A Study Of The Efficacy And Safety Of CP-601,927 Augmentation Of Antidepressant Therapy In Major Depression

Study Overview
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Brief Summary
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The primary objectives of this study are to: 1) Evaluate the efficacy of CP 601,927 compared to placebo in the augmentation of antidepressant therapy (ADT) in patients with Major Depressive Disorder (MDD) using the Montgomery Asberg Depression Rating Scale (MADRS). 2) Evaluate the safety and tolerability of CP 601,927 in patients with MDD on ADT.

Detailed Description
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The study was stopped at interim analysis in August 2011, as stopping criteria for futility were met. There was no statistically significant change on the primary efficacy scale in favor of the drug. There was a very small chance that any additional data could change the study overall outcome. There were no concerns regarding subject safety.

Official Title
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A RANDOMIZED PHASE 2A, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF THE EFFICACY AND SAFETY OF CP-601,927 AUGMENTATION OF ANTIDEPRESSANT THERAPY IN MAJOR DEPRESSION

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: CP-601,927
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Medically healthy males or females aged 18-65 (inclusive). Patients must have a primary current diagnosis of MDD without psychotic features. Patients must be receiving ongoing antidepressant therapy at the time of screening. Duration of the current episode of MDD must be at least 8 weeks prior to enrollment without adequate response to treatment. Exclusion Criteria: Patients with other psychiatric disorders. Patients who use tobacco products. Alcohol or substance abuse or dependence. Treatment with a monoamine oxidase inhibitor within 10 weeks of enrollment. Pregnancy or breastfeeding. Clinically significant abnormalities on laboratory tests, electrocardiogram, or physical or neurologic examination.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active Treatment<br>CP-601,927 | Drug: CP-601,927<br>* CP-601,927 1-2 mg twice per day, oral 1 mg tablets, for 6 weeks.<br>|
| Placebo Comparator: Placebo<br>Placebo | Other: Placebo<br>* Matching placebo tablets, taken orally, twice per day, for 6 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Double-blind Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) - Total Score at Week 14 | MADRS measures the overall severity of depressive symptoms. The MADRS had a 10-item checklist. Items are rated on a scale of 0-6, for a total numeric range of scores from 0 (depressive symptoms absent) to 60 (numerically highest level of depressive symptoms). | Week 8 (double-blind baseline ) and week 14 (week 6 of double-blind phase) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Double-blind Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) - Total Score at Weeks 9 Through 13 | MADRS measures the overall severity of depressive symptoms. The MADRS had a 10-item checklist. Items are rated on a scale of 0-6, for a total numeric range of scores from 0 (depressive symptoms absent) to 60 (numerically highest level of depressive symptoms). | Week 8 (double-blind baseline) and weeks 9 through 13 | 
| Change From Double-blind Baseline in Hamilton Depression Scale 25-item (HAM-D25) - Total Score at Weeks 9 Through 14 | The HAM-D25 is the 25-item version of a scale used to assess the range of depressive symptoms including depressed mood, work and activities, sleep, suicidal thinking, psychomotor agitation/retardation, appetite, sexual interest, anxiety, somatic symptoms, and cognitive symptoms. The items on the HAM-D were rated on a scale of 0-2 or 0-4, for a total numeric range of scores from 0 (depressive symptoms absent) to 72 (numerically highest level of depressive symptoms). | Weeks 8 (double-blind baseline) through 14 | 
| Change From Double-blind Baseline in Bech Melancholia Subscale Score at Weeks 9 Through 14 | The Bech Melancholia is sum of scores on 6 items (items 1, 2, 7, 8, 10 and 13) pertaining to melancholia within HAM-D. The items are rated on a scale of 0-4, higher scores reflecting greater severity. Total possible score is 0-24. | Weeks 8 (double-blind baseline) through 14 | 
| Change From Double-blind Baseline in Clinical Global Impression - Severity (CGI-S) at Weeks 9, 10, 12, and 14 | CGI-S was defined as 7-point clinician rated scale to assess severity of participant's current illness state; range: 1 (normal - not ill at all) to 7 (among the most extremely ill participants). Higher score = more affected. | Week 8 (double-blind baseline) and weeks 9, 10, 12, 14 | 
| Change From Double-blind Baseline in Sheehan Irritability Scale (SIS) Total Score at Weeks 11 and 14 | The SIS is to rate suffering with regard to irritability symptoms. The degree to which irritability interferes with work, social and family function is also queried. The total SIS score is the sum of 7 items. Each item is rated on a scale of 0-10, for a total numeric range of scores from 0 (not at all) to 70 (extremely). The SIS also records the number of days impaired by irritability. | Weeks 8 (double-blind baseline), 11 and 14 | 
| Change From Double-blind Baseline in Sheehan Disability Scale (SDS) Total Score at Weeks 11 and 14 | SDS is defined as a self-administered tool that measures functional impairment including work/school, social life, and family life/home responsibilities. Items are rated on a scale of 0-10 visual analog scale (0=not at all impaired, 10=extremely impaired), for a total numeric range of scores from 0 (not at all impaired) to 30 (extremely impaired). | Weeks 8 (double-blind baseline), 11 and 14 | 
| Change From Double-blind Baseline in Sheehan Disability Scale (SDS) Subscale Score at Weeks 11 and 14 | SDS subscale is defined as a self-administered tool that measures functional impairment in 3-item including work/school, social life, and family life/home responsibilities. Items are rated on a scale of 0-10 visual analog scale, for a total numeric range of scores from 0 (not at all impaired) to 30 (extremely impaired). | Weeks 8 (double-blind baseline), 11 and 14 | 
| Clinical Global Impression - Improvement (CGI-I) Total Score at Weeks 9, 10, 12 and 14 | CGI-I was defined as a 7-point clinician rated scale ranging from 1 (very much improved) to 7 (very much worse). Improvement was defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale. Higher score = more affected. | Weeks 8 (double-blind baseline) 9, 10, 12 and 14 | 
| Number of Participants With Remission at Weeks 9, 10, 12 and 14 | Remission was defined as response plus an absolute MADRS total score of less than or equal to 10 plus a CGI-I score less than 2 ('much' or 'very much' improved). | Weeks 9, 10, 12 and 14 | 
| Number of Participants With Response at Weeks 9 Through 14 | Response was defined as greater than 50 percent reduction from double-blind baseline in MADRS total score. | Weeks 9 through 14 | 
| Population Pharmacokinetics | Population pharmacokinetic analysis involved mixed effects modeling using nonlinear mixed effects modeling (NONMEM) software. The intent of this analysis was to establish a basic population pharmacokinetic model for CP-601,927 and to determine inter-individual and residual variability in population clearance, and volume of distribution of drug. Relationship of demographic variables (gender, age, body weight, height and ethnicity), concomitant medications and measures of altered hepatic and renal function were examined by fitting measured CP-601,927 concentrations | Weeks 11,12 and 14 | 
| Plasma CP-601,927 Concentration | Blood samples were collected for plasma CP-601,927 concentration analysis which was summarized by mean and standard deviation. | Week 11, 12 and 14 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Antidepressant Augmentation