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Trial record 56 of 64 for:    brexpiprazole

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

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ClinicalTrials.gov Identifier: NCT01289080
Recruitment Status : Completed
First Posted : February 3, 2011
Results First Posted : October 29, 2015
Last Update Posted : October 29, 2015
Sponsor:
Information provided by (Responsible Party):
Otsuka Pharmaceutical Development & Commercialization, Inc.

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Schizophrenia
Psychiatric Disorders
Intervention Drug: OPC-34712
Enrollment 19
Recruitment Details The trial was an open-label, multicenter, parallel-arm, single-dose trial in two groups: 1 group of participants with normal renal function and 1 group of severely renally impaired participants.
Pre-assignment Details 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 Title Normal Renally Impaired
Hide Arm/Group Description Participants with normal renal function were administered 3 mg brexpiprazole on Day 1. Participants with severe renal impairment were administered 3 mg brexpiprazole on Day 1.
Period Title: Overall Study
Started 9 10
Completed 9 10
Not Completed 0 0
Arm/Group Title Normal Renally Impaired Total
Hide Arm/Group Description Participants with normal renal function were administered 3 mg brexpiprazole on Day 1. Participants with severe renal impairment were administered 3 mg brexpiprazole on Day 1. Total of all reporting groups
Overall Number of Baseline Participants 9 10 19
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 9 participants 10 participants 19 participants
58.8  (10.1) 62.9  (12.2) 60.9  (11.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants 10 participants 19 participants
Female
3
  33.3%
3
  30.0%
6
  31.6%
Male
6
  66.7%
7
  70.0%
13
  68.4%
1.Primary Outcome
Title Unbound Area Under the Concentration (AUC) Time Curve Calculated to the Last Observable Concentration Brexpiprazole (AUCt,u).
Hide Description 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.
Time Frame Day 1 to Day 8
Hide Outcome Measure Data
Hide Analysis Population Description
The dataset for pharmacokinetics (PK) analysis of all evaluable brexpiprazole PK parameters consisted of enrolled participants who had evaluable plasma concentrations.
Arm/Group Title Normal Renally Impaired
Hide Arm/Group Description:
Participants with normal renal function were administered 3 mg brexpiprazole on Day 1.
Participants with severe renal impairment were administered 3 mg brexpiprazole on Day 1.
Overall Number of Participants Analyzed 9 10
Mean (Standard Deviation)
Unit of Measure: nanograms*hours/mL (ng*h/mL)
8.17  (1.37) 13.3  (6.26)
2.Primary Outcome
Title Unbound Area Under AUC- Time Curve From Time Zero to Infinity (AUC∞,u).
Hide Description 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.
Time Frame Day 1 to Day 8
Hide Outcome Measure Data
Hide Analysis Population Description
The dataset for PK analysis of all evaluable brexpiprazole PK parameters consisted of enrolled participants who had evaluable plasma concentrations.
Arm/Group Title Normal Renally Impaired
Hide Arm/Group Description:
Participants with normal renal function were administered 3 mg brexpiprazole on Day 1.
Participants with severe renal impairment were administered 3 mg brexpiprazole Day 1.
Overall Number of Participants Analyzed 7 7
Mean (Standard Deviation)
Unit of Measure: ng*h/mL
9.58  (2.26) 18.0  (8.72)
3.Primary Outcome
Title Unbound Maximum (Peak) Plasma Concentration of Brexpiprazole (Cmax,u).
Hide Description 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.
Time Frame Day 1 to Day 8
Hide Outcome Measure Data
Hide Analysis Population Description
The dataset for PK analysis of all evaluable brexpiprazole PK parameters consisted of enrolled participants who had evaluable plasma concentrations.
Arm/Group Title Normal Renally Impaired
Hide Arm/Group Description:
Participants with normal renal function were administered 3 mg brexpiprazole on Day 1.
Participants with severe renal impairment were administered 3 mg brexpiprazole on Day 1.
