A Double-Blind, Placebo-Controlled Study of Aripiprazole Adjunctive to Antidepressant Therapy

NCT00683852 | Completed Phase 3 Results

• 1 other identifier: BMS - 2008A053242
• Study Type: interventional
• Target: 225
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine whether a reduced dose of aripiprazole is effective in treating patients with major depressive disorder

Conditions

Major Depressive Disorder

Keywords

Depression

Outcome Measures

Primary Outcomes (1)

• MADRS (Montgomery-Asberg Depression Rating Scale) Response Rate

  The primary outcome was the difference in response rate (decrease in MADRS total score of at least 50%) using the SPCD (sequential parallel comparison design). The 10-item Montgomery-Asberg Depression Rating Scale (MADRS), which measures depression severity over the past week, was completed by clinicians using an MGH structured interview. Each item is measured on a scale from 0 to 6, and the items are summed to find the total score. The total minimum score is 0 units on a scale and the total maximum score is 60 units on a scale, where higher scores indicate more severe depression.

  12 weeks

Secondary Outcomes (4)

• MADRS (Montgomery-Asberg Depression Rating Scale) Readmission Rate

  12 weeks

• Mean Change in MADRS (Montgomery-Asberg Depression Rating Scale) Score From Baseline to the End of Follow-up

  Baseline and 12 Weeks

• Mean Change in Clinical Global Impression of Severity (CGI-S)

  Baseline and 12 weeks

• Mean Change in Symptom Questionnaire (SQ)

  Baseline and 12 weeks

Other Outcomes (3)

• Treatment Emergent AEs in Two Treatment Groups - Safety Sample

  12 Weeks

• Number of Patients With Treatment Emergent AEs in Two Treatment Groups - Placebo Non-Responders

  12 Weeks

• Number of Patients With Treatment Emergent AEs in Two Treatment Groups - People Exclusively on Drug or Placebo Throughout the Study

  12 Weeks

Study Arms (3)

Drug 2mg/Drug 5mg

ACTIVE COMPARATOR

patients randomly assigned to the drug/drug sequence, the dose of aripiprazole will be 2 mg/day during the first phase of the study, and 5 mg/day in the second phase.

Drug: Aripiprazole 5mg; Drug: Aripiprazole 2mg

Placebo/Drug 2mg

ACTIVE COMPARATOR

For patients randomly assigned to the placebo/drug sequence, the dose of aripiprazole will be 2 mg/day during the second phase of the study.

Drug: Aripiprazole 2mg; Drug: Placebo

Placebo/Placebo

PLACEBO COMPARATOR

for patients randomly assigned to the placebo/placebo sequence, study medication will be placebo during both phases of the study.

Drug: Placebo

Interventions

Aripiprazole 5mg DRUG

Tablet dose of aripiprazole will be 2 mg/day during the first phase (30 days) of the study, and 5 mg/day in the second phase (30 days)

Also known as: Abilify

Drug 2mg/Drug 5mg

Aripiprazole 2mg DRUG

For patients randomly assigned to the placebo/drug sequence, the dose of aripiprazole will be 2 mg/day during the second phase of the study (30 days)

Also known as: Abilify

Drug 2mg/Drug 5mg; Placebo/Drug 2mg

Placebo DRUG

for patients randomly assigned to the placebo/placebo sequence, study medication will be placebo during both phases of the study (60 days)

Placebo/Drug 2mg; Placebo/Placebo

Eligibility Criteria

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

You may qualify if:

• Patients able to give informed consent, and/or consent obtained from a legally acceptable representative (as required by IRB/IEC), prior to the initiation of any protocol required procedures.
• Patients must be able to understand the nature of the study, agree to comply with the prescribed dosage regimens, report for regularly scheduled office visits, and communicate to study personnel about adverse events and concomitant medication use.
• Patients with a diagnosis of major depressive episode as defined by DSM-IV-TR criteria, based on the SCID-I/P; their major depressive episode must be deemed "valid" using the SAFER criteria interview administered by remote, independent raters.
• Patients who have reported a history for the current depressive episode of an inadequate response to at least one and no more than three adequate antidepressant treatments. An inadequate response is defined as less than a 50% reduction in depressive symptom severity, as assessed by the MGH ATRQ administered by remote, independent raters. An adequate trial is defined as an antidepressant treatment for at least 6 weeks duration at least at a minimum dose as specified in the MGH ATRQ.
• Patients must be able to be reliably rated on the psychiatric scales required by the protocol.
• Men and women, ages 18 to 65 Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 4 weeks after the last dose of investigational product in such a manner that the risk of pregnancy is minimized.
• WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal (defined as amenorrhea ³ 12 consecutive months; or women on hormone replacement therapy \[HRT\] with documented serum follicle stimulating hormone \[FSH\] level \> 35 mIU/mL). Even women who are using oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or are practicing abstinence or where their partner is sterile (e.g., vasectomy) should be considered to be of childbearing potential.
• WOCBP must have a negative urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to the start of investigational product.
• Meet DSM-IV criteria (by Structured Clinical Interview for DSM-IV - SCID-I/P) for MDD, current;
• Quick Inventory of Depressive Symptomatology - Self-Rated (QIDS-SR) (22) score of at least 16 at both screen and baseline visits;
• Treated with an SSRI at adequate doses (defined as 20mg/day or more of fluoxetine, citalopram; paroxetine 30mg/day or more or 37.5 mg/day or more of paroxetine CR; 10 mg/day or more of escitalopram, 50mg/day or more of sertraline, and 150 mg/day or more of venlafaxine) during the current episode for at least 8 weeks, with the same, adequate dose over the last 4 weeks;
• Between the screen and baseline visit, patients must be documented prospectively to have received a stable dose of their SSRI or venlafaxine for at least 2 weeks.
• Additional criteria for defining response and non-response for patients in Phase 2 eligible for the pooling of the data with all the patients in Phase 1. Among patients pre-randomized to receive placebo in both phases or to receive placebo in Phase 1 and aripiprazole in phase 2, only those meeting non-response criteria will be added to the primary efficacy sample:
• Placebo non-responders are defined as those patients who failed to achieve a 50% decrease in their MADRS score at visit 3,
• Have a MADRS score of \> 16 at visit 3

