SchizophreniaPhase 1NCT01299454

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

A Phase 1 study testing OPC-34712 in people with Schizophrenia, run by Otsuka Pharmaceutical Development & Commercialization, Inc. at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 years and olderHealthy volunteers can take part
Conditions the study is for: Schizophrenia
What is being tested?: OPC-34712
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 45 participants
Where: 3 sitesUnited States
Study dates: Dec 2010to Jul 2011
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

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.
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.

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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.

Who cannot join

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.

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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.
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).

Trial locations and contacts

3 sites in 1 country.

United States3 sites

Study Site
Miami, Florida, 33014
Study Site
Minneapolis, Minnesota, 55404
Study Site
San Antonio, Texas, 78212

Other trials in United States

About this study

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

Read the 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.

Conditions: Schizophrenia
Being tested: OPC-34712
Medical subject headings: Schizophrenia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

OPC-34712Drug
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.

Study groups in NCT01299454
Study group	Role	What they receive
Normal	Active comparator	Not described Receives: Drug: OPC-34712
Mild	Active comparator	Not described Receives: Drug: OPC-34712
Moderate	Active comparator	Not described Receives: Drug: OPC-34712
Severe	Active comparator	Not described Receives: Drug: OPC-34712

What is being measured

The primary outcome is the main question the study is designed to answer.

Unbound Brexpiprazole Area Under the Concentration Time Curve (AUC) Calculated to the Last Observable Concentration at Time t (AUCt,u)
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).
Measured: Day 1 to Day 8
Unbound Brexpiprazole AUC Calculated From Time Zero to Infinity (AUC∞,u)
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 - ∞).
Measured: Day 1 to Day 8
Unbound Maximum Plasma Concentration of Brexpiprazole (Cmax,u)
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.
Measured: Day 1 to Day 8

Secondary outcomes (24)

Area Under the Curve of Brexpiprazole Calculated to the Last Observable Concentration at Time t (AUCt)
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.
Measured: Day 1 to Day 8
Area Under the Concentration Time Curve of Brexpiprazole From Time Zero to Infinity (AUC∞)
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
Measured: Day 1 to Day 8
Maximum Plasma Concentration of Brexpiprazole (Cmax)
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.
Measured: Day 1 to Day 8
Time to Cmax of Brexiprazole (Tmax)
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.
Measured: Day 1 to Day 8
Apparent Clearance of Brexpiprazole From Plasma After Extravascular Administration (CL/F)
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.
Measured: Day 1 to Day 8
Unbound Fraction of Brexpiprazole in Plasma (fu)
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.
Measured: Day 1 to Day 8
Apparent Unbound Clearance of Brexpiprazole From Plasma After Extravascular Administration (CLu/F)
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).
Measured: Day 1 to Day 8
Terminal-phase Elimination Half-life of Brexpiprazole (t1/2,z)
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.
Measured: Day 1 to Day 8
Renal Clearance (CLr) of Brexipiprazole
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.
Measured: Day 1 to Day 8
Cumulative Amount of Brexpiprazole Excreted Into the Urine (Ae,u)
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
Measured: Day 1 to Day 8
Fraction of Systemically Available Brexpiprazole Excreted Into the Urine (fe,u)
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.
Measured: Day 1 to Day 8
AUCt for DM-3411 Metabolite
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.
Measured: Day 1 to Day 8
AUC∞ for DM-3411 Metabolite
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.
Measured: Day 1 to Day 8
Cmax for DM-3411 Metabolite
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.
Measured: Day 1 to Day 8
Tmax for DM-3411 Metabolite
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.
Measured: Day 1 to Day 8
t1/2,z for DM-3411 Metabolite
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.
Measured: Day 1 to Day 8
Ae,u for DM-3411 Metabolite
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.
Measured: Day 1 to Day 8
fe,u for DM-3411 Metabolite
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.
Measured: Day 1 to Day 8
CLr for DM-3411 Metabolite
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.
Measured: Day 1 to Day 8
Number of Adverse Events (AEs) Reported
AEs were captured for all participants from the time the ICF was signed until the end of the study
Measured: From the time the Informed Consent Form was signed, throughout the 8 day study up to 30 days after study drug administration.
Number of Participants With Changes From Baseline in Vital Signs Parameters.
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
Measured: Day -1 to Day 8
Number of Participants With Changes From Baseline in Electrocardiogram (ECG) Parameters.
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.
Measured: Day-1 to Day 8
Number of Participants With Changes From Baseline in Serum Chemistry, Hematology and Urinalysis Parameters.
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.
Measured: Day -1 to Day 8
Incidence of Suicidality, Suicidal Behaviour or Suicidal Ideation as Measured by the Columbia-Suicide Severity Rating Scale (C-SSRS)
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.
Measured: Day 1, Day 4, Day 7

