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

A Long-term, Phase 3, Multicenter, Open-label Trial to Evaluate the Safety and Tolerability of Oral OPC-34712 as Adjunctive Therapy in Adults With Major Depressive Disorder, the Orion Trial

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)

Study Overview

• Status: Completed
• Conditions: Mental Disorders; Depressive Disorder; Depression; Mood Disorders; Depressive Disorder, Major
• Intervention / Treatment: Drug: Escitalopram; Drug: OPC-34712; Drug: Fluoxetine; Drug: Paroxetine CR; Drug: Sertraline; Drug: Duloxetine; Drug: Venlafaxine XR

• Study Type: Interventional
• Enrollment (Actual): 2944
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Gatineau, Canada
    • Research Site
  • Penticton, Canada
    • Research Site
  • Pointe-Claire, Canada
    • Research Site
  • Sherbrooke, Canada
    • Research Site
  • Toronto, Canada
    • Research Site
• France
  • Arcachon, France
    • Research Site
  • Douai, France
    • Research Site
  • Elancourt, France
    • Research Site
  • Jarnac, France
    • Research Site
  • Orvault, France
    • Research Site
  • Palaiseau, France
    • Research Site
  • Toulouse, France
    • Research Site
• Germany
  • Achim, Germany
    • Research Site
  • Bochum, Germany
    • Research Site
  • Mittweida, Germany
    • Research Site
  • Stralsund, Germany
    • Research Site
  • Wurzburg, Germany
    • Research Site
• Hungary
  • Budapest, Hungary
    • Research Site
• Poland
  • Belchatow, Poland
    • Research Site
  • Bydgoszcz, Poland
    • Research Site
  • Katowice, Poland
    • Research Site
  • Kielce, Poland
    • Research Site
  • Lublin, Poland
    • Research Site
  • Poznań, Poland
    • Research Site
  • Pruszcz Gdanski, Poland
    • Research Site
  • Tuszyn, Poland
    • Research Site
  • Wroclaw, Poland
    • Research Site
  • Wrocław, Poland
    • Research Site
• Romania
  • Bucharest, Romania
    • Research Site
  • Iași, Romania
    • Research Site
  • Târgu-Mureş, Romania
    • Research Site
• Russian Federation
  • Arkhangelsk Region, Russian Federation
    • Research Site
  • Moscow, Russian Federation
    • Research Site
  • Roshchino, Russian Federation
    • Research Site
  • Rostov-na-Donu, Russian Federation
    • Research Site
  • Saint Petersberg, Russian Federation
    • Research Site
  • Saint Petersburg, Russian Federation
    • Research Site
  • Smolensk, Russian Federation
    • Research Site
  • St. Petersburg, Russian Federation
    • Research Site
  • Tonnel'nyy, Russian Federation
    • Research Site
• Serbia
  • Belgrade, Serbia
    • Research Site
  • Kragujevac, Serbia
    • Research Site
  • Nis, Serbia
    • Research Site
  • Novi Knezevac, Serbia
    • Research Site
• Slovakia
  • Bratislava, Slovakia
    • Research Site
  • Košice, Slovakia
    • Research Site
  • Michalovce, Slovakia
    • Research Site
• Ukraine
  • Chernihiv, Ukraine
    • Research Site
  • Kharkiv, Ukraine
    • Research Site
  • Kiev, Ukraine
    • Research Site
  • Poltava, Ukraine
    • Research Site
• United States
  • Alabama
    • Birmingham, Alabama, United States
      • Research Site
  • Arizona
    • Phoenix, Arizona, United States
      • Research Site
  • Arkansas
    • Little Rock, Arkansas, United States
      • Research Site
  • California
    • Beverly Hills, California, United States
      • Research Site
    • Costa Mesa, California, United States
      • Research Site
    • Glendale, California, United States
      • Research Site
    • Irvine, California, United States
      • Research Site
    • Oceanside, California, United States
      • Research Site
    • Redlands, California, United States
      • Research Site
    • San Diego, California, United States
      • Research Site
    • San Francisco, California, United States
      • Research Site
    • Santa Ana, California, United States
      • Research Site
    • Sherman Oaks, California, United States
      • Research Site
    • Temecula, California, United States
      • Research Site
    • Upland, California, United States
      • Research Site
  • Connecticut
    • Norwalk, Connecticut, United States
      • Research Site
  • Florida
    • Coral Gables, Florida, United States
      • Research Site
    • Coral Springs, Florida, United States
      • Research Site
    • Fort Myers, Florida, United States
      • Research Site
    • Gainesville, Florida, United States
      • Research Site
    • Hialeah, Florida, United States
      • Research Site
    • Jacksonville, Florida, United States
      • Research Site
    • Jacksonville Beach, Florida, United States
      • Research Site
    • Melbourne, Florida, United States
      • Research Site
    • Miami, Florida, United States
      • Research Site
    • Miami Springs, Florida, United States
      • Research Site
    • Oakland Park, Florida, United States
      • Research Site
    • Orlando, Florida, United States
      • Research Site
    • The Villages, Florida, United States
      • Research Site
    • Winter Park, Florida, United States
      • Research Site
  • Georgia
    • Alpharetta, Georgia, United States
      • Research Site
    • Atlanta, Georgia, United States
      • Research Site
    • Decatur, Georgia, United States
      • Research Site
    • Smyrna, Georgia, United States
      • Research Site
  • Illinois
    • Oak Brook, Illinois, United States