Overall Number of Participants Analyzed 9 10
Mean (Standard Deviation)
Unit of Measure: ng/mL
0.195  (0.0662) 0.198  (0.0702)
4.Secondary Outcome
Title AUC Time Curve of Brexpiprazole Metabolite (DM-3411) Calculated to the Last Observable Concentration at Time t (AUCt).
Hide Description 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.
Time Frame Day 1 to Day 8
Hide Outcome Measure Data
Hide Analysis Population Description
The dataset for PK analysis of all evaluable brexpiprazole PK parameters consisted of enrolled participants who had evaluable plasma concentrations.
Arm/Group Title Normal Renally Impaired
Hide Arm/Group Description:
Participants with normal renal function were administered 3 mg brexpiprazole on Day 1.
Participants with severe renal impairment were administered 3 mg brexpiprazole on Day 1.
Overall Number of Participants Analyzed 9 9
Mean (Standard Deviation)
Unit of Measure: ng*h/mL
1410  (423) 2080  (1230)
5.Secondary Outcome
Title AUC Time Curve of Brexpiprazole From Time Zero to Infinity (AUC∞).
Hide Description 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 AUC∞ was estimated using the linear trapezoidal rule.
Time Frame Day 1 to Day 8
Hide Outcome Measure Data
Hide Analysis Population Description
The dataset for PK analysis of all evaluable brexpiprazole PK parameters consisted of enrolled participants who had evaluable plasma concentrations. AUC-time curve from zero to infinity (AUC∞) was not determined for DM-3411 metabolite.
Arm/Group Title Normal Renally Impaired
Hide Arm/Group Description:
Participants with normal renal function were administered 3 mg brexpiprazole on Day 1.
Participants with severe renal impairment were administered 3 mg brexpiprazole on Day 1.
Overall Number of Participants Analyzed 7 7
Mean (Standard Deviation)
Unit of Measure: ng*h/mL
2050  (510) 3800  (1970)
6.Secondary Outcome
Title Maximum Plasma Concentration of Brexpiprazole Metabolite (DM-3411) (Cmax).
Hide Description 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.
Time Frame Day 1 to Day 8
Hide Outcome Measure Data
Hide Analysis Population Description
The dataset for PK analysis of all evaluable brexpiprazole PK parameters consisted of enrolled participants who had evaluable plasma concentrations.
Arm/Group Title Normal Renally Impaired
Hide Arm/Group Description:
Participants with normal renal function were administered 3 mg brexpiprazole on Day 1.
Participants with severe renal impairment were administered 3 mg brexpiprazole Day 1.
Overall Number of Participants Analyzed 9 10
Mean (Standard Deviation)
Unit of Measure: ng/mL
18.2  (6.24) 19.8  (12.3)
7.Secondary Outcome
Title Time to Cmax of Brexiprazole Metabolite (DM-3411) (Tmax).
Hide Description 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. Tmax is the time taken to reach highest measured concentration of the drug during the dosing interval.
Time Frame Day 1 to Day 8
Hide Outcome Measure Data
Hide Analysis Population Description
The dataset for PK analysis of all evaluable brexpiprazole PK parameters consisted of enrolled participants who had evaluable plasma concentrations.
Arm/Group Title Normal Renally Impaired
Hide Arm/Group Description:
Participants with normal renal function were administered 3 mg brexpiprazole on Day 1.
Participants with severe renal impairment were administered 3 mg brexpiprazole on Day 1.
Overall Number of Participants Analyzed 9 10
Median (Full Range)
Unit of Measure: h
12.0
(8.00 to 24.00)
30.0
(3.00 to 144)
8.Secondary Outcome
Title Apparent Clearance From Plasma After Extravascular Administration of Brexpiprazole (CL/F).
Hide Description The value of CL/F was determined as Dose/AUC∞. Clearance of a drug was a measure of the rate at which a drug was metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) was influenced by the fraction of the dose absorbed. Clearance was estimated from population PK modeling. Drug clearance was a quantitative measure of the rate at which a drug substance was removed from the blood.