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Dec 2010Jul 2011

First posted18 Feb 2011 (estimated)
Study startDec 2010
Primary completionJun 2011
Study completionJul 2011

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for SchizophreniaStudies of the same condition, open and under way.
More trials run by Otsuka Pharmaceutical Development & Commercialization, Inc.The sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 45 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01299454
Sponsor's protocol ID: 331-09-225
Status last verified: Sep 2015
First submitted: 16 Feb 2011
Last updated: 20 Oct 2015
Results posted: Yes, on ClinicalTrials.gov

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 20 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT01299454
Acronym / sponsor ID: 331-09-225
Conditions: Schizophrenia
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 45 participants (actual)
Lead sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.Industry (pharma, biotech, devices)
Study start: Dec 2010
Primary completion: Jun 2011 (actual)
Study completion: Jul 2011 (actual)
First posted: 18 Feb 2011 (estimated)
Results: Posted 3 Sep 2015

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 4

Arm	Type	Receives
Normal	Active comparator	Drug: OPC-34712
Mild	Active comparator	Drug: OPC-34712
Moderate	Active comparator	Drug: OPC-34712
Severe	Active comparator	Drug: OPC-34712

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (13 listed)

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.
Hepatically impaired subjects with creatinine clearance (CLcr) > 30 mL/min.

Key exclusion criteria (26 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
OPC-34712All 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.	Drug	Mild, Moderate, Normal, Severe

Primary outcome

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

24 secondary outcomes

Area Under the Curve of Brexpiprazole Calculated to the Last Observable Concentration at Time t (AUCt)
Time frame: Day 1 to Day 8
Area Under the Concentration Time Curve of Brexpiprazole From Time Zero to Infinity (AUC∞)
Time frame: Day 1 to Day 8
Maximum Plasma Concentration of Brexpiprazole (Cmax)
Time frame: Day 1 to Day 8
Time to Cmax of Brexiprazole (Tmax)
Time frame: Day 1 to Day 8
Apparent Clearance of Brexpiprazole From Plasma After Extravascular Administration (CL/F)
Time frame: Day 1 to Day 8
Unbound Fraction of Brexpiprazole in Plasma (fu)
Time frame: Day 1 to Day 8
Apparent Unbound Clearance of Brexpiprazole From Plasma After Extravascular Administration (CLu/F)
Time frame: Day 1 to Day 8
Terminal-phase Elimination Half-life of Brexpiprazole (t1/2,z)
Time frame: Day 1 to Day 8
Renal Clearance (CLr) of Brexipiprazole
Time frame: Day 1 to Day 8
Cumulative Amount of Brexpiprazole Excreted Into the Urine (Ae,u)
Time frame: Day 1 to Day 8
Fraction of Systemically Available Brexpiprazole Excreted Into the Urine (fe,u)
Time frame: Day 1 to Day 8
AUCt for DM-3411 Metabolite
Time frame: Day 1 to Day 8
AUC∞ for DM-3411 Metabolite
Time frame: Day 1 to Day 8
Cmax for DM-3411 Metabolite
Time frame: Day 1 to Day 8
Tmax for DM-3411 Metabolite
Time frame: Day 1 to Day 8
t1/2,z for DM-3411 Metabolite
Time frame: Day 1 to Day 8
Ae,u for DM-3411 Metabolite
Time frame: Day 1 to Day 8
fe,u for DM-3411 Metabolite
Time frame: Day 1 to Day 8
CLr for DM-3411 Metabolite
Time frame: Day 1 to Day 8
Number of Adverse Events (AEs) Reported
Time frame: From the time the Informed Consent Form was signed, throughout the 8 day study up to 30 days after study drug administration.
Number of Participants With Changes From Baseline in Vital Signs Parameters.
Time frame: Day -1 to Day 8
Number of Participants With Changes From Baseline in Electrocardiogram (ECG) Parameters.
Time frame: Day-1 to Day 8
Number of Participants With Changes From Baseline in Serum Chemistry, Hematology and Urinalysis Parameters.
Time frame: Day -1 to Day 8
Incidence of Suicidality, Suicidal Behaviour or Suicidal Ideation as Measured by the Columbia-Suicide Severity Rating Scale (C-SSRS)
Time frame: Day 1, Day 4, Day 7

Results and safety

Results posted to the registry on 3 Sep 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Mild Hepatic Impairment	8	8
Moderate Hepatic Impairment	8	8
Severe Hepatic Impairment	6	6
Normal Hepatic Function	23	23

Primary outcome: Unbound Brexpiprazole Area Under the Concentration Time Curve (AUC) Calculated to the Last Observable Concentration at Time t (AUCt,u)

Time frame: Day 1 to Day 8. Mean (Standard Deviation). Unit: nanograms.hours/mL (ng*h/mL)