      • Research Site
  • Indiana
    • Indianapolis, Indiana, United States
      • Research Site
    • Lafayette, Indiana, United States
      • Research Site
  • Kansas
    • Prairie Village, Kansas, United States
      • Research Site
    • Wichita, Kansas, United States
      • Research Site
  • Louisiana
    • Lake Charles, Louisiana, United States
      • Research Site
    • New Orleans, Louisiana, United States
      • Research Site
    • Shreveport, Louisiana, United States
      • Research Site
  • Maryland
    • Baltimore, Maryland, United States
      • Research Site
  • Massachusetts
    • Belmont, Massachusetts, United States
      • Research Site
    • Boston, Massachusetts, United States
      • Research Site
    • Methuen, Massachusetts, United States
      • Research Site
    • Watertown, Massachusetts, United States
      • Research Site
    • Weymouth, Massachusetts, United States
      • Research Site
  • Michigan
    • Rochester Hills, Michigan, United States
      • Research Site
  • Missouri
    • Creve Coeur, Missouri, United States
      • Research Site
  • Nevada
    • Las Vegas, Nevada, United States
      • Research Site
  • New Jersey
    • Cherry Hill, New Jersey, United States
      • Research Site
    • Tom River, New Jersey, United States
      • Research Site
  • New York
    • Brooklyn, New York, United States
      • Research Site
    • Jamaica, New York, United States
      • Research Site
    • New York, New York, United States
      • Research Site
    • Rochester, New York, United States
      • Research Site
    • Staten Island, New York, United States
      • Research Site
  • North Carolina
    • Raleigh, North Carolina, United States
      • Research Site
    • Wilmington, North Carolina, United States
      • Research Site
  • Ohio
    • Beachwood, Ohio, United States
      • Research Site
    • Cincinnati, Ohio, United States
      • Research Site
    • Columbus, Ohio, United States
      • Research Site
    • Dayton, Ohio, United States
      • Research Site
    • Toledo, Ohio, United States
      • Research Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States
      • Research Site
  • Oregon
    • Portland, Oregon, United States
      • Research Site
    • Salem, Oregon, United States
      • Research Site
  • Pennsylvania
    • Allentown, Pennsylvania, United States
      • Research Site
    • Bala-Cynwyd, Pennsylvania, United States
      • Research Site
    • Bridgeville, Pennsylvania, United States
      • Research Site
    • Norristown, Pennsylvania, United States
      • Research Site
    • Philadelphia, Pennsylvania, United States
      • Research Site
  • Rhode Island
    • Lincoln, Rhode Island, United States
      • Research Site
  • South Carolina
    • Columbia, South Carolina, United States
      • Research Site
  • Tennessee
    • Memphis, Tennessee, United States
      • Research Site
  • Texas
    • Arlington, Texas, United States
      • Research Site
    • Austin, Texas, United States
      • Research Site
    • Dallas, Texas, United States
      • Research Site
    • Houston, Texas, United States
      • Research Site
    • San Antonio, Texas, United States
      • Research Site
    • Wichita Falls, Texas, United States
      • Research Site
  • Utah
    • Murray, Utah, United States
      • Research Site
  • Vermont
    • Woodstock, Vermont, United States
      • Research Site
  • Virginia
    • Charlottesville, Virginia, United States
      • Research Site
    • Herndon, Virginia, United States
      • Research Site
    • Richmond, Virginia, United States
      • Research Site
  • Washington
    • Bellevue, Washington, United States
      • Research Site
    • Kirkland, Washington, United States
      • Research Site
    • Seattle, Washington, United States
      • Research Site
    • Spokane, Washington, United States
      • Research Site
  • Wisconsin
    • Brown Deer, Wisconsin, United States
      • Research Site
    • Middleton, Wisconsin, United States
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: OPC-34712 (Brexpiprazole) and Escitalopram; OPC-34712: Oral tablet; 0.5 to 3 mg/day Escitalopram: Oral tablet; 10 or 20 mg/day	Drug: Escitalopram; Tablet; Other Names: Lexapro; Drug: OPC-34712; Tablet
Experimental: OPC-34712 and Fluoxetine; OPC-34712: Oral tablet; 0.5 to 3 mg/day Fluoxetine: Oral capsules; 20 or 40 mg/day	Drug: OPC-34712; Tablet; Drug: Fluoxetine; Capsule; Other Names: Prozac
Experimental: OPC-34712 and Paroxetine CR; OPC-34712: Oral tablet; 0.5 to 3 mg/day Paroxetine CR: Oral controlled-release tablets; 37.5 or 50 mg/day	Drug: OPC-34712; Tablet; Drug: Paroxetine CR; Controlled-release tablets; Other Names: Paxil CR
Experimental: OPC-34712 and Sertraline; OPC-34712: Oral tablet; 0.5 to 3 mg/day Sertraline: Oral tablets; 100, 150, or 200 mg/day	Drug: OPC-34712; Tablet; Drug: Sertraline; Tablets; Other Names: Zoloft
Experimental: OPC-34712 and Duloxetine; OPC-34712: Oral tablet; 0.5 to 3 mg/day Duloxetine: Oral delayed-release capsules; 40 or 60 mg/day	Drug: OPC-34712; Tablet; Drug: Duloxetine; Delayed-release capsules; Other Names: Cymbalta
Experimental: OPC-34712 and Venlafaxine XR; OPC-34712: Oral tablet; 0.5 to 3 mg/day Venlafaxine XR: Oral extended-release capsules; 75, 150, or 225 mg/day	Drug: OPC-34712; Tablet; Drug: Venlafaxine XR; Extended-release capsules; Other Names: Effexor XR

