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

NCT01299454 | Completed Phase 1 Results

• 1 other identifier: 331-09-225
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 3

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.

Conditions

Schizophrenia

Outcome Measures

Primary Outcomes (3)

• 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).

  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 - ∞).

  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.

  Day 1 to Day 8

Secondary Outcomes (24)

• Area Under the Curve of Brexpiprazole Calculated to the Last Observable Concentration at Time t (AUCt)

  Day 1 to Day 8

• Area Under the Concentration Time Curve of Brexpiprazole From Time Zero to Infinity (AUC∞)

  Day 1 to Day 8

• Maximum Plasma Concentration of Brexpiprazole (Cmax)

  Day 1 to Day 8

• Time to Cmax of Brexiprazole (Tmax)

  Day 1 to Day 8

• Apparent Clearance of Brexpiprazole From Plasma After Extravascular Administration (CL/F)

  Day 1 to Day 8

Study Arms (4)

Normal

ACTIVE COMPARATOR

Drug: OPC-34712

Mild

ACTIVE COMPARATOR

Drug: OPC-34712

Moderate

ACTIVE COMPARATOR

Drug: OPC-34712

Severe

ACTIVE COMPARATOR

Drug: OPC-34712

Interventions

OPC-34712 DRUG

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.

Mild; Moderate; Normal; Severe

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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).
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Otsuka Pharmaceutical Development & Commercialization, Inc.: lead

Study Sites (3)

Study Site

Miami, Florida, 33014, United States

Location

Study Site

Minneapolis, Minnesota, 55404, United States

Location

Study Site

San Antonio, Texas, 78212, United States

Location

MeSH Terms

Conditions

Schizophrenia

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Results Point of Contact

• Title: Global Medical Affairs
• Organization: Otsuka Pharmaceutical Development and Commercialization, Inc.

800-562-3974

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 16, 2011
• First Posted: February 18, 2011
• Study Start: December 1, 2010
• Primary Completion: June 1, 2011
• Study Completion: July 1, 2011
• Last Updated: October 20, 2015
• Results First Posted: September 3, 2015

Record last verified: 2015-09

Locations

US (3)