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

This study has been terminated.
(See termination reason in detailed description.)
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01098240
First received: April 1, 2010
Last updated: July 18, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention Phase
Major Depressive Disorder
Drug: CP-601,927
Other: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Change From Double-blind Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) - Total Score at Week 14 [ Time Frame: Week 8 (double-blind baseline ) and week 14 (week 6 of double-blind phase) ] [ Designated as safety issue: No ]
    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:
  • Change From Double-blind Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) - Total Score at Weeks 9 Through 13 [ Time Frame: Week 8 (double-blind baseline) and weeks 9 through 13 ] [ Designated as safety issue: No ]
    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 Hamilton Depression Scale 25-item (HAM-D25) - Total Score at Weeks 9 Through 14 [ Time Frame: Weeks 8 (double-blind baseline) through 14 ] [ Designated as safety issue: No ]
    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 Bech Melancholia Subscale Score at Weeks 9 Through 14 [ Time Frame: Weeks 8 (double-blind baseline) through 14 ] [ Designated as safety issue: No ]
    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.

  • Change From Double-blind Baseline in Clinical Global Impression - Severity (CGI-S) at Weeks 9, 10, 12, and 14 [ Time Frame: Week 8 (double-blind baseline) and weeks 9, 10, 12, 14 ] [ Designated as safety issue: No ]
    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 14 [ Time Frame: Weeks 8 (double-blind baseline), 11 and 14 ] [ Designated as safety issue: No ]
    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 Sheehan Disability Scale (SDS) Total Score at Weeks 11 and 14 [ Time Frame: Weeks 8 (double-blind baseline), 11 and 14 ] [ Designated as safety issue: No ]
    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).

  • Change From Double-blind Baseline in Sheehan Disability Scale (SDS) Subscale Score at Weeks 11 and 14 [ Time Frame: Weeks 8 (double-blind baseline), 11 and 14 ] [ Designated as safety issue: Yes ]
    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).

  • Clinical Global Impression - Improvement (CGI-I) Total Score at Weeks 9, 10, 12 and 14 [ Time Frame: Weeks 8 (double-blind baseline) 9, 10, 12 and 14 ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Remission at Weeks 9, 10, 12 and 14 [ Time Frame: Weeks 9, 10, 12 and 14 ] [ Designated as safety issue: No ]
    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 14 [ Time Frame: Weeks 9 through 14 ] [ Designated as safety issue: No ]
    Response was defined as greater than 50 percent reduction from double-blind baseline in MADRS total score.

  • Population Pharmacokinetics [ Time Frame: Weeks 11,12 and 14 ] [ Designated as safety issue: No ]
    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 Concentration [ Time Frame: Week 11, 12 and 14 ] [ Designated as safety issue: No ]
    Blood samples were collected for plasma CP-601,927 concentration analysis which was summarized by mean and standard deviation.


Other Outcome Measures:
  • The Sheehan Suicidality Tracking Scale (STS) [ Time Frame: Week 8 (double-blind baseline) and weeks 9 through 14 ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 297
Study Start Date: June 2010
Study Completion Date: September 2011
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Placebo Comparator: Placebo
Placebo
Other: Placebo
Matching placebo tablets, taken orally, twice per day, for 6 weeks.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01098240

  Show 55 Study Locations
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01098240     History of Changes
Other Study ID Numbers: A3331017
Study First Received: April 1, 2010
Results First Received: September 18, 2012
Last Updated: July 18, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
Antidepressant Augmentation

Additional relevant MeSH terms:
Depression
Depressive Disorder
Depressive Disorder, Major
Behavioral Symptoms
Mood Disorders
Mental Disorders
Antidepressive Agents
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 15, 2014