A Study Of The Efficacy And Safety Of CP-601,927 Augmentation Of Antidepressant Therapy In Major Depression
Sponsor
Pfizer (Industry)
Overall Status
Terminated
CT.gov ID
NCT01098240
Collaborator
(none)
297
58
2
14.9
5.1
0.3
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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 Design
Study Type:
Interventional
Actual Enrollment
:
297 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, 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
Actual Study Start Date
:
Jun 14, 2010
Actual Primary Completion Date
:
Sep 12, 2011
Actual Study Completion Date
:
Sep 12, 2011
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| 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.
|
Outcome Measures
Primary Outcome Measures
- Change From Double-blind Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) - Total Score at Week 14 [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).
Secondary Outcome Measures
- Change From Double-blind Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) - Total Score at Weeks 9 Through 13 [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 [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 [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 [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 [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 [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 [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 [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 [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 [Weeks 9 through 14]
Response was defined as greater than 50 percent reduction from double-blind baseline in MADRS total score.
- Population Pharmacokinetics [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 [Week 11, 12 and 14]
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) [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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 65 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Arkansas Psychiatric Clinic Clinical Research Trials, P.A. | Little Rock | Arkansas | United States | 72223 |
| 2 | Southwestern Research Incorporated | Beverly Hills | California | United States | 90210 |
| 3 | Collaborative Neuroscience Network, Inc. | Garden Grove | California | United States | 92845 |
| 4 | Synergy Clinical Research Center | National City | California | United States | 91950 |
| 5 | Artemis Institute for Clinical Research | San Diego | California | United States | 92123 |
| 6 | Radiant Research, Inc. | Denver | Colorado | United States | 80239 |
| 7 | Comprehensive Psychiatric Care | Norwich | Connecticut | United States | 06360 |
| 8 | William B. Backus Hospital Satellite Blood Draw | Norwich | Connecticut | United States | 06360 |
| 9 | Clinical Neuroscience Solutions, Inc. | Jacksonville | Florida | United States | 32216 |
| 10 | Florida Clinical Research Center, LLC | Maitland | Florida | United States | 32751 |
| 11 | Clinical Neuroscience Solutions, Inc. | Orlando | Florida | United States | 32806 |
| 12 | Comprehensive NeuroScience, Inc. | Saint Petersburg | Florida | United States | 33716 |
| 13 | Atlanta Center for Medical Research | Atlanta | Georgia | United States | 30308 |
| 14 | Atlanta Institute of Medicine and Research | Atlanta | Georgia | United States | 30328 |
| 15 | AMR-Baber Research Inc. | Naperville | Illinois | United States | 60563 |
| 16 | Psychiatric Medicine Associates, LLC. | Skokie | Illinois | United States | 60076 |
| 17 | Goldpoint Clinical Research, LLC | Indianapolis | Indiana | United States | 46260 |
| 18 | Clinco | Terre Haute | Indiana | United States | 47802 |
| 19 | Heartland Research Associates, LLC | Wichita | Kansas | United States | 67207 |
| 20 | Lake Charles Clinical Trials | Lake Charles | Louisiana | United States | 70629 |
| 21 | Louisiana Research Associates, Inc. | New Orleans | Louisiana | United States | 70114 |
| 22 | Louisiana Clinical Research, LLC | Shreveport | Louisiana | United States | 71115 |
| 23 | Massachusetts General Hospital | Boston | Massachusetts | United States | 02171 |
| 24 | AccelRx Research | Fall River | Massachusetts | United States | 02721 |
| 25 | Detroit Bio-Medical Laboratories, Inc. | Rochester Hills | Michigan | United States | 48307 |
| 26 | Rochester Center for Behavioral Medicine | Rochester Hills | Michigan | United States | 48307 |
| 27 | St. Charles Psychiatric Associates - Midwest Research Group | Saint Charles | Missouri | United States | 63301 |
| 28 | Center for Emotional Fitness | Cherry Hill | New Jersey | United States | 08002 |
| 29 | Montefiore Medical Center | Bronx | New York | United States | 10467 |
| 30 | Social Psychiatry Research Institute | Brooklyn | New York | United States | 11235 |
| 31 | Erie County Medical Center / State University of New York at Buffalo affiliate | Buffalo | New York | United States | 14215 |
| 32 | Comprehensive NeuroScience, Inc. | Fresh Meadows | New York | United States | 11366 |
| 33 | Midwest Clinical Research Center | Dayton | Ohio | United States | 45417 |
| 34 | Kettlie Joseph Daniels, MD, Inc. | Toledo | Ohio | United States | 43609 |
| 35 | Neurology and Neuroscience Center of Ohio | Toledo | Ohio | United States | 43623 |
| 36 | IPS Research | Oklahoma City | Oklahoma | United States | 73103 |
| 37 | Cutting Edge Research Group | Oklahoma City | Oklahoma | United States | 73116 |
