Phase 1 Study to Assess the Safety/Tolerability of Brexpiprazole as Adjunctive Therapy in Elderly Subjects With Major Depressive Disorder

This study has been completed.
Sponsor:
Collaborator:
H. Lundbeck A/S
Information provided by (Responsible Party):
Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier:
NCT01670279
First received: August 7, 2012
Last updated: January 5, 2016
Last verified: January 2016
Results First Received: August 4, 2015  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Major Depressive Disorder
Interventions: Drug: Brexpiprazole
Drug: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
This was a phase 1, multicenter, randomized, double-blind, placebo-controlled, multiple ascending dose trial planned in 3 sequential cohorts of elderly participants (70 to 85 years old) with major depressive disorder (MDD). Brexpiprazole was administered as an adjunct treatment to the current antidepressant therapy that the participant received.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
The study included a 30-day screening period, a 14-day washout period, up to 45-day inpatient treatment period (titration: received brexpiprazole or placebo once daily [QD] for 14 or 21 days and fixed dose phase: received assigned fixed dose for 14 or 28 days), and a 30-day follow-up after the last dose of study drug.

Reporting Groups
  Description
Brexpiprazole-Cohort 1 In the titration phase, participants received 0.5 mg brexpiprazole QD for 7 days, followed by 1 mg brexpiprazole QD for 7 days. In the fixed dose phase, participants received 2 mg brexpiprazole QD for 14 days, followed by 3 mg brexpiprazole QD for 14 days.
Brexpiprazole-Cohort 2 In the titration phase, participants received 0.5 mg brexpiprazole QD for 7 days, followed by 1 mg brexpiprazole QD for 7 days. In the fixed dose phase, participants received 3 mg brexpiprazole QD for 14 days.
Brexpiprazole-Cohort 3 In the titration phase, participants were to receive 0.5 mg brexpiprazole or placebo QD for 7 days, followed by 1 mg brexpiprazole or placebo QD for 7 days, and then 2 mg brexpiprazole or placebo QD for 7 days. In the fixed dose phase, participants were to receive 3 mg brexpiprazole or placebo QD for 14 days. However, Cohort 3 was not conducted due to safety and tolerability results from Cohorts 1 and 2.
Placebo In the titration phase, participants received 0.5 mg placebo QD for 7 days, followed by 1 mg placebo QD for 7 days. In the fixed dose phase, Cohort 1: participants received 2 mg placebo QD for 14 days, followed by 3 mg placebo QD for 14 days. Cohort 2: participants received 3 mg placebo QD for 14 days.

Participant Flow:   Overall Study
    Brexpiprazole-Cohort 1     Brexpiprazole-Cohort 2     Brexpiprazole-Cohort 3     Placebo  
STARTED     6     7     0     5  
COMPLETED     6     5     0     4  
NOT COMPLETED     0     2     0     1  
Adverse Event                 0                 1                 0                 0  
Physician Decision                 0                 1                 0                 0  
Participant met withdrawal criteria                 0                 0                 0                 1  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Brexpiprazole-Cohort 1 In the titration phase, participants received 0.5 mg brexpiprazole QD for 7 days, followed by 1 mg brexpiprazole QD for 7 days. In the fixed dose phase, participants received 2 mg brexpiprazole QD for 14 days, followed by 3 mg brexpiprazole QD for 14 days.
Brexpiprazole-Cohort 2 In the titration phase, participants received 0.5 mg brexpiprazole QD for 7 days, followed by 1 mg brexpiprazole QD for 7 days. In the fixed dose phase, participants received 3 mg brexpiprazole QD for 14 days.
Placebo In the titration phase, participants received 0.5 mg placebo QD for 7 days, followed by 1 mg placebo QD for 7 days. In the fixed dose phase, Cohort 1: participants received 2 mg placebo QD for 14 days, followed by 3 mg placebo QD for 14 days. Cohort 2: participants received 3 mg placebo QD for 14 days.
Total Total of all reporting groups

Baseline Measures
    Brexpiprazole-Cohort 1     Brexpiprazole-Cohort 2     Placebo     Total  
Number of Participants  
[units: participants]
  6     7     5     18  
Age  
[units: Years]
Mean (Standard Deviation)
  73.2  (4.0)     76.0  (5.3)     72.6  (1.5)     74.1  (4.2)  
Gender  
[units: participants]
       
Female     4     5     4     13  
Male     2     2     1     5  



  Outcome Measures
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1.  Primary:   Number of Participants Who Tolerated Brexpiprazole   [ Time Frame: 45 Days ]

2.  Primary:   Number of AEs Reported.   [ Time Frame: Throughout the study, up to 119 days ]

3.  Primary:   Incidence of Laboratory Values of Potential Clinical Significance   [ Time Frame: Titration Day 7, Fixed dose Day 14 and 28 and Last Visit ]

4.  Primary:   Incidence of Vital Signs of Potential Clinical Significance   [ Time Frame: Baseline, Titration Day 1, 2, 7, 8, Fixed Days 1, 2, 14, 15, 28, 29, Early Termination and Last Visit. ]

5.  Primary:   Incidence of ECG Evaluations of Potential Clinical Significance   [ Time Frame: Titratrion Day 1 and 7, Fixed dose Day 1, 14, 28, Early Termination ]

6.  Primary:   Incidence of Physical Examination Evaluation of Potential Clinical Significance   [ Time Frame: Physical examination was performed at Screening, check-in, and discharge ]

7.  Primary:   Mean Change From Baseline to Study Completion in Simpson-Angus Scale (SAS) Total Score   [ Time Frame: End of Titration, Day 15, Day 29, Early Termination and Last visit ]

8.  Primary:   Mean Change From Baseline to Study Completion in Barnes Akathisia Global Score   [ Time Frame: End of Titration, Day 15, Day 29, Early Termination and Last visit ]

9.  Primary:   Mean Change From Baseline to Study Completion in Abnormal Involuntary Movement Scale (AIMS) Rating Score.   [ Time Frame: End of Titration, Day 15, Day 29, Early Termination and Last visit ]

10.  Primary:   Change From Baseline to Study Completion in C-SSRS Score.   [ Time Frame: Baseline, End of Titration, Fixed dose Day 14 and 28, Day 15 and 29, Early Termination, Last Visit ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Cohort 3 was not initiated based on the safety/tolerability results from Cohorts 1 and 2.


  More Information
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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


No publications provided


Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier: NCT01670279     History of Changes
Other Study ID Numbers: 331-12-291
Study First Received: August 7, 2012
Results First Received: August 4, 2015
Last Updated: January 5, 2016
Health Authority: United States: Food and Drug Administration