Time Frame Day 1 to Day 8
Hide Outcome Measure Data
Hide Analysis Population Description
The dataset for PK analysis of all evaluable brexpiprazole PK parameters consisted of enrolled participants who had evaluable plasma concentrations.
Arm/Group Title Normal Renally Impaired
Hide Arm/Group Description:
Participants with normal renal function were administered 3 mg brexpiprazole on Day 1.
Participants with severe renal impairment were administered 3 mg brexpiprazole on Day 1.
Overall Number of Participants Analyzed 7 7
Mean (Standard Deviation)
Unit of Measure: mL/h/kg
23.0  (8.05) 14.2  (6.46)
9.Secondary Outcome
Title Unbound Fraction of Brexpiprazole in Plasma (fu).
Hide Description 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.
Time Frame Day 1 to Day 8
Hide Outcome Measure Data
Hide Analysis Population Description
The dataset for PK analysis of all evaluable brexpiprazole PK parameters consisted of enrolled participants who had evaluable plasma concentrations.
Arm/Group Title Normal Renally Impaired
Hide Arm/Group Description:
Participants with normal renal function were administered 3 mg brexpiprazole on Day 1.
Participants with severe renal impairment were administered 3 mg brexpiprazole on Day 1.
Overall Number of Participants Analyzed 9 10
Mean (Standard Deviation)
Unit of Measure: % of unbound brexpiprazole in plasma
0.476  (0.0525) 0.492  (0.0346)
10.Secondary Outcome
Title Apparent Unbound Clearance From Plasma After Extravascular Administration of Brexpiprazole (CLu/F).
Hide Description 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.
Time Frame Day 1 to Day 8
Hide Outcome Measure Data
Hide Analysis Population Description
The dataset for PK analysis of all evaluable brexpiprazole PK parameters consisted of enrolled participants who had evaluable plasma concentrations.
Arm/Group Title Normal Renally Impaired
Hide Arm/Group Description:
Participants with normal renal function were administered 3 mg brexpiprazole on Day 1.
Participants with severe renal impairment were administered 3 mg brexpiprazole on Day 1.
Overall Number of Participants Analyzed 7 7
Mean (Standard Deviation)
Unit of Measure: mL/h/kg
0.110  (0.0493) 0.0686  (0.0336)
11.Secondary Outcome
Title Terminal-phase Elimination Half-life of Brexpiprazole (t1/2,z).
Hide Description 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.
Time Frame Day 1 to Day 8
Hide Outcome Measure Data
Hide Analysis Population Description
The dataset for PK analysis of all evaluable brexpiprazole PK parameters consisted of enrolled participants who had evaluable plasma concentrations. The terminal phase elimination half-life was not determined for DM-3411 metabolite.
Arm/Group Title Normal Renally Impaired
Hide Arm/Group Description:
Participants with normal renal function were administered 3 mg brexpiprazole on Day 1.
Participants with severe renal impairement were administered 3 mg brexpiprazole on Day 1.
Overall Number of Participants Analyzed 7 7
Mean (Standard Deviation)
Unit of Measure: h
71.7  (23.8) 87.4  (28.9)
12.Secondary Outcome
Title Renal Clearance (CLr) of Brexipiprazole Metabolite (DM-3411).
Hide Description Urine samples were collected at Predose at intervals of 0 to 24, 24 to 48, 48 to 72, 72 to 96, 96 to 120, 120 to 144, and 144 to 168 hours postdose. Unbound fraction of drug in plasma was calculated as 100% - mean percent of brexpiprazole bound to plasma protein for each participant.
Time Frame Day 1 to Day 8
Hide Outcome Measure Data
Hide Analysis Population Description
The dataset for PK analysis of all evaluable brexpiprazole PK parameters consisted of enrolled participants who had evaluable plasma concentrations.
Arm/Group Title Normal Renally Impaired
Hide Arm/Group Description:
Participants with normal renal function were administered 3 mg brexpiprazole on Day 1.
Participants with severe renal impairement were administered 3 mg brexpiprazole on Day 1.