| 38 | Summit Research Network (Oregon), Inc. | Portland | Oregon | United States | 97210 |
| 39 | Lehigh Valley Health Network | Allentown | Pennsylvania | United States | 18103 |
| 40 | City Line Family Medicine | Bala-Cynwyd | Pennsylvania | United States | 19004 |
| 41 | Suburban Research Associates | Media | Pennsylvania | United States | 19063 |
| 42 | University of Pennsylvania / Department of Psychiatry | Philadelphia | Pennsylvania | United States | 19104 |
| 43 | Frankford Avenue Family Practice, PC | Philadelphia | Pennsylvania | United States | 19136 |
| 44 | Lincoln Research | Lincoln | Rhode Island | United States | 02865 |
| 45 | Carolina Clinical Research Service LLC | Columbia | South Carolina | United States | 29201 |
| 46 | FutureSearch Trials | Austin | Texas | United States | 78731 |
| 47 | FutureSearch Trials of Dallas, L.P. | Dallas | Texas | United States | 75231 |
| 48 | University of Texas (UT) Southwestern Medical Center at Dallas | Dallas | Texas | United States | 75235 |
| 49 | University of Texas (UT) Southwestern Medical Center at Dallas | Dallas | Texas | United States | 75390-9119 |
| 50 | InSite Clinical Research | DeSoto | Texas | United States | 75115 |
| 51 | Radiant Research, Inc | Salt Lake City | Utah | United States | 84107 |
| 52 | University of Utah School of Medicine Department of Psychiatry Mood Disorders Clinic | Salt Lake City | Utah | United States | 84132 |
| 53 | University of Virginia Health System / Department of Psychiatry and Neurobehavioral Sciences | Charlottesville | Virginia | United States | 22903 |
| 54 | Mcguire Hall Annex | Richmond | Virginia | United States | 23219 |
| 55 | Nelson Clinic | Richmond | Virginia | United States | 23219 |
| 56 | Virginia Commonwealth University (VCU) Medical Center | Richmond | Virginia | United States | 23298-0155 |
| 57 | Northbrooke Research Center | Brown Deer | Wisconsin | United States | 53223 |
| 58 | Dean Foundation for Health, Research and Education | Middleton | Wisconsin | United States | 53562 |
Sponsors and Collaborators
- Pfizer
Investigators
- Study Director: Pfizer CT.gov Call Center, Pfizer
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT01098240
Other Study ID Numbers:
- A3331017
First Posted:
Apr 2, 2010
Last Update Posted:
May 3, 2021
Last Verified:
Apr 1, 2021
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Keywords provided by Pfizer
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Open-Label Antidepressant Treatment (ADT) | CP-601,927 + ADT | Placebo + ADT |
|---|---|---|---|
| Arm/Group Description | Participants treated with 1 of 5 allowed antidepressant agents in accordance with current product labeling, targeting the following doses by the end of week 2: escitalopram (Lexapro) (10-20 milligram/day [mg/d]), citalopram (Celexa) (20-40 mg/d), fluoxetine (Prozac, Sarafem) (20-60 mg/d), paroxetine controlled-release (CR) (Paxil CR) (37.5-62.5 mg/d), sertraline (Zoloft) (100-200 mg/d), for up to 8 weeks in open-label phase. | Participants treated with CP-601,927 1 mg every evening (QPM) for 3 days, then 1 mg twice daily (BID) for 3 days, then 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase. | Placebo matched to CP-601,927 1 mg QPM for 3 days, then CP-601,927 1 mg BID for 3 days, and then CP-601,927 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase. |
| Period Title: Open-Label Phase | |||
| STARTED | 297 | 0 | 0 |
| COMPLETED | 162 | 0 | 0 |
| NOT COMPLETED | 135 | 0 | 0 |
| Period Title: Open-Label Phase | |||
| STARTED | 0 | 77 | 85 |
| COMPLETED | 0 | 60 | 63 |
| NOT COMPLETED | 0 | 17 | 22 |
Baseline Characteristics
| Arm/Group Title | Open-Label ADT |
|---|---|
| Arm/Group Description | Participants treated with 1 of 5 allowed antidepressant agents in accordance with current product labeling, targeting the following doses by the end of week 2: escitalopram (Lexapro) (10-20 mg/d), citalopram (Celexa) (20-40 mg/d), fluoxetine (Prozac, Sarafem) (20-60 mg/d), paroxetine CR (Paxil CR) (37.5-62.5 mg/d), sertraline (Zoloft) (100-200 mg/d), for up to 8 weeks in open-label phase. |
| Overall Participants | 297 |
| Age, Customized (Count of Participants) | |
| 18 to 44 years |
113
38%
|
| 45 to 64 years |
181
60.9%
|
| Greater than or equal to (>=) 65 years |
3
1%
|
| Sex: Female, Male (Count of Participants) | |
| Female |
220
74.1%
|
| Male |
77
25.9%
|
Outcome Measures
| Title | Change From Double-blind Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) - Total Score at Week 14 |
|---|---|
| Description | 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). |
| Time Frame | Week 8 (double-blind baseline ) and week 14 (week 6 of double-blind phase) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The full analysis set, which was defined as the set of all participants who consumed at least one dose of randomized study medication, was applied for the analysis. Number Analyzed = number of participants with evaluable data at each timeframe. |
| Arm/Group Title | CP-601,927 + ADT | Placebo + ADT |
|---|---|---|
| Arm/Group Description | Participants treated with CP-601,927 1 mg QPM for 3 days, then 1 mg BID for 3 days, then 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase. | Placebo matched to CP-601,927 1 mg QPM for 3 days, then CP-601,927 1 mg BID for 3 days, and then CP-601,927 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase. |