You may not qualify if:

• WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period \[and for up to 4 weeks after the last dose of investigational product\].
• WOCBP using a prohibited contraceptive method.
• Women who are pregnant or breastfeeding.
• Women with a positive pregnancy test on enrollment or prior to investigational product administration.
• Sexually active fertile men not using effective birth control if their partners are WOCBP.
• Patients who report an inadequate response (less than 50% decrease in depressive symptom severity) to more than two adequate trials of antidepressant treatments during the current depressive episode (including monotherapy treatment and distinct combination regimens) at a therapeutic dose (as defined by the ATRQ) and for an adequate duration (minimum six weeks for any monotherapy).
• Patients who report treatment with adjunctive antipsychotic medication with an antidepressant for a minimum of two weeks during the current depressive episode.
• Patients with a current need for involuntary commitment or who have been hospitalized within four weeks of the Screening Visit for the current major depressive episode.
• Patients who have received ECT during the current episode.
• Patients who have a current Axis I diagnosis of:
• Delirium, dementia, amnestic, or other cognitive disorder;
• Schizophrenia or other psychotic disorder, based on the SCID-I/P;
• Bipolar I or II disorder, based on the SCID-I/P;
• Patients with a clinically significant Axis II (DSM-IV-TR) diagnosis of borderline, antisocial, paranoid, schizoid, schizotypal or histrionic personality disorder.
• Patients experiencing hallucinations, delusions, or any psychotic symptomatology in the current depressive episode.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (4)

• Marcus RN, McQuade RD, Carson WH, Hennicken D, Fava M, Simon JS, Trivedi MH, Thase ME, Berman RM. The efficacy and safety of aripiprazole as adjunctive therapy in major depressive disorder: a second multicenter, randomized, double-blind, placebo-controlled study. J Clin Psychopharmacol. 2008 Apr;28(2):156-65. doi: 10.1097/JCP.0b013e31816774f9.

  PMID: 18344725 BACKGROUND

• Berman RM, Marcus RN, Swanink R, McQuade RD, Carson WH, Corey-Lisle PK, Khan A. The efficacy and safety of aripiprazole as adjunctive therapy in major depressive disorder: a multicenter, randomized, double-blind, placebo-controlled study. J Clin Psychiatry. 2007 Jun;68(6):843-53. doi: 10.4088/jcp.v68n0604.

  PMID: 17592907 BACKGROUND

• Fava M, Mischoulon D, Iosifescu D, Witte J, Pencina M, Flynn M, Harper L, Levy M, Rickels K, Pollack M. A double-blind, placebo-controlled study of aripiprazole adjunctive to antidepressant therapy among depressed outpatients with inadequate response to prior antidepressant therapy (ADAPT-A Study). Psychother Psychosom. 2012;81(2):87-97. doi: 10.1159/000332050. Epub 2012 Jan 25.

  PMID: 22286203 RESULT

• Mischoulon D, Witte J, Levy M, Papakostas GI, Pet LR, Hsieh WH, Pencina MJ, Ward S, Pollack MH, Fava M. Efficacy of dose increase among nonresponders to low-dose aripiprazole augmentation in patients with inadequate response to antidepressant treatment: a randomized, double-blind, placebo-controlled, efficacy trial. J Clin Psychiatry. 2012 Mar;73(3):353-7. doi: 10.4088/JCP.10m06541. Epub 2011 Sep 20.

  PMID: 21939613 DERIVED

Related Links

• A double-blind, placebo-controlled study of aripiprazole adjunctive to antidepressant therapy among depressed outpatients with inadequate response to prior antidepressant therapy (ADAPT-A Study)

MeSH Terms

Conditions

Depressive Disorder, Major; Depression

Interventions

Aripiprazole

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Martina Flynn, Director, Clinical Trial Operations
• Organization: Massachusetts General Hospital, CTNI

mflynn2@partners.org

617-643-6028

Study Officials

• Maurizio Fava, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Executive Vice Chair, Department of Psychiatry; Executive Director, Clinical Trials Network and Institute (CTNI); Director, Depression Clinical and Research Program (DCRP)

Study Record Dates

• First Submitted: May 22, 2008
• First Posted: May 26, 2008
• Study Start: September 1, 2008
• Primary Completion: September 1, 2009
• Study Completion: September 1, 2009
• Last Updated: July 19, 2017
• Results First Posted: July 19, 2017

Record last verified: 2017-06

Locations

US (1)