Antidepressant Plus Asenapine Versus Antidepressant Plus Placebo for Depression

A Randomized, Blinded, Comparison of Asenapine and Placebo as Adjunctive Treatment in Patients With Non-Psychotic Major Depressive Disorder Incompletely Responsive to Antidepressant Monotherapy

This is a 6-week comparison of asenapine versus placebo as an add-on to ongoing antidepressant treatment in patients with major depression who have not had a complete therapeutic response to treatment with the antidepressant alone.

The investigators hypothesize that added asenapine will produce greater reductions in depression than will added placebo.

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder Without Psychotic Features
• Intervention / Treatment: Drug: Asenapine 5-20 mg daily; Drug: Placebo 1-4 tablets daily

Detailed Description

The investigators will undertake a 6-week, double-blind, randomized, parallel-group, placebo-controlled trial of adjunctive asenapine in 130 patients with MDD without psychosis who have had an incomplete therapeutic response to treatment with an antidepressant medication alone.

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Georgia Health Sciences University
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Durham, North Carolina, United States, 27704
      • Carolina Behavioral Care
    • Greenville, North Carolina, United States, 27834
      • Brody School of Medicine at East Carolina University
    • Raleigh, North Carolina, United States, 27603
      • North Carolina Psychiatric Research Center

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:

-130 male or female patients, 18-65 years of age, with:

1. DSM-IV diagnosis of MDD without psychosis (single episode or recurrent) confirmed by the Mini-International Neuro-psychiatric Interview (MINI)
2. MADRS total score > 20, and item 1 (Apparent Sadness) score > 2 at enrollment and randomization
3. Inadequate therapeutic response during their current depressive episode; an inadequate therapeutic response will be defined as continued depressive psychopathology (see criterion 2) following > six weeks of therapy at adequate doses (according to the US label) of any non-tricyclic, non-MAOI antidepressant medication

Exclusion Criteria:

1. Additional DSM-IV Axis I diagnoses other than Generalized Anxiety Disorder, Panic Disorder with or without Agoraphobia, or Social Phobia within 6 months prior to enrollment
2. DSM-IV Axis II diagnoses that significantly impact the current psychiatric status
3. Current MDD episode lasting > 12 months
4. Electroconvulsive therapy within the preceding 6 months
5. Substance or alcohol dependence, as defined by DSM-IV criteria, within 6 months prior to enrollment
6. Unstable medical illness, epilepsy, traumatic brain injury, Parkinson disease, or dementia (MMSE <24)
7. Risk of suicide as defined by MADRS item 10 score > 4
8. Prior failure to respond to asenapine
9. Pregnancy or failure to use an acceptable form of birth control. Pregnancy as determined by serum pregnancy test at baseline
10. Hepatic impairment and history of low WBC, by medical history and interview.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Asenapine 5-20 mg daily; Asenapine will be started at 5 mg BID. The asenapine dose can be increased to 15 mg daily and then to 20 mg daily, or reduced to 5 mg daily, depending on therapeutic response and tolerability	Drug: Asenapine 5-20 mg daily; 5 mg QHS, or 5 mg BID, or 5 mg QAM and 10 mg QHS, or 10 mg BID; Other Names: SAPHRIS
Placebo Comparator: Placebo 1-4 tablets daily; Matched, blinded placebo tablets will be administered at doses from 1-4 tablets daily depending on therapeutic response and tolerability	Drug: Placebo 1-4 tablets daily; One placebo tablet QHS, or one placebo tablet BID, or one placebo tablet QAM and two placebo tablets QHS, or two placebo tablets BID; Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in MADRS Total Score	The Montgomery Asberg Depression Rating Scale (MADRS) is used by clinicians to assess the severity of depression among patients with a diagnosis of depression. It is designed to be sensitive to change resulting from antidepressant therapy. MADRS is a 10-item scale. Each MADRS item is rated on a 0 to 6 scale. The MADRS Total score ranges from 0 (min) to 60 (max). Higher MADRS scores indicate higher levels of depressive symptoms.	Baseline, 6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Study Completion Rate	The percentage of patients completing the study in their assigned treatment arm (asenapine or placebo) at the end of 6 weeks	6 weeks
Clinical Response Rate	Clinical Response rate will be defined as the number of participants with a > 50% reduction from baseline in MADRS total score. MADRS is a 10-item scale. Each MADRS item is rated on a 0 to 6 scale. The MADRS Total score ranges from 0 (min) to 60 (max). Higher MADRS scores indicate higher levels of depressive symptoms.	Baseline, 6 weeks
Clinical Remission Rate	Clinical Remission will be defined as the number of participants with a MADRS total score < 7. MADRS is a 10-item scale. Each MADRS item is rated on a 0 to 6 scale. The MADRS Total score ranges from 0 (min) to 60 (max). Higher MADRS scores indicate higher levels of depressive symptoms.	6 weeks
Rates of Sustained Remission	Sustained remission will be defined as at least two consecutive post-randomization assessments (weeks 2, 4, and 6) during which minimal depressive psychopathology (MADRS < 7) is present. MADRS is a 10-item scale. Each MADRS item is rated on a 0 to 6 scale. The MADRS Total score ranges from 0 (min) to 60 (max). Higher MADRS scores indicate higher levels of depressive symptoms.	2, 4, 6 weeks

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: John Beyer, MD, Duke University

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (Actual): May 1, 2014
• Study Completion (Actual): June 1, 2014

Study Registration Dates

• First Submitted: August 17, 2012
• First Submitted That Met QC Criteria: August 17, 2012
• First Posted (Estimate): August 21, 2012

Study Record Updates

• Last Update Posted (Estimate): October 1, 2015
• Last Update Submitted That Met QC Criteria: August 31, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Keywords: Depression; Antidepressant; Antipsychotic
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major; Physiological Effects of Drugs; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Asenapine
• Other Study ID Numbers: Pro00037462