| Measure Participants | 77 | 85 |
| Week 8 (double-blind baseline) |
29.5
(6.00)
|
29.1
(5.54)
|
| Change at week 14 |
-10.3
(8.60)
|
-8.8
(10.40)
|
| Title | Change From Double-blind Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) - Total Score at Weeks 9 Through 13 |
|---|---|
| Description | 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). |
| Time Frame | Week 8 (double-blind baseline) and weeks 9 through 13 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The full analysis set, which was defined as the set of all participants who consumed at least one dose of randomized study medication, was applied for the analysis. Number Analyzed = number of participants with evaluable data at each timeframe. |
| Arm/Group Title | CP-601,927 + ADT | Placebo + ADT |
|---|---|---|
| Arm/Group Description | Participants treated with CP-601,927 1 mg QPM for 3 days, then 1 mg BID for 3 days, then 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase. | Placebo matched to CP-601,927 1 mg QPM for 3 days, then CP-601,927 1 mg BID for 3 days, and then CP-601,927 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase. |
| Measure Participants | 77 | 85 |
| Week 8 (double-blind baseline) |
29.5
(6.00)
|
29.1
(5.54)
|
| Change at Week 9 |
-2.4
(4.68)
|
-3.3
(5.35)
|
| Change at Week 10 |
-4.7
(6.65)
|
-4.6
(6.85)
|
| Change at Week 11 |
-7.0
(7.78)
|
-6.0
(8.06)
|
| Change at Week 12 |
-8.5
(8.08)
|
-7.4
(8.83)
|
| Change at week 13 |
-8.6
(8.16)
|
-7.9
(9.37)
|
| Title | Change From Double-blind Baseline in Hamilton Depression Scale 25-item (HAM-D25) - Total Score at Weeks 9 Through 14 |
|---|---|
| Description | 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). |
| Time Frame | Weeks 8 (double-blind baseline) through 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The full analysis set, which was defined as the set of all participants who consumed at least one dose of randomized study medication, was applied for the analysis. Number Analyzed = number of participants with evaluable data at each timeframe. |
| Arm/Group Title | CP-601,927 + ADT | Placebo + ADT |
|---|---|---|
| Arm/Group Description | Participants treated with CP-601,927 1 mg QPM for 3 days, then 1 mg BID for 3 days, then 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase. | Placebo matched to CP-601,927 1 mg QPM for 3 days, then CP-601,927 1 mg BID for 3 days, and then CP-601,927 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase. |
| Measure Participants | 77 | 85 |
| Week 8 (double-blind baseline) |
26.4
(4.25)
|
26.3
(4.96)
|
| Change at week 9 |
-3.0
(4.49)
|
-3.0
(5.25)
|
| Change at week 10 |
-4.4
(6.57)
|
-4.7
(5.78)
|
| Change at week 11 |
-5.9
(7.40)
|
-6.4
(7.06)
|
| Change at week 12 |
-7.6
(7.63)
|
-6.7
(7.67)
|
| Change at week 13 |
-8.0
(7.22)
|
-7.3
(7.90)
|
| Change at week 14 |
-9.1
(7.76)
|
-8.4
(8.99)
|
| Title | Change From Double-blind Baseline in Bech Melancholia Subscale Score at Weeks 9 Through 14 |
|---|---|
| Description | 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. |
| Time Frame | Weeks 8 (double-blind baseline) through 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The full analysis set, which was defined as the set of all participants who consumed at least one dose of randomized study medication, was applied for the analysis. Number Analyzed = number of participants with evaluable data at each timeframe. |
| Arm/Group Title | CP-601,927 + ADT | Placebo + ADT |
|---|---|---|
| Arm/Group Description | Participants treated with CP-601,927 1 mg QPM for 3 days, then 1 mg BID for 3 days, then 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase. | Placebo matched to CP-601,927 1 mg QPM for 3 days, then CP-601,927 1 mg BID for 3 days, and then CP-601,927 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase. |
| Measure Participants | 77 | 85 |
| Week 8 (double-blind baseline) |
11.6
(1.90)
|
11.6
(2.05)
|
| Change at week 9 |
-1.3
(2.31)
|
-1.5
(2.48)
|
| Change at week 10 |
-2.1
(3.07)
|
-2.0
(2.87)
|
| Change at week 11 |
-3.0
(3.55)
|
-2.7
(3.38)
|
| Change at week 12 |
-3.6
(3.65)
|
-3.0
(3.40)
|
| Change at week 13 |
-3.8
(3.56)
|
-3.2
(3.69)
|
| Change at week 14 |
-4.3
(3.87)
|
-3.7
(4.15)
|
| Title | Change From Double-blind Baseline in Clinical Global Impression - Severity (CGI-S) at Weeks 9, 10, 12, and 14 |
|---|---|
| Description | 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. |
| Time Frame | Week 8 (double-blind baseline) and weeks 9, 10, 12, 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The full analysis set, which was defined as the set of all participants who consumed at least one dose of randomized study medication, was applied for the analysis. Number Analyzed = number of participants with evaluable data at each timeframe. |
| Arm/Group Title | CP-601,927 + ADT | Placebo + ADT |
|---|---|---|
| Arm/Group Description | Participants treated with CP-601,927 1 mg QPM for 3 days, then 1 mg BID for 3 days, then 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase. | Placebo matched to CP-601,927 1 mg QPM for 3 days, then CP-601,927 1 mg BID for 3 days, and then CP-601,927 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase. |
| Measure Participants | 77 | 85 |
| Week 8 (double-blind baseline) |
4.2
(0.59)
|
4.2
(0.67)
|
| Change at week 9 |
-0.2
(0.49)
|
-0.2
(0.60)
|
| Change at week 10 |
-0.5
(0.81)
|
-0.5
(0.83)
|
| Change at week 12 |
-0.8
(1.01)
|
-0.7
(1.14)