Measure	Mild Hepatic Impairment n = 8	Normal Hepatic Function Matched to Mild Hepatic Function n = 8	Moderate Hepatic Impairment n = 8	Normal Hepatic Function Matched to Moderate Hepatic Function. n = 8	Severe Hepatic Impairment n = 6	Normal Hepatic Function Matched to Severe Hepatic Function. n = 6
Value	5.95 (2.58)	4.87 (1.78)	5.41 (1.37)	4.28 (1.95)	3.27 (0.93)	3.63 (1.54)

Mild Hepatic Impairment vs Normal Hepatic Function Matched to Mild Hepatic Function: Geometric Mean Ratio: 1.166 (90% CI 0.776 to 1.751), Mixed effect analysis of variance
Moderate Hepatic Impairment vs Normal Hepatic Function Matched to Moderate Hepatic Function.: Geometric Mean Ratio: 1.375 (90% CI 0.915 to 2.066), Mixed effect analysis of variance
Severe Hepatic Impairment vs Normal Hepatic Function Matched to Severe Hepatic Function.: Geometric Mean Ratio: 0.929 (90% CI 0.581 to 1.488), Mixed effect analysis of variance

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

Primary outcome: Unbound Brexpiprazole AUC Calculated From Time Zero to Infinity (AUC∞,u)

Time frame: Day 1 to Day 8. Mean (Standard Deviation). Unit: ng*h/mL

Measure	Mild Hepatic Impairment n = 7	Normal Hepatic Function Matched to Mild Hepatic Function. n = 6	Moderate Hepatic Impairment. n = 7	Normal Hepatic Function Matched to Moderate Hepatic Function. n = 7	Severe Hepatic Function n = 3	Normal Hepatic Function Matched to Severe Hepatic Function. n = 5
Value	8.59 (5.29)	5.85 (3.11)	8.50 (2.17)	5.62 (3.13)	3.49 (0.848)	3.36 (0.871)

Mild Hepatic Impairment vs Normal Hepatic Function Matched to Mild Hepatic Function.: Geometic Mean Ratio: 1.255 (90% CI 0.702 to 2.244), Mixed effect analysis of variance
Moderate Hepatic Impairment. vs Normal Hepatic Function Matched to Moderate Hepatic Function.: Geometric Mean Ratio: 1.727 (90% CI 0.977 to 3.052), Mixed effect analysis of variance
Severe Hepatic Function vs Normal Hepatic Function Matched to Severe Hepatic Function.: Geometic Mean Ratio: 1.041 (90% CI 0.506 to 2.142), Mixed effect analysis of variance

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

Primary outcome: Unbound Maximum Plasma Concentration of Brexpiprazole (Cmax,u)

Time frame: Day 1 to Day 8. Mean (Standard Deviation). Unit: ng/mL

Measure	Mild Hepatic Impairment n = 8	Normal Hepatic Function Matched to Mild Hepatic Function. n = 8	Moderate Hepatic Impairment n = 8	Normal Hepatic Function Matched to Moderate Hepatic Function. n = 8	Severe Hepatic Impairment n = 6	Normal Hepatic Function Matched to Severe Hepatic Function. n = 6
Value	0.104 (0.0259)	0.114 (0.0270)	0.0648 (0.0143)	0.0779 (0.0224)	0.0392 (0.0105)	0.0760 (0.0258)

Mild Hepatic Impairment vs Normal Hepatic Function Matched to Mild Hepatic Function.: Geometric Mean Ratio: 0.904 (90% CI 0.707 to 1.156), Mixed effect analysis of variance
Moderate Hepatic Impairment vs Normal Hepatic Function Matched to Moderate Hepatic Function.: Geometric Mean Ratio: 0.850 (90% CI 0.665 to 1.087), Mixed effect analysis of variance
Severe Hepatic Impairment vs Normal Hepatic Function Matched to Severe Hepatic Function.: Geometric Mean Ratio: 0.531 (90% CI 0.399 to 0.705), Mixed effect analysis of variance

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

24 secondary outcomes are reported in the full results.

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.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Mild Hepatic Impairment	0 of 8 (0%)	3 of 8 (37.5%)	Not reported
Moderate Hepatic Impairment	0 of 8 (0%)	3 of 8 (37.5%)	Not reported
Severe Hepatic Impairment	0 of 6 (0%)	1 of 6 (16.7%)	Not reported
Normal Hepatic Function	0 of 23 (0%)	6 of 23 (26.1%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 20 Oct 2015.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

3 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing OPC-34712 in people with Schizophrenia, run by Otsuka Pharmaceutical Development & Commercialization, Inc. at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 3 Sep 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Unbound Brexpiprazole Area Under the Concentration Time Curve (AUC) Calculated to the Last Observable Concentration at Time t (AUCt,u) (time frame: Day 1 to Day 8). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01299454.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Oct 2015.