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

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

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.

Study Overview

• Status: Terminated
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: CP-601,927; Other: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 297
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72223
      • Arkansas Psychiatric Clinic Clinical Research Trials, P.A.
  • California
    • Beverly Hills, California, United States, 90210
      • Southwestern Research Incorporated
    • Garden Grove, California, United States, 92845
      • Collaborative Neuroscience Network, Inc.
    • National City, California, United States, 91950
      • Synergy Clinical Research Center
    • San Diego, California, United States, 92123
      • Artemis Institute for Clinical Research
  • Colorado
    • Denver, Colorado, United States, 80239
      • Radiant Research, Inc.
  • Connecticut
    • Norwich, Connecticut, United States, 06360
      • Comprehensive Psychiatric Care
    • Norwich, Connecticut, United States, 06360
      • William B. Backus Hospital Satellite Blood Draw
  • Florida
    • Jacksonville, Florida, United States, 32216
      • Clinical Neuroscience Solutions, INC.
    • Maitland, Florida, United States, 32751
      • Florida Clinical Research Center, LLC
    • Orlando, Florida, United States, 32806
      • Clinical Neuroscience Solutions, INC.
    • Saint Petersburg, Florida, United States, 33716
      • Comprehensive NeuroScience, Inc.
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Atlanta Center for Medical Research
    • Atlanta, Georgia, United States, 30328
      • Atlanta Institute of Medicine and Research
  • Illinois
    • Naperville, Illinois, United States, 60563
      • AMR-Baber Research Inc.
    • Skokie, Illinois, United States, 60076
      • Psychiatric Medicine Associates, LLC.
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Goldpoint Clinical Research, LLC
    • Terre Haute, Indiana, United States, 47802
      • Clinco
  • Kansas
    • Wichita, Kansas, United States, 67207
      • Heartland Research Associates, LLC
  • Louisiana
    • Lake Charles, Louisiana, United States, 70629
      • Lake Charles Clinical Trials
    • New Orleans, Louisiana, United States, 70114
      • Louisiana Research Associates, Inc.
    • Shreveport, Louisiana, United States, 71115
      • Louisiana Clinical Research, LLC
  • Massachusetts
    • Boston, Massachusetts, United States, 02171
      • Massachusetts General Hospital
    • Fall River, Massachusetts, United States, 02721
      • AccelRx Research
  • Michigan
    • Rochester Hills, Michigan, United States, 48307
      • Rochester Center for Behavioral Medicine
    • Rochester Hills, Michigan, United States, 48307
      • Detroit Bio-Medical Laboratories, Inc.
  • Missouri
    • Saint Charles, Missouri, United States, 63301
      • St. Charles Psychiatric Associates - Midwest Research Group
  • New Jersey
    • Cherry Hill, New Jersey, United States, 08002
      • Center for Emotional Fitness
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center
    • Brooklyn, New York, United States, 11235
      • Social Psychiatry Research Institute
    • Buffalo, New York, United States, 14215
      • Erie County Medical Center / State University of New York at Buffalo affiliate
    • Fresh Meadows, New York, United States, 11366
      • Comprehensive NeuroScience, Inc.
  • Ohio
    • Dayton, Ohio, United States, 45417
      • Midwest Clinical Research Center
    • Toledo, Ohio, United States, 43623
      • Neurology and Neuroscience Center of Ohio
    • Toledo, Ohio, United States, 43609
      • Kettlie Joseph Daniels, MD, Inc.
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73116
      • Cutting Edge Research Group
    • Oklahoma City, Oklahoma, United States, 73103
      • IPS Research
  • Oregon
    • Portland, Oregon, United States, 97210
      • Summit Research Network (Oregon), Inc.
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18103
      • Lehigh Valley Health Network
    • Bala-Cynwyd, Pennsylvania, United States, 19004
      • City Line Family Medicine
    • Media, Pennsylvania, United States, 19063
      • Suburban Research Associates
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania / Department of Psychiatry
    • Philadelphia, Pennsylvania, United States, 19136
      • Frankford Avenue Family Practice, PC
  • Rhode Island
    • Lincoln, Rhode Island, United States, 02865
      • Lincoln Research
  • South Carolina
    • Columbia, South Carolina, United States, 29201
      • Carolina Clinical Research Service LLC
  • Texas
    • Austin, Texas, United States, 78731
      • FutureSearch Trials
    • Dallas, Texas, United States, 75231
      • FutureSearch Trials of Dallas, L.P.
    • Dallas, Texas, United States, 75235
      • University of Texas (UT) Southwestern Medical Center at Dallas
    • Dallas, Texas, United States, 75390-9119
      • University of Texas (UT) Southwestern Medical Center at Dallas
    • DeSoto, Texas, United States, 75115
      • InSite Clinical Research
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • Radiant Research, Inc
    • Salt Lake City, Utah, United States, 84132
      • University of Utah School of Medicine Department of Psychiatry Mood Disorders Clinic
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia Health System / Department of Psychiatry and Neurobehavioral Sciences
    • Richmond, Virginia, United States, 23219
      • Mcguire Hall Annex
    • Richmond, Virginia, United States, 23219
      • Nelson Clinic
    • Richmond, Virginia, United States, 23298-0155
      • Virginia Commonwealth University (VCU) Medical Center
  • Wisconsin
    • Brown Deer, Wisconsin, United States, 53223
      • Northbrooke Research Center
    • Middleton, Wisconsin, United States, 53562
      • Dean Foundation for Health, Research and Education

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:

• 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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Sheehan Suicidality Tracking Scale (STS)	The Sheehan Suicidality Tracking Scale (STS) measures treatment-emergent suicidal ideation as well as behaviors. It can be administered by a clinician or filled in by a participant. Prior to analysis, the STS was mapped to the Columbia Classification Algorithm of Suicide Assessment(C-CASA) categories, which has 9-item including completed suicide, suicide attempt, preparatory acts, suicidal ideation, self-injurious behavior, self-injurious no intent, unknown fatal,unknown non-fatal or other not deliberate. Participants who were mapped to C-CASA items were reported.	Week 8 (double-blind baseline) and weeks 9 through 14

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Fava M, Ramey T, Pickering E, Kinrys G, Boyer S, Altstiel L. A randomized, double-blind, placebo-controlled phase 2 study of the augmentation of a nicotinic acetylcholine receptor partial agonist in depression: is there a relationship to leptin levels? J Clin Psychopharmacol. 2015 Feb;35(1):51-6. doi: 10.1097/JCP.0000000000000245.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): June 14, 2010
• Primary Completion (Actual): September 12, 2011
• Study Completion (Actual): September 12, 2011

Study Registration Dates

• First Submitted: April 1, 2010
• First Submitted That Met QC Criteria: April 1, 2010
• First Posted (Estimate): April 2, 2010

Study Record Updates

• Last Update Posted (Actual): May 3, 2021
• Last Update Submitted That Met QC Criteria: April 7, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Antidepressant Augmentation
• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; Depressive Disorder, Major
• Other Study ID Numbers: A3331017

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.