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline in Clinical Global Impression - Severity (CGI-S) of Illness Score	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.	From screening to week 52/early termination
Change From Baseline in Mean Clinical Global Impression - Improvement (CGI-I) Score	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.	From screening to week 52/early termination
Summary of Mean Change From Baseline in Sheehan Disability Scale (SDS) Mean Score	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.	From screening to week 52/early termination
Change From Baseline in the Inventory of Depressive Symptomatology - Self Report (IDS-SR) Total Score	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.	From screening to week 52/early termination

Collaborators and Investigators

• Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.

Publications and helpful links

General Publications

• Newcomer JW, Eriksson H, Zhang P, Meehan SR, Weiss C. Changes in Metabolic Parameters and Body Weight in Patients With Major Depressive Disorder Treated With Adjunctive Brexpiprazole: Pooled Analysis of Phase 3 Clinical Studies. J Clin Psychiatry. 2019 Oct 1;80(6):18m12680. doi: 10.4088/JCP.18m12680.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2011
• Primary Completion (Actual): April 18, 2017
• Study Completion (Actual): May 18, 2017

Study Registration Dates

• First Submitted: May 24, 2011
• First Submitted That Met QC Criteria: May 25, 2011
• First Posted (Estimate): May 26, 2011

Study Record Updates

• Last Update Posted (Actual): September 17, 2018
• Last Update Submitted That Met QC Criteria: September 14, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: Major Depressive Disorder; OPC-34712; brexpiprazole; Adjunctive Treatment
• Additional Relevant MeSH Terms: Behavioral Symptoms; Pathologic Processes; Depression; Depressive Disorder; Disease; Mental Disorders; Mood Disorders; Depressive Disorder, Major; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Dopamine Agents; Cytochrome P-450 Enzyme Inhibitors; Antidepressive Agents, Second-Generation; Serotonin and Noradrenaline Reuptake Inhibitors; Cytochrome P-450 CYP2D6 Inhibitors; Sertraline; Duloxetine Hydrochloride; Citalopram; Paroxetine; Venlafaxine Hydrochloride; Fluoxetine
• Other Study ID Numbers: 331-10-238

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No