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

Phase 2
Terminated
Conditions
Major Depressive Disorder
Interventions
Drug: CP-601,927
Other: Placebo
Registration Number
NCT01098240
Lead Sponsor
Pfizer
Brief Summary

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

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.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
297
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Active TreatmentCP-601,927CP-601,927
PlaceboPlaceboPlacebo
Primary Outcome Measures
NameTimeMethod
Change From Double-blind Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) - Total Score at Week 14Week 8 (double-blind baseline ) and week 14 (week 6 of double-blind phase)

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).

Secondary Outcome Measures
NameTimeMethod
Change From Double-blind Baseline in Hamilton Depression Scale 25-item (HAM-D25) - Total Score at Weeks 9 Through 14Weeks 8 (double-blind baseline) 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).

Change From Double-blind Baseline in Clinical Global Impression - Severity (CGI-S) at Weeks 9, 10, 12, and 14Week 8 (double-blind baseline) and weeks 9, 10, 12, 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.

Change From Double-blind Baseline in Sheehan Irritability Scale (SIS) Total Score at Weeks 11 and 14Weeks 8 (double-blind baseline), 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.

Change From Double-blind Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) - Total Score at Weeks 9 Through 13Week 8 (double-blind baseline) and 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).

Change From Double-blind Baseline in Bech Melancholia Subscale Score at Weeks 9 Through 14Weeks 8 (double-blind baseline) 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.

Clinical Global Impression - Improvement (CGI-I) Total Score at Weeks 9, 10, 12 and 14Weeks 8 (double-blind baseline) 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.

Change From Double-blind Baseline in Sheehan Disability Scale (SDS) Total Score at Weeks 11 and 14Weeks 8 (double-blind baseline), 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).

Number of Participants With Remission at Weeks 9, 10, 12 and 14Weeks 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).

Number of Participants With Response at Weeks 9 Through 14Weeks 9 through 14

Response was defined as greater than 50 percent reduction from double-blind baseline in MADRS total score.

Change From Double-blind Baseline in Sheehan Disability Scale (SDS) Subscale Score at Weeks 11 and 14Weeks 8 (double-blind baseline), 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).

Population PharmacokineticsWeeks 11,12 and 14

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

Plasma CP-601,927 ConcentrationWeek 11, 12 and 14

Blood samples were collected for plasma CP-601,927 concentration analysis which was summarized by mean and standard deviation.

Trial Locations

Locations (55)

Southwestern Research Incorporated

🇺🇸

Beverly Hills, California, United States

Synergy Clinical Research Center

🇺🇸

National City, California, United States

Collaborative Neuroscience Network, Inc.

🇺🇸

Garden Grove, California, United States

Comprehensive Psychiatric Care

🇺🇸

Norwich, Connecticut, United States

Clinical Neuroscience Solutions, Inc.

🇺🇸

Orlando, Florida, United States

Florida Clinical Research Center, LLC

🇺🇸

Maitland, Florida, United States

Comprehensive NeuroScience, Inc.

🇺🇸

Fresh Meadows, New York, United States

Atlanta Institute of Medicine and Research

🇺🇸

Atlanta, Georgia, United States

Atlanta Center for Medical Research

🇺🇸

Atlanta, Georgia, United States

AMR-Baber Research Inc.

🇺🇸

Naperville, Illinois, United States

Psychiatric Medicine Associates, LLC.

🇺🇸

Skokie, Illinois, United States

Clinco

🇺🇸

Terre Haute, Indiana, United States

Louisiana Clinical Research, LLC

🇺🇸

Shreveport, Louisiana, United States

Massachusetts General Hospital

🇺🇸

Boston, Massachusetts, United States

AccelRx Research

🇺🇸

Fall River, Massachusetts, United States

Detroit Bio-Medical Laboratories, Inc.

🇺🇸

Rochester Hills, Michigan, United States

Rochester Center for Behavioral Medicine

🇺🇸

Rochester Hills, Michigan, United States

St. Charles Psychiatric Associates - Midwest Research Group

🇺🇸

Saint Charles, Missouri, United States

Midwest Clinical Research Center

🇺🇸

Dayton, Ohio, United States

Social Psychiatry Research Institute

🇺🇸

Brooklyn, New York, United States

Erie County Medical Center / State University of New York at Buffalo affiliate

🇺🇸

Buffalo, New York, United States

Neurology and Neuroscience Center of Ohio

🇺🇸

Toledo, Ohio, United States

Kettlie Joseph Daniels, MD, Inc.

🇺🇸

Toledo, Ohio, United States

Suburban Research Associates

🇺🇸

Media, Pennsylvania, United States

Lehigh Valley Health Network

🇺🇸

Allentown, Pennsylvania, United States

City Line Family Medicine

🇺🇸

Bala-Cynwyd, Pennsylvania, United States

University of Pennsylvania / Department of Psychiatry

🇺🇸

Philadelphia, Pennsylvania, United States

Frankford Avenue Family Practice, PC

🇺🇸

Philadelphia, Pennsylvania, United States

Lincoln Research

🇺🇸

Lincoln, Rhode Island, United States

FutureSearch Trials

🇺🇸

Austin, Texas, United States

FutureSearch Trials of Dallas, L.P.

🇺🇸

Dallas, Texas, United States

InSite Clinical Research

🇺🇸

DeSoto, Texas, United States

University of Texas (UT) Southwestern Medical Center at Dallas

🇺🇸

Dallas, Texas, United States

University of Virginia Health System / Department of Psychiatry and Neurobehavioral Sciences

🇺🇸

Charlottesville, Virginia, United States

Mcguire Hall Annex

🇺🇸

Richmond, Virginia, United States

Nelson Clinic

🇺🇸

Richmond, Virginia, United States

Dean Foundation for Health, Research and Education

🇺🇸

Middleton, Wisconsin, United States

Northbrooke Research Center

🇺🇸

Brown Deer, Wisconsin, United States

Heartland Research Associates, LLC

🇺🇸

Wichita, Kansas, United States

Arkansas Psychiatric Clinic Clinical Research Trials, P.A.

🇺🇸

Little Rock, Arkansas, United States

William B. Backus Hospital Satellite Blood Draw

🇺🇸

Norwich, Connecticut, United States

Lake Charles Clinical Trials

🇺🇸

Lake Charles, Louisiana, United States

Louisiana Research Associates, Inc.

🇺🇸

New Orleans, Louisiana, United States

Center for Emotional Fitness

🇺🇸

Cherry Hill, New Jersey, United States

Carolina Clinical Research Service LLC

🇺🇸

Columbia, South Carolina, United States

Artemis Institute for Clinical Research

🇺🇸

San Diego, California, United States

Goldpoint Clinical Research, LLC

🇺🇸

Indianapolis, Indiana, United States

Cutting Edge Research Group

🇺🇸

Oklahoma City, Oklahoma, United States

Radiant Research, Inc

🇺🇸

Salt Lake City, Utah, United States

University of Utah School of Medicine Department of Psychiatry Mood Disorders Clinic

🇺🇸

Salt Lake City, Utah, United States

Radiant Research, Inc.

🇺🇸

Denver, Colorado, United States

IPS Research

🇺🇸

Oklahoma City, Oklahoma, United States

Summit Research Network (Oregon), Inc.

🇺🇸

Portland, Oregon, United States

Virginia Commonwealth University (VCU) Medical Center

🇺🇸

Richmond, Virginia, United States

Montefiore Medical Center

🇺🇸

Bronx, New York, United States

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