Safety and Efficacy of Cariprazine as an Adjunctive to Antidepressant Therapy in Major Depressive Disorder

NCT01469377 | Completed Phase 2 Results

• 1 other identifier: RGH-MD-75
• Study Type: interventional
• Target: 819
• Locations: 6 countries
• Sites: 72

Brief Summary

An outpatient study to evaluate the safety and efficacy of cariprazine as adjunct to antidepressant therapy (ADT) in participants with major depressive disorder (MDD) who have an inadequate response to ADT alone. This clinical study compared cariprazine + ADT with placebo + ADT in outpatients with a diagnosis of MDD and an inadequate response to ADT. The study consisted of approximately 2 weeks of screening and washout followed by 8 weeks of double-blind treatment followed by a 1 week safety follow-up.

Conditions

Major Depressive Disorder

Keywords

Major depressive disorder; Depression

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at Week 8

  The MADRS is a clinician-rated scale to assess depressive symptomatology during the preceding week. Participants are rated on 10 items (feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty concentrating, and lack of interest) each on a 7-point scale from 0 (no symptoms) to 6 (symptoms of maximum severity). The total score ranges from 0 to 60 with a higher score indicating more depression. A negative change score indicates improvement.

  Baseline to Week 8

Secondary Outcomes (1)

• Change From Baseline in the Sheehan Disability Scale (SDS) Total Score at Week 8

  Baseline to Week 8

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Participants received placebo orally once a day for 8 weeks. Each participant continued to take the same dose of antidepressant therapy (bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, sertraline, venlafaxine, or vilazodone) the participant was receiving prior to entering this study throughout treatment.

Drug: Placebo

Cariprazine 1-2 mg

EXPERIMENTAL

Participants received cariprazine orally once a day for 8 weeks. Participants received cariprazine 0.5 mg on Days 1 and 2 and 1.0 mg on Days 3-7. At the investigator's discretion dose levels could be increased during Week 2. Dose levels allowed during Week 2 were 1.0 or 1.5 mg. A second dose increase was allowed starting at Week 3. Dose levels allowed during Week 3 and the remainder of the treatment period were 1.0, 1.5, or 2.0 mg. Each participant continued to take the same dose of antidepressant therapy (bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, sertraline, venlafaxine, or vilazodone) the participant was receiving prior to entering this study throughout treatment.

Drug: Cariprazine

Cariprazine 2-4.5 mg

EXPERIMENTAL

Participants received cariprazine orally once a day for 8 weeks. Participants received cariprazine 0.5 mg on Days 1 and 2, 1.0 mg on Day 3, 1.5 mg on Day 4, and 2.0 mg on Days 5-7. At the investigator's discretion dose levels could be increased during Week 2. Dose levels allowed during Week 2 were 2.0 or 3.0 mg. A second dose increase was allowed starting at Week 3. Dose levels allowed during Week 3 and the remainder of the treatment period were 2.0, 3.0, or 4.5 mg. Each participant continued to take the same dose of antidepressant therapy (bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, sertraline, venlafaxine, or vilazodone) the participant was receiving prior to entering this study throughout treatment.

Drug: Cariprazine

Interventions

Placebo DRUG

Placebo was supplied in capsules

Placebo

Cariprazine DRUG

Cariprazine was supplied in capsules.

Cariprazine 1-2 mg; Cariprazine 2-4.5 mg

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female outpatients 18 to 65 years of age, inclusive.
• Currently meet the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria for moderate to severe major depressive disorder (MDD).
• Current major depressive episode of at least 8 weeks and not exceeding 24 months in duration.
• Ongoing inadequate response to protocol allowed antidepressant therapy (ADT).

You may not qualify if:

• Principal DSM-IV-TR-based diagnosis of an axis I disorder, other than MDD,
• Women who are pregnant, or planning to become pregnant or breastfeed during the study or not practicing reliable contraception that will continue through out the study.
• History of meeting DSM-IV-TR criteria for:
• Depressive episode with psychotic or catatonic features.
• Manic, hypomanic or mixed episode, including bipolar disorder and substance induced manic, hypomanic or mixed episode.
• Schizophrenia, schizoaffective, or other psychotic disorder.
• Obsessive-compulsive disorder.
• Bulimia or anorexia nervosa.
• Dementia, amnesic, or other cognitive disorder.
• Mental retardation.
• Participants considered a suicide risk.

Sponsors & Collaborators

• Forest Laboratories: lead
• Gedeon Richter Ltd.: collaborator

Study Sites (72)

