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

Otsuka

Status and phase

Completed

Phase 1

Conditions

Major Depressive Disorder

Treatments

Drug: Placebo

Drug: Brexpiprazole

Study type

Interventional

Funder types

Industry

Identifiers

NCT01670279

331-12-291

Details and patient eligibility

About

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.

Full 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).

Enrollment

18 patients

Sex

All

Ages

70 to 85 years old

Volunteers

No Healthy Volunteers

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.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Double Blind

18 participants in 4 patient groups, including a placebo group

Cohort 1

Experimental group

Description:

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.

Treatment:

Drug: Brexpiprazole

Cohort 2

Experimental group

Description:

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

Treatment:

Drug: Brexpiprazole

Cohort 3

Experimental group

Description:

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