|
| Change at week 14 |
-1.1
(1.11)
|
-1.0
(1.18)
|
| Title | Change From Double-blind Baseline in Sheehan Irritability Scale (SIS) Total Score at Weeks 11 and 14 |
|---|---|
| Description | 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. |
| Time Frame | Weeks 8 (double-blind baseline), 11 and 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The full analysis set, which was defined as the set of all participants who consumed at least one dose of randomized study medication, was applied for the analysis. Number Analyzed = number of participants with evaluable data at each timeframe. |
| Arm/Group Title | CP-601,927 + ADT | Placebo + ADT |
|---|---|---|
| Arm/Group Description | Participants treated with CP-601,927 1 mg QPM for 3 days, then 1 mg BID for 3 days, then 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase. | Placebo matched to CP-601,927 1 mg QPM for 3 days, then CP-601,927 1 mg BID for 3 days, and then CP-601,927 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase. |
| Measure Participants | 77 | 85 |
| Week 8 (double-blind baseline) |
36.1
(13.21)
|
34.8
(13.68)
|
| Change at week 11 |
-9.3
(14.41)
|
-7.3
(13.70)
|
| Change at week 14 |
-12.3
(15.80)
|
-10.4
(17.11)
|
| Title | Change From Double-blind Baseline in Sheehan Disability Scale (SDS) Total Score at Weeks 11 and 14 |
|---|---|
| Description | 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). |
| Time Frame | Weeks 8 (double-blind baseline), 11 and 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The full analysis set, which was defined as the set of all participants who consumed at least one dose of randomized study medication, was applied for the analysis. Number Analyzed = number of participants with evaluable data at each timeframe. |
| Arm/Group Title | CP-601,927 + ADT | Placebo + ADT |
|---|---|---|
| Arm/Group Description | Participants treated with CP-601,927 1 mg QPM for 3 days, then 1 mg BID for 3 days, then 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase. | Placebo matched to CP-601,927 1 mg QPM for 3 days, then CP-601,927 1 mg BID for 3 days, and then CP-601,927 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase. |
| Measure Participants | 77 | 85 |
| Week 8 (double-blind baseline) |
19.0
(5.88)
|
18.5
(5.30)
|
| Change at week 11 |
-5.6
(6.98)
|
-3.8
(6.33)
|
| Change at week 14 |
-6.6
(7.98)
|
-5.7
(8.21)
|
| Title | Change From Double-blind Baseline in Sheehan Disability Scale (SDS) Subscale Score at Weeks 11 and 14 |
|---|---|
| Description | 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). |
| Time Frame | Weeks 8 (double-blind baseline), 11 and 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The full analysis set, which was defined as the set of all participants who consumed at least one dose of randomized study medication, was applied for the analysis. Number Analyzed = number of participants with evaluable data at each timeframe. |
| Arm/Group Title | CP-601,927 + ADT | Placebo + ADT |
|---|---|---|
| Arm/Group Description | Participants treated with CP-601,927 1 mg QPM for 3 days, then 1 mg BID for 3 days, then 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase. | Placebo matched to CP-601,927 1 mg QPM for 3 days, then CP-601,927 1 mg BID for 3 days, and then CP-601,927 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase. |
| Measure Participants | 77 | 85 |
| Week 8 (double-blind baseline) |
6.0
(2.22)
|
5.5
(2.66)
|
| Change at week 11 |
-2.1
(2.86)
|
-0.9
(2.10)
|
| Change at week 14 |
-2.1
(2.88)
|
-1.9
(2.66)
|
| Title | Clinical Global Impression - Improvement (CGI-I) Total Score at Weeks 9, 10, 12 and 14 |
|---|---|
| Description | 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. |
| Time Frame | Weeks 8 (double-blind baseline) 9, 10, 12 and 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The full analysis set, which was defined as the set of all participants who consumed at least one dose of randomized study medication, was applied for the analysis. Number Analyzed = number of participants with evaluable data at each timeframe. |
| Arm/Group Title | CP-601,927 + ADT | Placebo + ADT |
|---|---|---|
| Arm/Group Description | Participants treated with CP-601,927 1 mg QPM for 3 days, then 1 mg BID for 3 days, then 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase. | Placebo matched to CP-601,927 1 mg QPM for 3 days, then CP-601,927 1 mg BID for 3 days, and then CP-601,927 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase. |
| Measure Participants | 77 | 85 |
| Week 8 (double-blind baseline) |
3.7
(0.77)
|
3.5
(0.66)
|
| Week 9 |
3.4
(0.84)
|
3.2
(0.78)
|
| Week 10 |
3.2
(0.92)
|
3.1
(0.88)
|
| Week 12 |
2.7
(1.05)
|
2.8
(1.07)
|
| Week 14 |
2.5
(1.05)
|
2.7
(1.03)
|
| Title | Number of Participants With Remission at Weeks 9, 10, 12 and 14 |
|---|---|
| Description | 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). |
| Time Frame | Weeks 9, 10, 12 and 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The full analysis set, which was defined as the set of all participants who consumed at least one dose of randomized study medication, was applied for the analysis. Number Analyzed = number of participants with evaluable data at each timeframe. |
| Arm/Group Title | CP-601,927 + ADT | Placebo + ADT |
|---|---|---|
