Trial Evaluating OPC-34712 in Subjects With Normal Renal Function and Renally Impaired Subjects

NCT01289080 | Completed Phase 1 Results DMC

• 1 other identifier: 331-09-226
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 2

Brief Summary

This trial is an open-label, multi-center, parallel-arm, single-dose trial in 2 groups: 1 group of subjects with normal renal function and 1 group of severely renally impaired subjects.

Conditions

Schizophrenia; Psychiatric Disorders

Keywords

Schizophrenia; psychiatric disorders; renal failure

Outcome Measures

Primary Outcomes (3)

• Unbound Area Under the Concentration (AUC) Time Curve Calculated to the Last Observable Concentration Brexpiprazole (AUCt,u).

  Blood samples were collected on Day 1 at Predose (within 15 minutes of dosing) and at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours Postdose or at Early Termination (ET). Unbound fraction of drug in plasma was calculated as 100% - mean percent of brexpiprazole bound to plasma protein for each participant.

  Day 1 to Day 8

• Unbound Area Under AUC- Time Curve From Time Zero to Infinity (AUC∞,u).

  Blood samples were collected at Predose (within 15 minutes of dosing) and at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours or at ET. Unbound fraction of drug in plasma was calculated as 100% - mean percent of brexpiprazole bound to plasma protein for each participant.

  Day 1 to Day 8

• Unbound Maximum (Peak) Plasma Concentration of Brexpiprazole (Cmax,u).

  Blood samples were collected at Predose (within 15 minutes of dosing) and at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours or at ET. Unbound fraction of drug in plasma was calculated as 100% - mean percent of brexpiprazole bound to plasma protein for each participant.

  Day 1 to Day 8

Secondary Outcomes (11)

• AUC Time Curve of Brexpiprazole Metabolite (DM-3411) Calculated to the Last Observable Concentration at Time t (AUCt).

  Day 1 to Day 8

• AUC Time Curve of Brexpiprazole From Time Zero to Infinity (AUC∞).

  Day 1 to Day 8

• Maximum Plasma Concentration of Brexpiprazole Metabolite (DM-3411) (Cmax).

  Day 1 to Day 8

• Time to Cmax of Brexiprazole Metabolite (DM-3411) (Tmax).

  Day 1 to Day 8

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

  Day 1 to Day 8

Study Arms (2)

Group 1

ACTIVE COMPARATOR

subjects with normal renal function

Drug: OPC-34712

Group 2

ACTIVE COMPARATOR

severely renally impaired subjects

Drug: OPC-34712

Interventions

OPC-34712 DRUG

administered orally

Group 1; Group 2

Eligibility Criteria

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

You may qualify if:

• Male or female (non-childbearing potential) subjects ≥ 18 years of age.
• Ability to provide written informed consent prior to initiation of any trial-related procedures, and ability, in the opinion of the principal investigator, to comply with all the requirements of the trial.
• Male and female subjects who are surgically sterile; female subjects who have been postmenopausal for at least 12 consecutive months (confirmed by follicle stimulating hormone sample at Screening); or male subjects who agree to remain abstinent or to practice double-barrier forms of birth control and refrain from sperm donation from trial Screening through 90 days from the last dose of the investigational medicinal product.
• Body weight within ± 35% of ideal body weight as defined in the 1983 Metropolitan Height and Weight Tables (see Appendix 4, Appendix 5, and Appendix 6). Minimum body weight no less than 50 kg.
• Subjects who are in good health as determined by a medical history, physical examination, serum chemistry, hematology, urinalysis, hepatitis B and C tests, and human immunodeficiency virus (HIV) testing.
• Creatinine clearance \> 80 mL/min indicating normal renal function.
• Renally impaired subjects may be taking medications which, in the opinion of the clinical investigator and sponsor, are believed to be therapeutic for the subjects (but do not affect OPC-34712 absorption, distribution, metabolism, or elimination). Inhibitors and inducers of CYP3A4 and inhibitors of CYP2D6 are not allowed.
• Creatinine clearance \< 30 mL/min indicating severe renal impairment.
• Subjects with renal impairment should have relatively stable renal function as determined by creatinine clearance and otherwise be in generally good health.

You may not qualify if:

• Clinically significant abnormality in past medical history, or at the screening physical examination, that in the investigator's or sponsor's opinion may place the subject at risk or interfere with outcome variables including absorption, distribution, metabolism, and excretion of drug.
• Any surgical or medical condition (active or chronic) that may interfere with drug absorption, distribution, metabolism, or excretion, or any other condition that may place the subject at risk.
• History of drug and/or alcohol abuse within 2 years prior to Screening.
• A positive urine alcohol test and/or urine drug screen for substance of abuse at Screening or upon check-in to the trial site.
• The donation of blood or plasma within 30 days prior to dosing.
• Any history of significant bleeding or hemorrhagic tendencies.
• History of or current hepatitis or carriers of hepatitis B surface antigen (HBsAg) and/or hepatitis C antibodies (anti-HCV).
• History of acquired immunodeficiency syndrome or determined human immunodeficiency virus (HIV) positive at Screening.
• Use of an investigational drug or product, or participation in a drug trial within 30 days prior to dosing.
• Previous exposure to OPC-34712.
• History of clinically significant drug allergies or sensitivities.
• Subjects who are pregnant or breastfeeding. A negative serum pregnancy test must be confirmed prior to administration of trial medication for all female subjects.
• Subjects who have a supine pulse rate, after resting for ≥ 3 minutes, outside the range of 40 to 90 bpm. The sponsor may allow exceptions if they are not deemed clinically significant.
• Clinically significant abnormal findings in the serum chemistry, hematology, or urinalysis results obtained at Screening or Day -1.
• 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. The sponsor may allow exceptions only if the medication's administration is deemed unlikely to impact the pharmacokinetic result. Inhibitors and inducers of CYP3A4 and inhibitors of CYP2D6 are not allowed.

Sponsors & Collaborators

• Otsuka Pharmaceutical Development & Commercialization, Inc.: lead

Study Sites (2)

Otsuka Investigational Site

Miami, Florida, 33014, United States

Location

Otsuka Investigational Site

Minneapolis, Minnesota, 55404, United States

Location

MeSH Terms

Conditions

Schizophrenia; Mental Disorders; Renal Insufficiency

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Results Point of Contact

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

800 562-3974

Study Officials

• Aleksandar Skuban

  Otsuka Pharmaceutical Development & Commercialization, Inc.

  STUDY DIRECTOR

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 1, 2011
• First Posted: February 3, 2011
• Study Start: January 1, 2011
• Primary Completion: December 1, 2011
• Study Completion: January 1, 2012
• Last Updated: October 29, 2015
• Results First Posted: October 29, 2015

Record last verified: 2015-09

Locations

US (2)