Safety and Tolerability of Oral OPC-34712 as Adjunctive Therapy in Adults With Major Depressive Disorder (the Orion Trial)

Phase 3

Completed

Conditions: Depression
Depressive Disorder, Major
Depressive Disorder
Mood Disorders
Mental Disorders

Interventions: Drug: OPC-34712
Drug: Venlafaxine XR
Drug: Sertraline
Drug: Fluoxetine
Drug: Paroxetine CR
Drug: Escitalopram
Drug: Duloxetine

Registration Number: NCT01360866

Lead Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.

Brief Summary: To assess the long-term safety and tolerability of oral OPC-34712 (brexpiprazole), given in addition to an FDA approved antidepressant (ADT) for the treatment of adults with Major Depressive Disorder (MDD)

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 2944

Inclusion Criteria

Male and Female outpatients 18-65 years of age

Eligible subjects from Trials 331-10-227, 331-10-228 or 331-12-282:

Subjects who completed participation in the Double-blind Randomization Phase (i.e. Week 14 visit) in Trial 331-10-227, Trial 331-10-228, or Trial 331-12-282 or
Subjects who met criteria for a response, but did not meet criteria for remission at Week 14 of either trial

Eligible subjects from other Phase 3, Double-blind, Brexpiprazole MDD trials:

• Subjects who completed the last scheduled visit of the prior Double-blind Randomized Phase 3 trial.

Exclusion Criteria

Females who are breast-feeding and/or who have a positive pregnancy test result prior to receiving OPC-34712.
Subjects with a major protocol violation during the course of their participation in the Double-blind Randomization Phase

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
OPC-34712 and Venlafaxine XR	Venlafaxine XR	OPC-34712: Oral tablet; 0.5 to 3 mg/day Venlafaxine XR: Oral extended-release capsules; 75, 150, or 225 mg/day
OPC-34712 (Brexpiprazole) and Escitalopram	OPC-34712	OPC-34712: Oral tablet; 0.5 to 3 mg/day Escitalopram: Oral tablet; 10 or 20 mg/day
OPC-34712 and Sertraline	Sertraline	OPC-34712: Oral tablet; 0.5 to 3 mg/day Sertraline: Oral tablets; 100, 150, or 200 mg/day
OPC-34712 and Venlafaxine XR	OPC-34712	OPC-34712: Oral tablet; 0.5 to 3 mg/day Venlafaxine XR: Oral extended-release capsules; 75, 150, or 225 mg/day
OPC-34712 and Fluoxetine	Fluoxetine	OPC-34712: Oral tablet; 0.5 to 3 mg/day Fluoxetine: Oral capsules; 20 or 40 mg/day
OPC-34712 and Sertraline	OPC-34712	OPC-34712: Oral tablet; 0.5 to 3 mg/day Sertraline: Oral tablets; 100, 150, or 200 mg/day
OPC-34712 and Fluoxetine	OPC-34712	OPC-34712: Oral tablet; 0.5 to 3 mg/day Fluoxetine: Oral capsules; 20 or 40 mg/day
OPC-34712 and Paroxetine CR	OPC-34712	OPC-34712: Oral tablet; 0.5 to 3 mg/day Paroxetine CR: Oral controlled-release tablets; 37.5 or 50 mg/day
OPC-34712 and Duloxetine	OPC-34712	OPC-34712: Oral tablet; 0.5 to 3 mg/day Duloxetine: Oral delayed-release capsules; 40 or 60 mg/day
OPC-34712 and Paroxetine CR	Paroxetine CR	OPC-34712: Oral tablet; 0.5 to 3 mg/day Paroxetine CR: Oral controlled-release tablets; 37.5 or 50 mg/day
OPC-34712 (Brexpiprazole) and Escitalopram	Escitalopram	OPC-34712: Oral tablet; 0.5 to 3 mg/day Escitalopram: Oral tablet; 10 or 20 mg/day
OPC-34712 and Duloxetine	Duloxetine	OPC-34712: Oral tablet; 0.5 to 3 mg/day Duloxetine: Oral delayed-release capsules; 40 or 60 mg/day

Primary Outcome Measures

Name	Time	Method
Adverse Events (AEs) - All Participants	From screening to week 52/early termination	To assess the frequency and severity of AEs as the variables of safety and tolerability of brexpiprazole.

Secondary Outcome Measures

Name	Time	Method
Summary of Mean Change From Baseline in Sheehan Disability Scale (SDS) Mean Score	From screening to week 52/early termination	The SDS was a self-rated instrument used to measure the effect of the participant's symptoms on regular life responsibilities. The SDS was a visual analogue scale that used spatio-visual, numeric, and verbal descriptive anchors simultaneously to assess disability across the 3 domains with scores from 0 = not at all, to 10 = extremely. Scores of 5 and above were associated with significant functional impairment.
Mean Change From Baseline in Clinical Global Impression - Severity (CGI-S) of Illness Score	From screening to week 52/early termination	The severity of illness for each participant was rated using the CGI-S . On the basis of the investigator answer to the question: "Considering your total clinical experience with this particular population, how mentally ill was the participant at that time?" Response choices included: 0 = not assessed; 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill participants.
Change From Baseline in Mean Clinical Global Impression - Improvement (CGI-I) Score	From screening to week 52/early termination	The efficacy of trial treatment was rated for each participant using the CGI-I. The investigator rated the participant's total improvement whether or not it was due entirely to drug treatment. All responses were compared to the participant's condition at screening. Response choices included: 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse and 7 = very much worse.
Change From Baseline in the Inventory of Depressive Symptomatology - Self Report (IDS-SR) Total Score	From screening to week 52/early termination	The IDS-SR was a 30-item self-report measure used to assess core diagnostic depressive symptoms as well as atypical and melancholic symptom features of MDD. The IDS-SR consists of 30 items, all rated on a 0 to 3 scale with 0 being the "best" rating and 3 being the "worst" rating. The IDS-SR Total Score is the sum of ratings of 28 item scores. The possible IDS-SR Total Score ranges from 0 (best) to 84 (worst). Under item 9, two sub-items 9A and 9B exist, with possible scores of 1, 2 or 3 for item 9A, and 0 or 1 for item 9B. The scores for these two sub-items are not included in the calculation of the total score. Item 11 or item 12 should be completed but not both, and similarly, item 13 or item 14 should be completed but not both. If the number of items recorded is at least 23 and at most 27, the IDS-SR Total Score will be the mean of the recorded items multiplied by 28 and then rounded to the first decimal place.