| Arm/Group Description | Participants treated with CP-601,927 1 mg QPM for 3 days, then 1 mg BID for 3 days, then 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase. | Placebo matched to CP-601,927 1 mg QPM for 3 days, then CP-601,927 1 mg BID for 3 days, and then CP-601,927 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase. |
| Measure Participants | 76 | 82 |
| Week 9 |
1
0.3%
|
0
NaN
|
| Week 10 |
4
1.3%
|
1
NaN
|
| Week 12 |
5
1.7%
|
9
NaN
|
| Week 14 |
9
3%
|
11
NaN
|
| Title | Number of Participants With Response at Weeks 9 Through 14 |
|---|---|
| Description | Response was defined as greater than 50 percent reduction from double-blind baseline in MADRS total score. |
| Time Frame | Weeks 9 through 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The full analysis set, which was defined as the set of all participants who consumed at least one dose of randomized study medication, was applied for the analysis. Number Analyzed = number of participants with evaluable data at each timeframe. |
| Arm/Group Title | CP-601,927 + ADT | Placebo + ADT |
|---|---|---|
| Arm/Group Description | Participants treated with CP-601,927 1 mg QPM for 3 days, then 1 mg BID for 3 days, then 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase. | Placebo matched to CP-601,927 1 mg QPM for 3 days, then CP-601,927 1 mg BID for 3 days, and then CP-601,927 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase. |
| Measure Participants | 76 | 82 |
| Week 9 |
3
1%
|
4
NaN
|
| Week 10 |
8
2.7%
|
8
NaN
|
| Week 11 |
15
5.1%
|
10
NaN
|
| Week 12 |
18
6.1%
|
16
NaN
|
| Week 13 |
23
7.7%
|
20
NaN
|
| Week 14 |
22
7.4%
|
20
NaN
|
| Title | Population Pharmacokinetics |
|---|---|
| Description | 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 |
| Time Frame | Weeks 11,12 and 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Plasma CP-601,927 Concentration |
|---|---|
| Description | Blood samples were collected for plasma CP-601,927 concentration analysis which was summarized by mean and standard deviation. |
| Time Frame | Week 11, 12 and 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants with at least one dose of study medication in DB (double blind) phase and one valid plasma concentration measurement collected during the DB phase was be included in the analyses of the PK endpoints. Number Analyzed = number of participants with evaluable data at each timeframe. |
| Arm/Group Title | CP-601,927 + ADT |
|---|---|
| Arm/Group Description | Participants treated with CP-601,927 1 mg QPM for 3 days, then 1 mg BID for 3 days, then 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase. |
| Measure Participants | 60 |
| Week 11 at 1 Hour |
5.80
(3.42)
|
| Week 11 at 2 Hours |
5.90
(3.13)
|
| Week 12 |
6.24
(3.85)
|
| Week 14 at 1 Hour |
5.36
(3.83)
|
| Week 14 at 2 Hour |
5.39
(3.89)
|
| Title | The Sheehan Suicidality Tracking Scale (STS) |
|---|---|
| Description | 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. |
| Time Frame | Week 8 (double-blind baseline) and weeks 9 through 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The full analysis set, which was defined as the set of all participants who consumed at least one dose of randomized study medication, was applied for the analysis. Number Analyzed = number of participants with evaluable data at each timeframe. |
| Arm/Group Title | CP-601,927 + ADT | Placebo + ADT |
|---|---|---|
| Arm/Group Description | Participants treated with CP-601,927 1 mg QPM for 3 days, then 1 mg BID for 3 days, then 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase. | Placebo matched to CP-601,927 1 mg QPM for 3 days, then CP-601,927 1 mg BID for 3 days, and then CP-601,927 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase. |
| Measure Participants | 77 | 85 |
| Week 8: suicidal ideation |
11
3.7%
|
13
NaN
|
| Week 8: no suicidal behavior and risk |
66
22.2%
|
72
NaN
|
| Week 9: suicidal ideation |
10
3.4%
|
8
NaN
|
| Week 9: self-injurious, no intent |
1
0.3%
|
0
NaN
|
| Week 9: no suicidal behavior and risk |
61
20.5%
|
71
NaN
|
| Week 10: suicidal ideation |
12
4%
|
7
NaN
|
| Week 10: no suicidal behavior and risk |
57
19.2%
|
67
NaN
|
| Week 11: suicidal ideation |
8
2.7%
|
5
NaN
|
| Week 11: no suicidal behavior and risk |
56
18.9%
|
66
NaN
|
| Week 12: suicidal ideation |
6
2%
|
5
NaN
|
| Week 12: no suicidal behavior and risk |
57
19.2%
|
65
NaN
|
| Week 13: suicidal ideation |
5
1.7%
|
5
NaN
|
| Week 13: no suicidal behavior and risk |
57
19.2%
|
58
NaN
|
| Week 14: suicidal ideation |
5
1.7%
|
6
NaN
|
| Week 14: no suicidal behavior and risk |
70
23.6%
|
75
NaN
|
Adverse Events
| Time Frame | ||||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. | |||||
| Arm/Group Title | Open-Label ADT | CP-601,927 + ADT | Placebo + ADT | |||
| Arm/Group Description | Participants treated with 1 of 5 allowed antidepressant agents in accordance with current product labeling, targeting the following doses by the end of week 2: escitalopram (Lexapro) (10-20 mg/d), citalopram (Celexa) (20-40 mg/d), fluoxetine (Prozac, Sarafem) (20-60 mg/d), paroxetine CR (Paxil CR) (37.5-62.5 mg/d), sertraline (Zoloft) (100-200 mg/d), for up to 8 weeks in open-label phase. | Participants treated with CP-601,927 1 mg QPM for 3 days, then 1 mg BID for 3 days, then 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase. | Placebo matched to CP-601,927 1 mg QPM for 3 days, then CP-601,927 1 mg BID for 3 days, and then CP-601,927 2 mg BID on Day 7 of dosing in the double-blind phase. Dose in participants experiencing intolerable nausea may be reduced to 1 mg BID for 6 weeks and a 7-10 day follow-up period. Background ADT (continued from Open-Label ADT) was applied in the double-blind phase. | |||