Overall Number of Participants Analyzed 9 9
Mean (Standard Deviation)
Unit of Measure: mL/h/kg
1.38  (0.883) 0.683  (0.471)
13.Secondary Outcome
Title Fraction of the Systemically Available Brexpiprazole Metabolite (DM-3411) Excreted Into the Urine (fe,u).
Hide Description Urine samples were collected at Predose and at intervals of 0 to 24, 24 to 48, 48 to 72, 72 to 96, 96 to 120, 120 to 144, and 144 to 168 hours postdose. Unbound fraction of drug in plasma was calculated as 100% - mean percent of brexpiprazole bound to plasma protein for each participant.
Time Frame Day 1 to Day 8
Hide Outcome Measure Data
Hide Analysis Population Description
The dataset for PK analysis of all evaluable brexpiprazole PK parameters consisted of enrolled participants who had evaluable plasma concentrations.
Arm/Group Title Normal Renally Impaired
Hide Arm/Group Description:
Participants with normal renal function were administered 3 mg brexpiprazole on Day 1.
Participants with severe renal impairement were administered 3 mg brexpiprazole on Day 1.
Overall Number of Participants Analyzed 9 9
Mean (Standard Deviation)
Unit of Measure: % of unbound brexpiprazole in urine.
3.91  (1.66) 2.55  (1.19)
14.Secondary Outcome
Title The Abnormalities Found in Vital Signs, ECGs, and Clinical Laboratory Tests Are Reported as AEs Upon Study Physicians Discretion.
Hide Description An adverse event (AE) was an exacerbation of an existing problem or any new problem, experienced by a participant when enrolled in a trial, whether or not it was considered drug related by the study physician.
Time Frame AEs were recorded from Screening (ICF was signed) to Follow-up 31 (+ 2) days.
Hide Outcome Measure Data
Hide Analysis Population Description
The dataset for all safety analyses consisted of the data from all enrolled participants who received at least 1 dose of study medication, regardless of any protocol deviation. All observed data for these subjects were included.
Arm/Group Title Normal Renally Impaired
Hide Arm/Group Description:
Participants with normal renal function were administered 3 mg brexpiprazole on Day 1.
Participants with severe renal impairement were administered 3 mg brexpiprazole on Day 1.
Overall Number of Participants Analyzed 9 10
Measure Type: Number
Unit of Measure: participants
Participants with adverse events 3 5
Participants with TEAEs 3 5
Participants with severe TEAEs 0 1
Time Frame AEs were recorded from Screening (ICF was signed) to Follow-up 31 (+ 2) days.
Adverse Event Reporting Description A SAE was any untoward medical occurrence that results in death or was life-threatening or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or any new problem, experienced by a participant when enrolled in a trial, whether or not it was considered drug related by the study physician.
 
Arm/Group Title Brexpiprazole 3mg
Hide Arm/Group Description Participants with normal renal function and severe renal impairment were administered 3 mg brexpiprazole.
All-Cause Mortality
Brexpiprazole 3mg
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Brexpiprazole 3mg
Affected / at Risk (%)
Total   0/19 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Brexpiprazole 3mg
Affected / at Risk (%)
Total   8/19 (42.11%) 
Gastrointestinal disorders   
Constipation * 1  1/19 (5.26%) 
Nausea * 1  1/19 (5.26%) 
Infections and infestations   
Upper respiratory tract infection * 1  1/19 (5.26%) 
Nervous system disorders   
Dizziness * 1  1/19 (5.26%) 
Headache * 1  2/19 (10.53%) 
Somnolence * 1  3/19 (15.79%) 
Vascular disorders   
Hypotension * 1  1/19 (5.26%) 
Orthostatic hypotension * 1  2/19 (10.53%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 11.1
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: NCT01289080     History of Changes
Other Study ID Numbers: 331-09-226
First Submitted: February 1, 2011
First Posted: February 3, 2011
Results First Submitted: August 4, 2015
Results First Posted: October 29, 2015
Last Update Posted: October 29, 2015