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: November 6, 2013
Last verified: November 2013
  Purpose

The purpose of this study is to assess the safety and tolerability of ascending multiple oral doses of brexpiprazole as adjunctive therapy in the treatment of elderly subjects with MDD.


Condition Intervention Phase
Major Depressive Disorder
Drug: Brexpiprazole
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 1, Multicenter, Randomized, Double-blind, Sequential Cohort, Placebo-controlled Trial to Assess the Safety and Tolerability of Ascending Multiple Oral Doses of Brexpiprazole as Adjunctive Therapy in the Treatment of Elderly Subjects With Major Depressive Disorder

Resource links provided by NLM:


Further study details as provided by Otsuka Pharmaceutical Development & Commercialization, Inc.:

Primary Outcome Measures:
  • Simpson-Angus Scale Total Score - Mean Change from baseline to study completion [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    Simpson-Angus Scale Total Score - Mean Change from baseline to study completion

  • Tolerability [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    Brexpiprazole will be judged to be tolerated if 6 out of 8 (75%) subejcts in a test cohort tolerate the dose after 14 days of QD dosing at the end of the fixed dose phase based on the blinded data.

  • Number of Adverse Events [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    number of adverse evetns reported

  • Barnes Akathisia Global Score - Mean Change from baseline to study completion [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    Barnes Akathisia Global Score - Mean Change from baseline to study completion

  • AIMS Movement Rating Score - Mean Change from baseline to study completion [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    AIMS Movement Rating Score - Mean Change from baseline to study completion

  • Columbia-Suicide Severity Rating Scale (C-SSRS) - Mean Change from Baseline to study completion [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    Columbia-Suicide Severity Rating Scale (C-SSRS) - Mean Change from Baseline to study completion

  • Laboratory Values of Potential Clinical Relevance - Mean Change from Baseline to study completion [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    Laboratory Values of Potential Clinical Relevance - Mean Change from Baseline to study completion

  • Vital Signs of Potential Clinical Relevance - Mean Change from Baseline to study completion [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    Vital Signs of Potential Clinical Relevance - Mean Change from Baseline to study completion

  • ECG Measurements of Potential Clinical Relevance - Mean Change from Baseline to study completion [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    ECG Measurements of Potential Clinical Relevance - Mean Change from Baseline to study completion


Enrollment: 18
Study Start Date: July 2012
Study Completion Date: May 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1
14 day titration phase and two fixed dose phases. The first fixed dose phase is 14 days with a daily dose of 2mg brexpiprazole/placebo. The second fixed dose phase is 14 days with a daily dose of 3 mg brexpiprazole/placebo.
Drug: Brexpiprazole
up to 3mg oral dose once daily
Experimental: Cohort 2
14 day titration phase and a 14 day fixed dose phase a daily dose of 3mg brexpiprazole/placebo.
Drug: Brexpiprazole
up to 3mg oral dose once daily
Experimental: Cohort 3
21 day titration phase and a 14 day fixed dose phase a daily dose of 3mg brexpiprazole/placebo.
Drug: Brexpiprazole
up to 3mg oral dose once daily
Placebo Comparator: Placebo
Placebo
Drug: Placebo

Detailed Description:

This is a phase 1, multicenter, randomized, double-blind, placebo-controlled, multiple ascending dose trial in 3 sequential cohorts of elderly subjects (age 70 to 85 years old) with MDD. Brexpiprazole will be administered as an adjunct treatment to the current antidepressant therapy that the subject is receiving. Total individual subject duration is expected to be no more than 119 days (a 30-day screening period, a 14-day washout period, up to 45-day in-clinic treatment period, and a 30-day follow-up after the last dose of trial medication).

