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

• ClinicalTrials.gov Identifier: NCT01098240
• Recruitment Status: Terminated
• First Posted: April 2, 2010
• Results First Posted: June 26, 2013
• Last Update Posted: July 29, 2019
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: April 1, 2010
• First Posted Date: April 2, 2010
• Results First Submitted Date: September 18, 2012
• Results First Posted Date: June 26, 2013
• Last Update Posted Date: July 29, 2019
• Study Start Date: June 2010
• Actual Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 18, 2013)

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) ]

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).

Original Primary Outcome Measures (submitted: April 1, 2010)

• Change from double blind baseline in MADRS total score at Week 14 (after 6 weeks of double blind therapy). [ Time Frame: 6 weeks ]
• Vital signs, ECG, adverse events, physical examination findings, safety laboratory assessments, STS score. [ Time Frame: 6 weeks ]

Current Secondary Outcome Measures (submitted: July 18, 2013)

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

Original Secondary Outcome Measures (submitted: April 1, 2010)

• Change from double blind baseline at Weeks 9-14 in HAM D25 total score, Bech Melancholia subscale score, CGI S score, SDS score, and at Weeks 11 and 14 in SIS score. [ Time Frame: 2 and 6 weeks ]
• Change from double-blind baseline at Weeks 9-13 in MADRS total score. [ Time Frame: Weekly ]
• Total CGI I score at Weeks 9-14. [ Time Frame: Weekly ]
• Response rates, defined as >50% reduction from double-blind baseline in MADRS total score, at Weeks 9-14. [ Time Frame: Weekly ]
• Remission rates, defined as response plus an absolute MADRS total score of less than or equal to 10 plus a CGI I score <2 ("much" or "very much" improved), at Weeks 9-14. [ Time Frame: Weekly ]

Current Other Pre-specified Outcome Measures (submitted: May 17, 2013)

The Sheehan Suicidality Tracking Scale (STS) [ Time Frame: Week 8 (double-blind baseline) and weeks 9 through 14 ]

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.

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study Of The Efficacy And Safety Of CP-601,927 Augmentation Of Antidepressant Therapy In Major Depression
• 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
• 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.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Major Depressive Disorder

Intervention

• Drug: CP-601,927
  CP-601,927 1-2 mg twice per day, oral 1 mg tablets, for 6 weeks.
• Other: Placebo
  Matching placebo tablets, taken orally, twice per day, for 6 weeks.

Study Arms

• Experimental: Active Treatment
  CP-601,927
  Intervention: Drug: CP-601,927
• Placebo Comparator: Placebo
  Placebo
  Intervention: Other: Placebo

• 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.

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: May 17, 2013): 297
• Original Estimated Enrollment (submitted: April 1, 2010): 198
• Actual Study Completion Date: September 2011
• Actual Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01098240
• Other Study ID Numbers: A3331017
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Pfizer
• Study Sponsor: Pfizer
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: July 2019