8, 12, 24, 72, 120, and 168/ET hours postdose. Standard 12-lead ECGs were performed after the subject was supine and at rest for ≥ 10 minutes prior to the ECG. |
| Time Frame | Day-1 to Day 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The abnormal values of ECG values in participants are captured as serious AEs/AEs and are reported in the SAE or other AE section of this results report. |
| Arm/Group Title | Mild Hepatic Impairment | Moderate Hepatic Impairment | Severe Hepatic Impairment | Normal Hepatic Function |
|---|---|---|---|---|
| Arm/Group Description | Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. |
| Measure Participants | 8 | 8 | 6 | 23 |
| Number [Participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Number of Participants With Changes From Baseline in Serum Chemistry, Hematology and Urinalysis Parameters. |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The abnormal values of laboratory values in participants are captured as serious AEs/AEs and are reported in the SAE or other AE section of this results report. |
| Arm/Group Title | Mild Hepatic Impairment | Moderate Hepatic Impairment | Severe Hepatic Impairment | Normal Hepatic Function |
|---|---|---|---|---|
| Arm/Group Description | Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. |
| Measure Participants | 8 | 8 | 6 | 23 |
| Number [Participant] |
0
|
0
|
0
|
0
|
| Title | Incidence of Suicidality, Suicidal Behaviour or Suicidal Ideation as Measured by the Columbia-Suicide Severity Rating Scale (C-SSRS) |
|---|---|
| Description | The Baseline version of the C-SSRS was administered at Screening. The Since Last Visit version of the C-SSRS was administered on Day 1 at predose and on Days 4 and 7. |
| Time Frame | Day 1, Day 4, Day 7 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Suicidality, suicidal behaviour or suicidal ideation are captured as serious AEs/AEs and are reported in the SAE or other AE section of this results report. |
| Arm/Group Title | Mild Hepatic Impairment | Moderate Hepatic Impairment | Severe Hepatic Impairment | Normal Hepatic Function |
|---|---|---|---|---|
| Arm/Group Description | Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. |
| Measure Participants | 8 | 8 | 6 | 23 |
| Number [Participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
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. | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. | |||||||
| Arm/Group Title | Mild Hepatic Impairment | Moderate Hepatic Impairment | Severe Hepatic Impairment | Normal Hepatic Function | ||||
| Arm/Group Description | Participants with mild hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with moderate hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with severe hepatic impairment (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | Participants with normal hepatic function (Child-Pugh classification scheme) received a single oral dose of brexpiprazole 2 mg. | ||||
All Cause Mortality |
||||||||
| Mild Hepatic Impairment | Moderate Hepatic Impairment | Severe Hepatic Impairment | Normal Hepatic Function | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||
Serious Adverse Events |
||||||||
| Mild Hepatic Impairment | Moderate Hepatic Impairment | Severe Hepatic Impairment | Normal Hepatic Function | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 0/23 (0%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| Mild Hepatic Impairment | Moderate Hepatic Impairment | Severe Hepatic Impairment | Normal Hepatic Function | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/8 (37.5%) | 3/8 (37.5%) | 1/6 (16.7%) | 6/23 (26.1%) | ||||
| Gastrointestinal disorders | ||||||||
| Diarrhoea | 0/8 (0%) | 1/8 (12.5%) | 0/6 (0%) | 0/23 (0%) | ||||
| General disorders | ||||||||
| Fatigue | 1/8 (12.5%) | 1/8 (12.5%) | 0/6 (0%) | 0/23 (0%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Musculoskeletal pain | 0/8 (0%) | 0/8 (0%) | 0/6 (0%) | 1/23 (4.3%) | ||||
| Nervous system disorders | ||||||||
| Dizziness | 1/8 (12.5%) | 0/8 (0%) | 0/6 (0%) | 0/23 (0%) | ||||
| Headache | 1/8 (12.5%) | 1/8 (12.5%) | 1/6 (16.7%) | 4/23 (17.4%) | ||||
| Somnolence | 0/8 (0%) | 1/8 (12.5%) | 0/6 (0%) | 1/23 (4.3%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Cough | 0/8 (0%) | 1/8 (12.5%) | 0/6 (0%) | 0/23 (0%) | ||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Global Medical Affairs |
|---|---|
| Organization | Otsuka Pharmaceutical Development and Commercialization, Inc. |
| Phone | 800-562-3974 |
Responsible Party:
Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier:
NCT01299454
Other Study ID Numbers:
- 331-09-225
First Posted:
Feb 18, 2011
Last Update Posted:
Oct 20, 2015
Last Verified:
Sep 1, 2015