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Randomized, Double-Blind, Placebo Controlled Study of Vilazodone's Efficacy, Safety, and Biomarkers of Response in Major Depressive Disorder (MDD)

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ClinicalTrials.gov Identifier: NCT00683592
Recruitment Status : Completed
First Posted : May 23, 2008
Results First Posted : October 27, 2010
Last Update Posted : October 27, 2010
Sponsor:
Information provided by:
Forest Laboratories

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Major Depressive Disorder
Interventions Drug: vilazodone
Drug: placebo
Enrollment 481

Recruitment Details Recruitment period was 31Mar2008 to 10Feb2009.
Pre-assignment Details This study included a washout period to allow patients to discontinue their current antidepressant medications and any additional medications prohibited by the protocol, if applicable.
Arm/Group Title Vilazodone Placebo
Hide Arm/Group Description Vilazodone titrated to 40mg. Two tablets per day. Placebo to match vilazodone. Two tablets per day.
Period Title: Overall Study
Started 240 241
Intent to Treat Population 231 232
Safety Population 235 233
Completed 193 195
Not Completed 47 46
Reason Not Completed
Adverse Event             12             4
Withdrawal by Subject             11             11
Lost to Follow-up             17             17
Lack of Efficacy             3             7
Physician Decision             0             1
Non-compliance             3             5
Other             1             1
Arm/Group Title Vilazodone (ITT Population) Placebo (ITT Population) Total
Hide Arm/Group Description Vilazodone, 40 mg placebo to match vilazodone Total of all reporting groups
Overall Number of Baseline Participants 231 232 463
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 231 participants 232 participants 463 participants
41.1  (12.22) 42.4  (12.49) 41.7  (12.36)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 231 participants 232 participants 463 participants
Female
138
  59.7%
123
  53.0%
261
  56.4%
Male
93
  40.3%
109
  47.0%
202
  43.6%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 231 participants 232 participants 463 participants
231 232 463
1.Primary Outcome
Title Change From Baseline to Week 8 in the MADRS (Montgomery-Asberg Depression Rating Scale) Total Score.
Hide Description The MADRS is an observer rating scale that has proven to be an efficient and practical measure of depression. The scale was constructed to be sensitive to treatment effects. The change from baseline in MADRS total score has a possible range of -60 to 60 where negative values reflect improvement in depression symptom severity. The method of last observation carried forward was utilized for subjects who discontinued prematurely.
Time Frame Baseline, Week 1, Week 2, Week 4, Week 6, Week 8
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT): the ITT population consisted of patients who were randomized, took at least 1 dose of study drug, and had at least 1 post-baseline efficacy endpoint measurement.
Arm/Group Title Vilazodone (ITT Population) Placebo (ITT Population)
Hide Arm/Group Description:
Vilazodone, 40 mg
placebo to match vilazodone
Overall Number of Participants Analyzed 231 231
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Units on a scale
-13.3
(-15.1 to -11.5)
-10.8
(-12.6 to -9.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vilazodone (ITT Population), Placebo (ITT Population)
Comments The model was an analysis of covariance (ANCOVA), with terms for treatment group and center, adjusting for baseline MADRS total score. Missing values at week 8 were handled using the last observation carried forward (LOCF) approach.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.009
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Least Squares Mean Change
Estimated Value -2.5
Confidence Interval (2-Sided) 95%
-4.4 to -0.6
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline to Week 8 in the HAM-D 17 (17-Item Hamilton Rating Scale for Depression) Total Score
Hide Description The HAM-D 17 is a 17-item subscale of the HAM-D 21, which is designed to be completed by a trained rater. It is designed for rating depressive symptom severity in patients with a confirmed diagnosis of depressive disorder. The change in HAM-D 17 has a possible range of -52 to 52 with negative values indicating improvment in depression symptom severity. The method of last observation carried forward was utilized for subjects who discontinued prematurely.
Time Frame Baseline, week 1, week 2, week 4, week 6, week 8
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT): the ITT population consisted of patients who were randomized, took at least 1 dose of study drug, and had at least 1 post-baseline efficacy endpoint measurement.
Arm/Group Title Vilazodone (ITT Population) Placebo (ITT Population)
Hide Arm/Group Description:
Vilazodone, 40 mg
placebo to match vilazodone
Overall Number of Participants Analyzed 231 231
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Units on a scale
-10.7
(-12.1 to -9.4)
-9.1
(-10.4 to -7.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vilazodone (ITT Population), Placebo (ITT Population)
Comments The model was an analysis of covariance (ANCOVA), with terms for treatment group and center, adjusting for baseline HAM-D 17 total score. Missing values at week 8 were handled using the last observation carried forward (LOCF) approach.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.026
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Least Squares Mean Change
Estimated Value -1.6
Confidence Interval (2-Sided) 95%
-3.1 to -0.2
Estimation Comments [Not Specified]
3.Secondary Outcome
Title The CGI-I (Clinician's Global Impression of Improvement) Score at Week 8
Hide Description The CGI-I scale measures change from the baseline state at every visit after the baseline visit. It permits a global evaluation of the patient’s improvement over time. At the scheduled clinic visits, the clinician assessed the patient’s improvement relative to the symptoms at baseline on a CGI-I item using a 7-point scale, where 1 = very much improved and 7 = very much worse. The method of last observation carried forward was utilized for subjects who discontinued prematurely.