All Cause Mortality |
||||||
| Open-Label ADT | CP-601,927 + ADT | Placebo + ADT | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| Open-Label ADT | CP-601,927 + ADT | Placebo + ADT | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/297 (1%) | 1/77 (1.3%) | 1/85 (1.2%) | |||
| Cardiac disorders | ||||||
| Atrial fibrillation | 1/297 (0.3%) | 0/77 (0%) | 0/85 (0%) | |||
| Infections and infestations | ||||||
| Pneumonia | 1/297 (0.3%) | 0/77 (0%) | 0/85 (0%) | |||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Thyroid cancer | 0/297 (0%) | 1/77 (1.3%) | 0/85 (0%) | |||
| Pregnancy, puerperium and perinatal conditions | ||||||
| Pregnancy | 1/297 (0.3%) | 0/77 (0%) | 0/85 (0%) | |||
| Psychiatric disorders | ||||||
| Suicide attempt | 0/297 (0%) | 0/77 (0%) | 1/85 (1.2%) | |||
| Suicidal ideation | 1/297 (0.3%) | 0/77 (0%) | 0/85 (0%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| Open-Label ADT | CP-601,927 + ADT | Placebo + ADT | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 210/297 (70.7%) | 58/77 (75.3%) | 61/85 (71.8%) | |||
| Cardiac disorders | ||||||
| Palpitations | 4/297 (1.3%) | 1/77 (1.3%) | 0/85 (0%) | |||
| Tachycardia | 1/297 (0.3%) | 0/77 (0%) | 0/85 (0%) | |||
| Ear and labyrinth disorders | ||||||
| Cerumen impaction | 0/297 (0%) | 0/77 (0%) | 1/85 (1.2%) | |||
| Ear pain | 1/297 (0.3%) | 0/77 (0%) | 0/85 (0%) | |||
| Tinnitus | 1/297 (0.3%) | 0/77 (0%) | 0/85 (0%) | |||
| Vertigo | 0/297 (0%) | 0/77 (0%) | 1/85 (1.2%) | |||
| Eye disorders | ||||||
| Conjunctivitis | 1/297 (0.3%) | 0/77 (0%) | 0/85 (0%) | |||
| Vision blurred | 2/297 (0.7%) | 0/77 (0%) | 1/85 (1.2%) | |||
| Visual impairment | 1/297 (0.3%) | 0/77 (0%) | 0/85 (0%) | |||
| Gastrointestinal disorders | ||||||
| Abdominal discomfort | 5/297 (1.7%) | 3/77 (3.9%) | 0/85 (0%) | |||
| Abdominal distension | 2/297 (0.7%) | 0/77 (0%) | 0/85 (0%) | |||
| Abdominal pain | 3/297 (1%) | 1/77 (1.3%) | 1/85 (1.2%) | |||
| Abdominal pain lower | 0/297 (0%) | 1/77 (1.3%) | 0/85 (0%) | |||
| Abdominal pain upper | 6/297 (2%) | 4/77 (5.2%) | 1/85 (1.2%) | |||
| Abdominal tenderness | 1/297 (0.3%) | 0/77 (0%) | 0/85 (0%) | |||
| Constipation | 11/297 (3.7%) | 2/77 (2.6%) | 3/85 (3.5%) | |||
| Dental caries | 0/297 (0%) | 0/77 (0%) | 1/85 (1.2%) | |||
| Diarrhoea | 28/297 (9.4%) | 4/77 (5.2%) | 5/85 (5.9%) | |||
| Dry mouth | 17/297 (5.7%) | 4/77 (5.2%) | 8/85 (9.4%) | |||
| Dyspepsia | 6/297 (2%) | 3/77 (3.9%) | 1/85 (1.2%) | |||
| Dysphagia | 1/297 (0.3%) | 1/77 (1.3%) | 0/85 (0%) | |||
| Eructation | 1/297 (0.3%) | 0/77 (0%) | 0/85 (0%) | |||
| Faeces discoloured | 1/297 (0.3%) | 0/77 (0%) | 0/85 (0%) | |||
| Flatulence | 7/297 (2.4%) | 1/77 (1.3%) | 0/85 (0%) | |||
| Gastrointestinal disorder | 1/297 (0.3%) | 0/77 (0%) | 0/85 (0%) | |||
| Gastrointestinal pain | 2/297 (0.7%) | 0/77 (0%) | 1/85 (1.2%) | |||
| Gastrointestinal sounds abnormal | 0/297 (0%) | 1/77 (1.3%) | 0/85 (0%) | |||
| Gastrooesophageal reflux disease | 3/297 (1%) | 1/77 (1.3%) | 0/85 (0%) | |||
| Gingival swelling | 1/297 (0.3%) | 0/77 (0%) | 0/85 (0%) | |||
| Haemorrhoids | 1/297 (0.3%) | 0/77 (0%) | 0/85 (0%) | |||
| Hiatus hernia | 1/297 (0.3%) | 0/77 (0%) | 1/85 (1.2%) | |||
| Nausea | 39/297 (13.1%) | 11/77 (14.3%) | 12/85 (14.1%) | |||
| Oesophageal obstruction | 1/297 (0.3%) | 0/77 (0%) | 0/85 (0%) | |||
| Rectal haemorrhage | 0/297 (0%) | 0/77 (0%) | 1/85 (1.2%) | |||
| Tongue cyst | 1/297 (0.3%) | 0/77 (0%) | 1/85 (1.2%) | |||
| Toothache | 3/297 (1%) | 0/77 (0%) | 2/85 (2.4%) | |||
| Vomiting | 3/297 (1%) | 2/77 (2.6%) | 1/85 (1.2%) | |||
| General disorders | ||||||
| Asthenia | 2/297 (0.7%) | 1/77 (1.3%) | 1/85 (1.2%) | |||
| Chills | 1/297 (0.3%) | 0/77 (0%) | 0/85 (0%) | |||
| Drug withdrawal syndrome | 1/297 (0.3%) | 0/77 (0%) | 0/85 (0%) | |||
| Fatigue | 18/297 (6.1%) | 3/77 (3.9%) | 13/85 (15.3%) | |||
| Feeling abnormal | 0/297 (0%) | 1/77 (1.3%) | 0/85 (0%) | |||
| Feeling hot | 1/297 (0.3%) | 0/77 (0%) | 1/85 (1.2%) | |||
| Feeling jittery | 3/297 (1%) | 1/77 (1.3%) | 0/85 (0%) | |||
| Influenza like illness | 1/297 (0.3%) | 0/77 (0%) | 0/85 (0%) | |||
| Irritability | 12/297 (4%) | 2/77 (2.6%) | 5/85 (5.9%) | |||
| Local swelling | 1/297 (0.3%) | 0/77 (0%) | 0/85 (0%) | |||
| Oedema peripheral | 4/297 (1.3%) | 1/77 (1.3%) | 0/85 (0%) | |||
| Pain | 2/297 (0.7%) | 1/77 (1.3%) | 0/85 (0%) | |||
| Pyrexia | 4/297 (1.3%) | 0/77 (0%) | 0/85 (0%) | |||
| Thirst | 1/297 (0.3%) | 0/77 (0%) | 0/85 (0%) | |||
| Hepatobiliary disorders | ||||||
| Biliary colic | 1/297 (0.3%) | 1/77 (1.3%) | 0/85 (0%) | |||
| Immune system disorders | ||||||
| Hypersensitivity | 1/297 (0.3%) | 1/77 (1.3%) | 0/85 (0%) | |||
| Multiple allergies | 1/297 (0.3%) | 0/77 (0%) | 0/85 (0%) | |||
| Seasonal allergy | 0/297 (0%) | 1/77 (1.3%) | 0/85 (0%) | |||
| Infections and infestations | ||||||
| Abscess limb | 1/297 (0.3%) | 0/77 (0%) | 0/85 (0%) | |||
| Bronchitis | 2/297 (0.7%) | 0/77 (0%) | 1/85 (1.2%) | |||
| Cellulitis staphylococcal | 1/297 (0.3%) | 0/77 (0%) | 0/85 (0%) | |||
| Conjunctivitis infective | 1/297 (0.3%) | 0/77 (0%) | 1/85 (1.2%) | |||
| Fungal infection | 1/297 (0.3%) | 0/77 (0%) | 1/85 (1.2%) | |||
| Gastroenteritis | 2/297 (0.7%) | 0/77 (0%) | 1/85 (1.2%) | |||
