Trial Evaluating OPC-34712 in Subjects With Normal Renal... | NCT01289080

NCT01289080

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

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No data is available for this block.

Derived Section

Miscellaneous Info Module

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Label	Type	Description	Intervention Names
Group 1	Active Comparator	subjects with normal renal function	Drug: OPC-34712
Group 2	Active Comparator	severely renally impaired subjects	Drug: OPC-34712

Name	Type	Description	Arm Group Labels	Other Names
OPC-34712	Drug	administered orally	Group 1 Group 2

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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

Measure	Description	Time Frame
AUC Time Curve of Brexpiprazole Metabolite (DM-3411) Calculated to the Last Observable Concentration at Time t (AUCt).	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. The AUCt was estimated using the linear trapezoidal rule.	Day 1 to Day 8

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

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.

Inclusion Criteria for Subjects with Normal Renal Function

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.

Inclusion Criteria for Renally Impaired Subjects

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.

Exclusion Criteria:

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.

Exclusion Criteria for Healthy Subjects

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.
Subjects who have supine, sitting, or standing blood pressure, after resting for ≥ 3 minutes, higher than 130/80 mmHg or lower than 100/50 mmHg. The sponsor may allow exceptions if they are not deemed clinically significant.

Exclusion Criteria for Renally Impaired Subjects

Subjects that have undergone a renal transplant.
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.
Clinically significant abnormal findings in the serum chemistry, hematology, or urinalysis results obtained at Screening or Day -1, other than those associated with underlying renal conditions and other stable medical conditions consistent with the disease processes.
Subject requiring dialysis or expected to require dialysis within 45 days.
Subjects who have supine, sitting, or standing blood pressure, after resting for ≥ 3 minutes, higher than 160/95 mmHg or lower than 100/50 mmHg. The sponsor may allow exceptions if they are not deemed clinically significant.
Subjects with evidence of delirium.
Clinically relevant changes on electrocardiogram such as any atrioventricular block, prolongation of the QRS complex over 120 msec (for both male and female subjects), or with a QTcF interval ≥ 450 msec.
Any subject who, in the opinion of the sponsor or the investigator, should not participate in the trial.
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.
Use of any drug known or suspected of inhibiting or stimulating hepatic drug metabolism enzymes within 30 days prior to Screening.
Exposure to any substances known to stimulate hepatic microsomal enzymes within 30 days prior to Screening through the end of the trial (eg, occupational exposure to pesticides, organic solvents).
History of serious mental disorders.
Major surgery of the digestive tract (excluding appendectomy).

Contacts/Locations Module

Name	Affiliation	Role
Aleksandar Skuban	Otsuka Pharmaceutical Development & Commercialization, Inc.	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Otsuka Investigational Site		Miami	Florida	33014	United States
Otsuka Investigational Site

References Module

No data available

No data is available for this block.

IPD Sharing Statement Module

No data available

No data is available for this block.

The participant assignment was made based on Urine Creatinine Clearance (urine CLcr). If the urine CLcr was < 30 mL/minute for renally impaired participants and the urine CLcr was > 80 mL/minute for participants with normal renal function.

Arm/Group Information

ID	Title	Description
FG000	Normal	Participants with normal renal function were administered 3 mg brexpiprazole on Day 1.
FG001	Renally Impaired	Participants with severe renal impairment were administered 3 mg brexpiprazole on Day 1.

Periods

Title

Milestones

Reasons Not Completed

Overall Study

Type	Comment	Milestone Data
STARTED		FG0009 subjects FG00110 subjects
COMPLETED		FG0009 subjects FG00110 subjects
NOT COMPLETED		FG0000 subjects FG0010 subjects

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Normal	Participants with normal renal function were administered 3 mg brexpiprazole on Day 1.
BG001	Renally Impaired	Participants with severe renal impairment were administered 3 mg brexpiprazole on Day 1.

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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.

The dataset for pharmacokinetics (PK) analysis of all evaluable brexpiprazole PK parameters consisted of enrolled participants who had evaluable plasma concentrations.

Posted

Mean

Standard Deviation

nanograms*hours/mL (ng*h/mL)

Day 1 to Day 8

ID	Title	Description
OG000	Normal	Participants with normal renal function were administered 3 mg brexpiprazole on Day 1.

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Brexpiprazole 3mg	Participants with normal renal function and severe renal impairment were administered 3 mg brexpiprazole.

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Constipation	Gastrointestinal disorders	MedDRA 11.1	Non-systematic Assessment

More Info Module

Certain Agreements

Title	Organization	Phone	Extension	Email
Global Medical Affairs	Otsuka Pharmaceutical Development and Commercialization, Inc.	800 562-3974

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

ID	Term
D012559	Schizophrenia
D001523	Mental Disorders
D051437	Renal Insufficiency

ID	Term
D019967	Schizophrenia Spectrum and Other Psychotic Disorders
D007674	Kidney Diseases
D014570	Urologic Diseases
D052776	Female Urogenital Diseases

Intervention Browse Module

No data available

No data is available for this block.

Masking Info

EG0001 affected19 at risk