Forest Investigative Site 077

Garden Grove, California, 92845, United States

Location

Forest Investigative Site 019

National City, California, 91950, United States

Location

Forest Investigative Site 039

Oceanside, California, 92056, United States

Location

Forest Investigative Site 015

Orange, California, 92868, United States

Location

Forest Investigative Site 050

Orange, California, 92868, United States

Location

Forest Investigative Site 008

Redlands, California, 92374, United States

Location

Forest Investigative Site 066

Sherman Oaks, California, 91403, United States

Location

Forest Investigative Site 063

Gainesville, Florida, 32607, United States

Location

Forest Investigative Site 029

Jacksonville, Florida, 32256, United States

Location

Forest Investigative Site 012

Kissimmee, Florida, 34741, United States

Location

Forest Investigative Site 023

Miami, Florida, 33183, United States

Location

Forest Investigative Site 026

Orlando, Florida, 32806, United States

Location

Forest Investigative Site 062

Atlanta, Georgia, 30328, United States

Location

Forest Investigative Site 065

Smyrna, Georgia, 30080, United States

Location

Forest Investigative Site 074

Prairie Village, Kansas, 66206, United States

Location

Forest Investigative Site 040

Flowood, Mississippi, 39232, United States

Location

Forest Investigative Site 068

Creve Coeur, Missouri, 63141, United States

Location

Forest Investigative Site 061

Cherry Hill, New Jersey, 08002, United States

Location

Forest Investigative Site 038

Marlton, New Jersey, 08053, United States

Location

Forest Investigative Site 030

Albuquerque, New Mexico, 87106, United States

Location

Forest Investigative Site 076

Brooklyn, New York, 11235, United States

Location

Forest Investigative Site 037

Mount Kisco, New York, 10549, United States

Location

Forest Investigative Site 067

New York, New York, 10021, United States

Location

Forest Investigative Site 049

New York, New York, 10168, United States

Location

Forest Investigative Site 047

Canton, Ohio, 44718, United States

Location

Forest Investigative Site 021

Dayton, Ohio, 45417, United States

Location

Forest Investigative Site 022

Portland, Oregon, 97210, United States

Location

Forest Investigative Site 027

Salem, Oregon, 97301, United States

Location

Forest Investigative Site 069

Bridgeville, Pennsylvania, 15017, United States

Location

Forest Investigative Site 025

Philadelphia, Pennsylvania, 19139, United States

Location

Forest Investigative Site 031

Reading, Pennsylvania, 19604, United States

Location

Forest Investigative Site 048

Memphis, Tennessee, 38119, United States

Location

Forest Investigative Site 024

Austin, Texas, 78731, United States

Location

Forest Investigative Site 020

Dallas, Texas, 75231, United States

Location

Forest Investigative Site 070

Houston, Texas, 77054, United States

Location

Forest Investigative Site 080

San Antonio, Texas, 78229, United States

Location

Forest Investigative Site 028

Salt Lake City, Utah, 84106, United States

Location

Forest Investigative Site 032

Bellevue, Washington, 98007, United States

Location

Forest Investigative Site 034

Kirkland, Washington, 98033, United States

Location

Forest Investigative Site 203

Tallinn, 10614, Estonia

Location

Forest Investigative Site 201

Tallinn, 10617, Estonia

Location

Forest Investigative Site 206

Tallinn, 11615, Estonia

Location

Forest Investigative Site 205

Tallinn, 13517, Estonia

Location

Forest Investigative Site 204

Tartu, 50406, Estonia

Location

Forest Investigative Site 208

Tartu, 50417, Estonia

Location

Forest Investigative Site 207

Tartu, 51014, Estonia

Location

Forest Investigative Site 202

Võru, 65608, Estonia

Location

Forest Investigative Site 301

Helsinki, 100, Finland

Location

Forest Investigative Site 302

Helsinki, 100, Finland

Location

Forest Investigative Site 304

Helsinki, 100, Finland

Location

Forest Investigative Site 303

Helsinki, 40100, Finland

Location

Forest Investigative Site 305

Kuopio, 70110, Finland

Location

Forest Investigative Site 308

Oulu, 90100, Finland

Location

Forest Investigative Site 307

Pori, 28100, Finland

Location

Forest Investigative Site 602

Banská Štiavnica, 96901, Slovakia

Location

Forest Investigative Site 603

Bardejov, 08501, Slovakia

Location

Forest Investigative Site 604

Bratislava, 82007, Slovakia

Location

Forest Investigative Site 606

Bratislava, 85101, Slovakia

Location

Forest Investigative Site 601

Michalovce, 7101, Slovakia

Location

Forest Investigative Site 605

Rimavská Sobota, 97901, Slovakia

Location

Forest Investigative Site 607

Rimavská Sobota, 97912, Slovakia

Location

Forest Investigative Site 803

Lund, 22222, Sweden

Location

Forest Investigative Site 802

Malmo, 21152, Sweden

Location

Forest Investigative Site 801

Stockholm, 17145, Sweden

Location

Forest Investigative Site 705

Stepanivka, Kherson Oblast, 73488, Ukraine

Location

Forest Investigative Site 703

Kharkiv, 61068, Ukraine

Location

Forest Investigative Site 704

Kharkiv, 61068, Ukraine

Location

Forest Investigative Site 702

Kyiv, 02660, Ukraine

Location

Forest Investigative Site 701

Kyiv, 04080, Ukraine

Location

Forest Investigative Site 710

Luhansk, 91045, Ukraine

Location

Forest Investigative Site 709

Odesa, 65014, Ukraine

Location

Forest Investigative Site 706

Vinnytsia, 21005, Ukraine

Location

Related Publications (1)

• Durgam S, Earley W, Guo H, Li D, Nemeth G, Laszlovszky I, Fava M, Montgomery SA. Efficacy and safety of adjunctive cariprazine in inadequate responders to antidepressants: a randomized, double-blind, placebo-controlled study in adult patients with major depressive disorder. J Clin Psychiatry. 2016 Mar;77(3):371-8. doi: 10.4088/JCP.15m10070.

  PMID: 27046309 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Major; Depression

Interventions

cariprazine

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Results Point of Contact

• Title: Therapeutic Area Head
• Organization: Allergan

clinicaltrials@allergan.com

714-246-4500

Study Officials

• Willie Earley, MD

  Allergan

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 8, 2011
• First Posted: November 10, 2011
• Study Start: December 15, 2011
• Primary Completion: December 12, 2013
• Study Completion: December 12, 2013
• Last Updated: May 1, 2018
• Results First Posted: May 1, 2018

Record last verified: 2018-03

Locations

SL (7); UA (8); FI (7); US (39); ES (8); SE (3)