| Gastroenteritis viral | 2/297 (0.7%) | 0/77 (0%) | 0/85 (0%) | |||
| Gastrointestinal viral infection | 1/297 (0.3%) | 1/77 (1.3%) | 0/85 (0%) | |||
| Gingival infection | 0/297 (0%) | 0/77 (0%) | 1/85 (1.2%) | |||
| Herpes simplex | 0/297 (0%) | 1/77 (1.3%) | 0/85 (0%) | |||
| Influenza | 6/297 (2%) | 1/77 (1.3%) | 2/85 (2.4%) | |||
| Laryngitis | 0/297 (0%) | 1/77 (1.3%) | 0/85 (0%) | |||
| Nasopharyngitis | 10/297 (3.4%) | 2/77 (2.6%) | 2/85 (2.4%) | |||
| Oral infection | 0/297 (0%) | 1/77 (1.3%) | 0/85 (0%) | |||
| Pharyngitis streptococcal | 1/297 (0.3%) | 0/77 (0%) | 0/85 (0%) | |||
| Pneumonia | 1/297 (0.3%) | 0/77 (0%) | 0/85 (0%) | |||
| Respiratory tract infection | 1/297 (0.3%) | 0/77 (0%) | 0/85 (0%) | |||
| Sinusitis | 5/297 (1.7%) | 1/77 (1.3%) | 2/85 (2.4%) | |||
| Tooth abscess | 0/297 (0%) | 0/77 (0%) | 1/85 (1.2%) | |||
| Tooth infection | 1/297 (0.3%) | 1/77 (1.3%) | 0/85 (0%) | |||
| Upper respiratory tract infection | 24/297 (8.1%) | 6/77 (7.8%) | 4/85 (4.7%) | |||
| Urinary tract infection | 6/297 (2%) | 4/77 (5.2%) | 2/85 (2.4%) | |||
| Viral infection | 1/297 (0.3%) | 0/77 (0%) | 0/85 (0%) | |||
| Vulvovaginal candidiasis | 1/297 (0.3%) | 0/77 (0%) | 0/85 (0%) | |||
| Injury, poisoning and procedural complications | ||||||
| Alcohol poisoning | 1/297 (0.3%) | 0/77 (0%) | 0/85 (0%) | |||
| Arthropod bite | 2/297 (0.7%) | 0/77 (0%) | 0/85 (0%) | |||
| Contusion | 3/297 (1%) | 0/77 (0%) | 1/85 (1.2%) | |||
| Excoriation | 1/297 (0.3%) | 1/77 (1.3%) | 0/85 (0%) | |||
| Fall | 1/297 (0.3%) | 2/77 (2.6%) | 1/85 (1.2%) | |||
| Foot fracture | 1/297 (0.3%) | 0/77 (0%) | 0/85 (0%) | |||
| Fractured coccyx | 1/297 (0.3%) | 0/77 (0%) | 0/85 (0%) | |||
| Fractured sacrum | 1/297 (0.3%) | 0/77 (0%) | 0/85 (0%) | |||
| Hand fracture | 1/297 (0.3%) | 0/77 (0%) | 1/85 (1.2%) | |||
| Laceration | 3/297 (1%) | 0/77 (0%) | 1/85 (1.2%) | |||
| Ligament sprain | 0/297 (0%) | 1/77 (1.3%) | 0/85 (0%) | |||
| Meniscus lesion | 1/297 (0.3%) | 1/77 (1.3%) | 0/85 (0%) | |||
| Muscle strain | 0/297 (0%) | 1/77 (1.3%) | 0/85 (0%) | |||
| Overdose | 1/297 (0.3%) | 0/77 (0%) | 0/85 (0%) | |||
| Investigations | ||||||
| Alanine aminotransferase increased | 0/297 (0%) | 1/77 (1.3%) | 0/85 (0%) | |||
| Blood creatine phosphokinase increased | 1/297 (0.3%) | 0/77 (0%) | 1/85 (1.2%) | |||
| Blood glucose decreased | 1/297 (0.3%) | 0/77 (0%) | 0/85 (0%) | |||
| Blood glucose increased | 0/297 (0%) | 1/77 (1.3%) | 0/85 (0%) | |||
| Blood pressure increased | 2/297 (0.7%) | 1/77 (1.3%) | 3/85 (3.5%) | |||
| Colonoscopy | 1/297 (0.3%) | 0/77 (0%) | 0/85 (0%) | |||
| Electrocardiogram QT prolonged | 0/297 (0%) | 0/77 (0%) | 1/85 (1.2%) | |||
| Gamma-glutamyltransferase | 0/297 (0%) | 1/77 (1.3%) | 0/85 (0%) | |||
| Gamma-glutamyltransferase increased | 1/297 (0.3%) | 0/77 (0%) | 0/85 (0%) | |||
| Liver function test abnormal | 1/297 (0.3%) | 0/77 (0%) | 1/85 (1.2%) | |||
| Positive Rombergism | 0/297 (0%) | 1/77 (1.3%) | 0/85 (0%) | |||
| Vitamin D decreased | 0/297 (0%) | 0/77 (0%) | 1/85 (1.2%) | |||
| Weight decreased | 1/297 (0.3%) | 2/77 (2.6%) | 0/85 (0%) | |||
| Weight increased | 0/297 (0%) | 1/77 (1.3%) | 1/85 (1.2%) | |||
| Metabolism and nutrition disorders | ||||||
| Decreased appetite | 5/297 (1.7%) | 3/77 (3.9%) | 1/85 (1.2%) | |||
| Dehydration | 1/297 (0.3%) | 0/77 (0%) | 0/85 (0%) | |||
| Food craving | 2/297 (0.7%) | 0/77 (0%) | 1/85 (1.2%) | |||
| Hyponatraemia | 1/297 (0.3%) | 0/77 (0%) | 0/85 (0%) | |||
| Increased appetite | 4/297 (1.3%) | 1/77 (1.3%) | 3/85 (3.5%) | |||
| Vitamin D deficiency | 1/297 (0.3%) | 0/77 (0%) | 0/85 (0%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 3/297 (1%) | 1/77 (1.3%) | 2/85 (2.4%) | |||
| Back pain | 3/297 (1%) | 1/77 (1.3%) | 5/85 (5.9%) | |||
| Flank pain | 2/297 (0.7%) | 1/77 (1.3%) | 0/85 (0%) | |||
| Muscle disorder | 0/297 (0%) | 0/77 (0%) | 1/85 (1.2%) | |||
| Muscle spasms | 1/297 (0.3%) | 2/77 (2.6%) | 1/85 (1.2%) | |||
| Muscle tightness | 1/297 (0.3%) | 0/77 (0%) | 0/85 (0%) | |||
| Muscle twitching | 2/297 (0.7%) | 2/77 (2.6%) | 0/85 (0%) | |||
| Musculoskeletal chest pain | 0/297 (0%) | 0/77 (0%) | 1/85 (1.2%) | |||
| Musculoskeletal pain | 2/297 (0.7%) | 0/77 (0%) | 2/85 (2.4%) | |||
| Musculoskeletal stiffness | 3/297 (1%) | 0/77 (0%) | 0/85 (0%) | |||
| Myalgia | 4/297 (1.3%) | 2/77 (2.6%) | 1/85 (1.2%) | |||
| Neck pain | 2/297 (0.7%) | 0/77 (0%) | 1/85 (1.2%) | |||
| Pain in extremity | 3/297 (1%) | 1/77 (1.3%) | 0/85 (0%) | |||
| Pain in jaw | 0/297 (0%) | 0/77 (0%) | 1/85 (1.2%) | |||
| Spondylitis | 1/297 (0.3%) | 0/77 (0%) | 1/85 (1.2%) | |||
| Nervous system disorders | ||||||
| Akathisia | 1/297 (0.3%) | 0/77 (0%) | 0/85 (0%) | |||
| Amnesia | 1/297 (0.3%) | 1/77 (1.3%) | 0/85 (0%) | |||
| Aphasia | 0/297 (0%) | 0/77 (0%) | 1/85 (1.2%) | |||
| Cognitive disorder | 0/297 (0%) | 0/77 (0%) | 1/85 (1.2%) | |||
| Disturbance in attention | 1/297 (0.3%) | 0/77 (0%) | 1/85 (1.2%) | |||
| Dizziness | 22/297 (7.4%) | 5/77 (6.5%) | 4/85 (4.7%) | |||
| Dysgeusia | 0/297 (0%) | 0/77 (0%) | 1/85 (1.2%) | |||
| Dyskinesia | 1/297 (0.3%) | 0/77 (0%) | 0/85 (0%) | |||
| Headache | 42/297 (14.1%) | 16/77 (20.8%) | 12/85 (14.1%) | |||
| Hypersomnia | 1/297 (0.3%) | 0/77 (0%) | 0/85 (0%) | |||
| Hypoaesthesia | 1/297 (0.3%) | 1/77 (1.3%) | 0/85 (0%) | |||
| Lethargy | 2/297 (0.7%) | 1/77 (1.3%) | 1/85 (1.2%) | |||
| Memory impairment | 2/297 (0.7%) | 0/77 (0%) | 1/85 (1.2%) | |||
