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

NCT01670279 | Completed Phase 1 Results

• 1 other identifier: 331-12-291
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Major Depressive Disorder

Keywords

Major Depressive Disorder (MDD)

Outcome Measures

Primary Outcomes (10)

• Number of Participants Who Tolerated Brexpiprazole

  Safety and tolerability of brexpiprazole was noted to be primary outcome measure. Brexpiprazole was judged to be tolerated if at least 6 out of 8 (75%) of the participants in a test cohort tolerated the dose after 14 days of QD dosing at the end of the fixed dose phase based on the blinded data. Dose toleration was defined as follows: during the course of the trial, the participants did not experience any moderate or severe adverse events (AEs) or potentially clinically relevant changes from Baseline in laboratory values, vital signs, electrocardiogram (ECG) tracings, Columbia-Suicide Severity Rating Scale (C-SSRS), or extrapyramidal symptom (EPS) ratings, which were assessed as possibly related to the study drug, and would have warranted a dose decrease or discontinuation of the study drug. The safety and tolerability of brexpiprazole was defined by parameters: AEs, laboratory values, vital signs, ECG, C-SSRS, or EPS ratings, the results of each of the parameters reported separately.

  45 Days

• Number of AEs Reported.

  The AEs were one of the primary parameters to measure the safety and tolerability of individual participants. The AEs were captured for all participants from the time the ICF was signed until the end of the trial. AEs were measured throughout the 14-day titration and 28-day fixed dose phase until follow-up (30 \[±2\] days after last dose of study medication).

  Throughout the study, up to 119 days

• Incidence of Laboratory Values of Potential Clinical Significance

  The laboratory values were one of the primary parameters to measure the safety and tolerability of individual participants. Incidence of TEAEs of potential clinical relevance include abnormal values in serum chemistry, hematology, urinalyses and prolactin tests that were identified based on pre-defined criteria.

  Titration Day 7, Fixed dose Day 14 and 28 and Last Visit

• Incidence of Vital Signs of Potential Clinical Significance

  The vital signs were one of the primary parameters to measure the safety and tolerability of individual participants. Incidence of TEAEs of potential clinical relevance included abnormal values in heart rate, systolic and diastolic blood pressure, respiratory rate and weight that were identified based on pre-defined criteria.

  Baseline, Titration Day 1, 2, 7, 8, Fixed Days 1, 2, 14, 15, 28, 29, Early Termination and Last Visit.

• Incidence of ECG Evaluations of Potential Clinical Significance

  The measurement of ECG was one of the primary parameters to measure the safety and tolerability of individual participants. Incidence of TEAEs of potential clinical relevance include abnormal changes in heart rate and ECG intervals of PR, QRS, QT, QTcB, and QTcF that were identified based on pre-defined criteria.

  Titratrion Day 1 and 7, Fixed dose Day 1, 14, 28, Early Termination

• Incidence of Physical Examination Evaluation of Potential Clinical Significance

  The physical examination evaluation was one of the primary parameters to measure the safety and tolerability of individual participants. Incidence of TEAEs of potential clinical relevance include abnormal changes in the following body systems: head, ears, eyes, nose, and throat; thorax; abdomen; urogenital; extremities; neurological; and skin and mucosae.

  Physical examination was performed at Screening, check-in, and discharge

• Mean Change From Baseline to Study Completion in Simpson-Angus Scale (SAS) Total Score

  EPS was one of the primary parameters to measure the safety and tolerability of individual participants. The SAS is a rating scale used to measure EPS. The SAS scale consists of a list of 10 symptoms of parkinsonism (gait, arm dropping, shoulder shaking, elbow rigidity, wrist rigidity, head rotation, glabella tap, tremor, salivation, and akathisia), with each item rated from 0 to 4, with 0 being normal and 4 being the worst. The SAS Total score is sum of ratings for all 10 items, with possible Total scores from 0 to 40.

  End of Titration, Day 15, Day 29, Early Termination and Last visit

• Mean Change From Baseline to Study Completion in Barnes Akathisia Global Score

  EPS was one of the primary parameters to measure the safety and tolerability of individual participants. The Barnes Akathisia Rating Scale was an EPS rating scale. The Barnes Akathisia Rating Scale was used to assess the presence and severity of akathisia. This scale consists of 4 items. Only the 4th item, the Global Clinical Assessment of Akathisia, was evaluated in this trial. This item is rated on a 6 point scale, with 0 being best (absent) and 5 being worst (severe akathisia).

  End of Titration, Day 15, Day 29, Early Termination and Last visit

• Mean Change From Baseline to Study Completion in Abnormal Involuntary Movement Scale (AIMS) Rating Score.

  EPS was one of the primary parameters to measure the safety and tolerability of individual participants. The AIMS Scale was an EPS rating scale. The AIMS is a 12 item scale. The first 10 items are rated from 0 to 4 (0=best, 4=worst). Items 11 and 12, related to dental status, have dichotomous responses, 0=no and 1=yes. The AIMS Total Score is the sum of the ratings for the first seven items. The possible total scores are from 0 to 28.

  End of Titration, Day 15, Day 29, Early Termination and Last visit

• Change From Baseline to Study Completion in C-SSRS Score.

  The C-SSRS was one of the primary parameters to measure the safety and tolerability of individual participants. Suicidality was monitored during the trial using the C-SSRS. This scale consists of a baseline evaluation that assesses the lifetime experience of the participant with suicide events and suicidal ideation and a post-baseline evaluation that focuses on suicidality since the last trial visit.

  Baseline, End of Titration, Fixed dose Day 14 and 28, Day 15 and 29, Early Termination, Last Visit

Study Arms (4)

Cohort 1

EXPERIMENTAL

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

Cohort 2

EXPERIMENTAL

14 day titration phase and a 14 day fixed dose phase a daily dose of 3mg brexpiprazole/placebo.

Drug: Brexpiprazole

Cohort 3

EXPERIMENTAL

21 day titration phase and a 14 day fixed dose phase a daily dose of 3mg brexpiprazole/placebo.

Drug: Brexpiprazole

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

Brexpiprazole DRUG

up to 3mg oral dose once daily

Cohort 1; Cohort 2; Cohort 3

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 70 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Otsuka Pharmaceutical Development & Commercialization, Inc.: lead
• H. Lundbeck A/S: collaborator

Study Sites (4)

Accurate Clinical Trials

Kissimmee, Florida, United States

Location

Miami Jewish Health System

Miami, Florida, United States

Location

St. Louis Clinical Trials

St Louis, Missouri, United States

Location

CRI Lifetree- Philadelphia Research Center

Philadelphia, Pennsylvania, United States

Location

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

brexpiprazole

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Limitations and Caveats

Cohort 3 was not initiated based on the safety/tolerability results from Cohorts 1 and 2.

Results Point of Contact

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

800 562-3974

Study Officials

• James M. Youakim, MD

  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: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 7, 2012
• First Posted: August 22, 2012
• Study Start: July 1, 2012
• Primary Completion: May 1, 2013
• Study Completion: May 1, 2013
• Last Updated: February 4, 2016
• Results First Posted: February 4, 2016

Record last verified: 2016-01

Locations

US (4)