  Eligibility

Ages Eligible for Study:   70 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects who are able to provide written informed consent
  • Ability to understand the nature of the trial and follow protocol requirements
  • Male and female patients 70 to 85 years of age
  • Subjects with normal or clinically stable findings on physical examination, medical history, clinical laboratory determinations, ECGs in relation to age
  • BMI of 18 to 35 kg/m2.
  • Stable subjects with a principal psychiatric diagnosis of MDD
  • Subjects willing to discontinue all prohibited psychotropic and other prohibited medication

Exclusion Criteria:

  • Sexually active males who are not practicing 2 different methods of birth control during the trial and for 30 days after the last dose of trial medication or who will not remain abstinent during the trial and for 30 days after the last dose
  • Subjects who have had a vagus nerve stimulation device implanted or who have received ECT within 6 months of Screening
  • Subjects with a current Axis I (DSM-IV-TR) diagnosis of:

    • Delirium, dementia, amnestic, or other cognitive disorder
    • Eating disorder (including anorexia nervosa or bulimia)
    • Obsessive-compulsive disorder
    • Panic disorder
    • Posttraumatic stress disorder or current or prior Axis I (DSM-IV-TR) diagnosis of Schizophrenia, schizoaffective disorder, or other psychotic disorder, Bipolar I or II disorder or bipolar disorder not otherwise specified
  • Subjects with a clinically significant current Axis II (DSM-IV-TR) diagnosis of borderline, antisocial, paranoid, schizoid, schizotypal, or histrionic personality disorder
  • Subjects experiencing hallucinations, delusions, or any psychotic symptomatology
  • Subjects who have Active Suicidal Ideation with Some Intent to Act and whose most recent episode occurred within the last 6 months
  • Subjects who have met DSM-IV-TR criteria for substance abuse or dependence within the past 180 days
  • Subjects with hypothyroidism or hyperthyroidism and/or an abnormal result for free T4 at Screening
  • Subjects who currently have clinically significant neurological, hepatic, renal, metabolic, hematological, immunological, cardiovascular, pulmonary, or gastrointestinal disorders
  • Subjects with IDDM
  • Subjects with uncontrolled hypertension (DBP > 95 mmHg) or symptomatic hypotension
  • Subjects with epilepsy, a history of epilepsy, or a history of seizure
  • Subjects with a positive drug screen for cocaine or other drugs of abuse
  • The following laboratory test and ECG results are exclusionary:

    1. Platelets ≤ 75,000/mm3
    2. Hemoglobin ≤ 9 g/dL
    3. Neutrophils, absolute ≤ 1000/mm3
    4. AST > 3 × upper limit of normal
    5. ALT > 3 × upper limit of normal
    6. Creatinine ≥ 2 mg/dL
    7. HbA1c ≥ 7%
    8. QTcF ≥ 450 msec
  • Treatment with a MAOI within the 2 weeks prior to the first dose of trial medication
  • Use of benzodiazepines and/or hypnotics within 1 week prior the first dose of trial medication
  • Use of oral neuroleptics within 30 days prior to or long-acting approved neuroleptics ≤ 1 full cycle plus 14 days prior to the first dose of trial medication on Day 1
  • Prohibited concomitant medications used prior to randomization or anticipated need for such medications during the trial
  • Subjects who would be likely to require prohibited concomitant therapy during the trial
  • Subjects who received brexpiprazole in any prior clinical trial
  • Subjects with a history of neuroleptic malignant syndrome
  • Subjects with a history of true allergic response to more than 1 class of medications
  • Prisoners or subjects who are compulsorily detained for treatment of either a psychiatric or physical illness
  • Subjects who participated in a clinical trial within the last 180 days or who participated in more than 2 clinical trials within the past year.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01670279

Locations
United States, Florida
Accurate Clinical Trials
Kissimmee, Florida, United States
Miami Jewish Health System
Miami, Florida, United States
United States, Missouri
St. Louis Clinical Trials
St. Louis, Missouri, United States
United States, Pennsylvania
CRI Lifetree- Philadelphia Research Center
Philadelphia, Pennsylvania, United States
Sponsors and Collaborators
Otsuka Pharmaceutical Development & Commercialization, Inc.
H. Lundbeck A/S
Investigators
Study Director: James M. Youakim, MD Otsuka Pharmaceutical Development & Commercialization, Inc.
  More Information

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
Last Updated: November 6, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Otsuka Pharmaceutical Development & Commercialization, Inc.:
Major Depressive Disorder (MDD)

Additional relevant MeSH terms:
Depressive Disorder
Depression
Depressive Disorder, Major
Mood Disorders
Mental Disorders
Behavioral Symptoms

ClinicalTrials.gov processed this record on July 31, 2014