| Migraine | 1/297 (0.3%) | 1/77 (1.3%) | 0/85 (0%) | |||
| Neuralgia | 1/297 (0.3%) | 0/77 (0%) | 0/85 (0%) | |||
| Oromandibular dystonia | 1/297 (0.3%) | 0/77 (0%) | 0/85 (0%) | |||
| Paraesthesia | 4/297 (1.3%) | 1/77 (1.3%) | 0/85 (0%) | |||
| Poor quality sleep | 2/297 (0.7%) | 0/77 (0%) | 0/85 (0%) | |||
| Psychomotor hyperactivity | 0/297 (0%) | 1/77 (1.3%) | 0/85 (0%) | |||
| Restless legs syndrome | 2/297 (0.7%) | 0/77 (0%) | 1/85 (1.2%) | |||
| Retrograde amnesia | 1/297 (0.3%) | 0/77 (0%) | 0/85 (0%) | |||
| Sedation | 6/297 (2%) | 1/77 (1.3%) | 1/85 (1.2%) | |||
| Sinus headache | 1/297 (0.3%) | 0/77 (0%) | 0/85 (0%) | |||
| Somnolence | 18/297 (6.1%) | 4/77 (5.2%) | 4/85 (4.7%) | |||
| Syncope | 0/297 (0%) | 1/77 (1.3%) | 0/85 (0%) | |||
| Tension headache | 0/297 (0%) | 1/77 (1.3%) | 0/85 (0%) | |||
| Tremor | 3/297 (1%) | 2/77 (2.6%) | 0/85 (0%) | |||
| Psychiatric disorders | ||||||
| Abnormal dreams | 3/297 (1%) | 5/77 (6.5%) | 3/85 (3.5%) | |||
| Affective disorder | 1/297 (0.3%) | 0/77 (0%) | 0/85 (0%) | |||
| Agitation | 2/297 (0.7%) | 0/77 (0%) | 1/85 (1.2%) | |||
| Anger | 0/297 (0%) | 0/77 (0%) | 1/85 (1.2%) | |||
| Anorgasmia | 1/297 (0.3%) | 0/77 (0%) | 0/85 (0%) | |||
| Anxiety | 8/297 (2.7%) | 2/77 (2.6%) | 1/85 (1.2%) | |||
| Apathy | 2/297 (0.7%) | 0/77 (0%) | 1/85 (1.2%) | |||
| Bruxism | 3/297 (1%) | 0/77 (0%) | 1/85 (1.2%) | |||
| Depression | 4/297 (1.3%) | 0/77 (0%) | 1/85 (1.2%) | |||
| Emotional disorder | 1/297 (0.3%) | 0/77 (0%) | 1/85 (1.2%) | |||
| Initial insomnia | 3/297 (1%) | 1/77 (1.3%) | 1/85 (1.2%) | |||
| Insomnia | 24/297 (8.1%) | 10/77 (13%) | 10/85 (11.8%) | |||
| Libido decreased | 7/297 (2.4%) | 1/77 (1.3%) | 2/85 (2.4%) | |||
| Mental status changes | 1/297 (0.3%) | 0/77 (0%) | 0/85 (0%) | |||
| Middle insomnia | 0/297 (0%) | 0/77 (0%) | 1/85 (1.2%) | |||
| Nervousness | 2/297 (0.7%) | 1/77 (1.3%) | 0/85 (0%) | |||
| Nightmare | 0/297 (0%) | 3/77 (3.9%) | 2/85 (2.4%) | |||
| Orgasm abnormal | 1/297 (0.3%) | 0/77 (0%) | 1/85 (1.2%) | |||
| Panic attack | 0/297 (0%) | 0/77 (0%) | 1/85 (1.2%) | |||
| Panic reaction | 0/297 (0%) | 1/77 (1.3%) | 0/85 (0%) | |||
| Paranoia | 2/297 (0.7%) | 0/77 (0%) | 0/85 (0%) | |||
| Personality disorder | 0/297 (0%) | 1/77 (1.3%) | 0/85 (0%) | |||
| Restlessness | 1/297 (0.3%) | 0/77 (0%) | 0/85 (0%) | |||
| Sleep disorder | 1/297 (0.3%) | 0/77 (0%) | 0/85 (0%) | |||
| Sleep terror | 0/297 (0%) | 1/77 (1.3%) | 0/85 (0%) | |||
| Suspiciousness | 1/297 (0.3%) | 0/77 (0%) | 1/85 (1.2%) | |||
| Tachyphrenia | 0/297 (0%) | 1/77 (1.3%) | 0/85 (0%) | |||
| Terminal insomnia | 1/297 (0.3%) | 0/77 (0%) | 0/85 (0%) | |||
| Renal and urinary disorders | ||||||
| Dysuria | 0/297 (0%) | 0/77 (0%) | 1/85 (1.2%) | |||
| Micturition urgency | 1/297 (0.3%) | 1/77 (1.3%) | 0/85 (0%) | |||
| Pollakiuria | 1/297 (0.3%) | 1/77 (1.3%) | 0/85 (0%) | |||
| Reproductive system and breast disorders | ||||||
| Ejaculation delayed | 1/297 (0.3%) | 1/77 (1.3%) | 0/85 (0%) | |||
| Erection increased | 1/297 (0.3%) | 0/77 (0%) | 0/85 (0%) | |||
| Menstruation delayed | 0/297 (0%) | 0/77 (0%) | 1/85 (1.2%) | |||
| Polycystic ovaries | 0/297 (0%) | 1/77 (1.3%) | 0/85 (0%) | |||
| Polymenorrhoea | 1/297 (0.3%) | 0/77 (0%) | 1/85 (1.2%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Asthma | 1/297 (0.3%) | 0/77 (0%) | 0/85 (0%) | |||
| Cough | 0/297 (0%) | 1/77 (1.3%) | 0/85 (0%) | |||
| Dry throat | 1/297 (0.3%) | 0/77 (0%) | 0/85 (0%) | |||
| Dyspnoea | 1/297 (0.3%) | 1/77 (1.3%) | 0/85 (0%) | |||
| Epistaxis | 1/297 (0.3%) | 0/77 (0%) | 0/85 (0%) | |||
| Nasal congestion | 1/297 (0.3%) | 2/77 (2.6%) | 1/85 (1.2%) | |||
| Oropharyngeal pain | 7/297 (2.4%) | 0/77 (0%) | 0/85 (0%) | |||
| Respiratory tract congestion | 0/297 (0%) | 0/77 (0%) | 1/85 (1.2%) | |||
| Rhinitis allergic | 1/297 (0.3%) | 0/77 (0%) | 0/85 (0%) | |||
| Sinus congestion | 1/297 (0.3%) | 1/77 (1.3%) | 0/85 (0%) | |||
| Yawning | 3/297 (1%) | 2/77 (2.6%) | 0/85 (0%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Acne | 1/297 (0.3%) | 2/77 (2.6%) | 0/85 (0%) | |||
| Dermatitis | 1/297 (0.3%) | 0/77 (0%) | 0/85 (0%) | |||
| Hyperhidrosis | 5/297 (1.7%) | 0/77 (0%) | 1/85 (1.2%) | |||
| Nail discolouration | 1/297 (0.3%) | 0/77 (0%) | 0/85 (0%) | |||
| Night sweats | 0/297 (0%) | 0/77 (0%) | 1/85 (1.2%) | |||
| Pruritus | 3/297 (1%) | 2/77 (2.6%) | 0/85 (0%) | |||
| Rash | 1/297 (0.3%) | 1/77 (1.3%) | 1/85 (1.2%) | |||
| Urticaria | 1/297 (0.3%) | 1/77 (1.3%) | 0/85 (0%) | |||
| Surgical and medical procedures | ||||||
| Colon polypectomy | 1/297 (0.3%) | 0/77 (0%) | 0/85 (0%) | |||
| Vascular disorders | ||||||
| Flushing | 1/297 (0.3%) | 0/77 (0%) | 0/85 (0%) | |||
| Haematoma | 0/297 (0%) | 1/77 (1.3%) | 0/85 (0%) | |||
| Hot flush | 4/297 (1.3%) | 0/77 (0%) | 1/85 (1.2%) | |||
| Hypertension | 2/297 (0.7%) | 3/77 (3.9%) | 0/85 (0%) | |||
| Hypotension | 2/297 (0.7%) | 2/77 (2.6%) | 0/85 (0%) | |||
| Orthostatic hypotension | 0/297 (0%) | 1/77 (1.3%) | 0/85 (0%) | |||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
| Name/Title | Pfizer ClinicalTrials.gov Call Center |
|---|---|
| Organization | Pfizer, Inc. |
| Phone | 1-800-718-1021 |
| ClinicalTrials.gov_Inquiries@pfizer.com |
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT01098240
Other Study ID Numbers:
- A3331017
First Posted:
Apr 2, 2010
Last Update Posted:
May 3, 2021
Last Verified:
Apr 1, 2021