Time Frame Week 1, Week 2, Week 4, Week 6, Week 8
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT): the ITT population consisted of patients who were randomized, took at least 1 dose of study drug, and had at least 1 post-baseline efficacy endpoint measurement.
Arm/Group Title Vilazodone (ITT Population) Placebo (ITT Population)
Hide Arm/Group Description:
Vilazodone, 40 mg
placebo to match vilazodone
Overall Number of Participants Analyzed 231 231
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Units on a scale
2.5
(2.3 to 2.7)
2.8
(2.6 to 3.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vilazodone (ITT Population), Placebo (ITT Population)
Comments The model was an analysis of variance (ANOVA), with terms for treatment group and center. Missing values at week 8 were handled using the last observation carried forward (LOCF) approach.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Least Squares Mean Improve
Estimated Value -0.3
Confidence Interval (2-Sided) 95%
-0.5 to -0.1
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline to Week 8 in the HAM-A ( Hamilton Anxiety Rating Scale) Total Score
Hide Description The HAM-A is a rating scale developed to quantify the severity of anxiety. It consists of 14 items, each defined by a series of symptoms. Each item is rated on a 5-point scale, ranging from 0 (not present) to 4 (severe). Change from baseline in the HAM-A total score may range from -52 to 52 with negative value indicating improvement in anxiety symptom severity. The method of last observation carried forward was utilized for subjects who discontinued prematurely.
Time Frame Baseline, Week 1, Week 2, Week 4, Week 6, Week 8
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT): the ITT population consisted of patients who were randomized, took at least 1 dose of study drug, and had at least 1 post-baseline efficacy endpoint measurement.
Arm/Group Title Vilazodone (ITT Population) Placebo (ITT Population)
Hide Arm/Group Description:
Vilazodone, 40 mg
placebo to match vilazodone
Overall Number of Participants Analyzed 231 231
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Units on a scale
-7.0
(-8.0 to -5.9)
-5.7
(-6.8 to -4.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vilazodone (ITT Population), Placebo (ITT Population)
Comments The model was an analysis of covariance (ANCOVA), with terms for treatment group and center, adjusting for baseline HAM-A total score. Missing values at week 8 were handled using the last observation carried forward (LOCF) approach.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.037
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Least Squares Mean Change
Estimated Value -1.2
Confidence Interval (2-Sided) 95%
-2.4 to -0.1
Estimation Comments [Not Specified]
5.Secondary Outcome
Title MADRS (Montgomery-Asberg Depression Rating Scale) Response Rate at Week 8
Hide Description MADRS response was defined as ≥ 50% decrease from baseline in MADRS total score at Week 8. The response rate is the percentage of subjects in each treatment group meeting the criteria for response. The method of last observation carrier forward was utilized for subjects who discontinued prematurely.
Time Frame Baseline, Week 1, Week 2, Week 4, Week 6, Week 8
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT): the ITT population consisted of patients who were randomized, took at least 1 dose of study drug, and had at least 1 post-baseline efficacy endpoint measurement.
Arm/Group Title Vilazodone (ITT Population) Placebo (ITT Population)
Hide Arm/Group Description:
Vilazodone, 40 mg
placebo to match vilazodone
Overall Number of Participants Analyzed 231 231
Measure Type: Number
Unit of Measure: Participants
101 70
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vilazodone (ITT Population), Placebo (ITT Population)
Comments Cochran-Mantel-Haenszel tests were used to compare MADRS response rates between the treatment groups, stratifying by center. The asymptotic confidence interval of the risk difference was estimated by the normal approximation to the binomial distribution.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 0.134
Confidence Interval (2-Sided) 95%
0.047 to 0.221
Estimation Comments [Not Specified]
6.Secondary Outcome
Title MADRS (Montgomery-Asberg Depression Rating Scale) Remission Rate at Week 8
Hide Description MADRS remission was defined as a MADRS total score < 10 at Week 8. The remission rate is the percentage of subjects in each treatment group who met the criteria for remission. The method of last observation carried forward was utilized for subjects who discontinued prematurely.
Time Frame Baseline, Week 1, Week 2, Week 4, Week 6, Week 8
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT): the ITT population consisted of patients who were randomized, took at least 1 dose of study drug, and had at least 1 post-baseline efficacy endpoint measurement.
Arm/Group Title Vilazodone (ITT Population) Placebo (ITT Population)
Hide Arm/Group Description:
Vilazodone, 40 mg
placebo to match vilazodone
Overall Number of Participants Analyzed 231 231
Measure Type: Number
Unit of Measure: Participants
63 47
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vilazodone (ITT Population), Placebo (ITT Population)
Comments Cochran-Mantel-Haenszel tests were used to compare MADRS remission rates between the treatment groups, stratifying by center. The asymptotic confidence interval of the risk difference was estimated by the normal approximation to the binomial distribution.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.066
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 0.069
Confidence Interval (2-Sided) 95%
-0.008 to 0.147
Estimation Comments [Not Specified]
Time Frame 8 weeks
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Vilazodone (Safety Population) Placebo (Safety Population)
Hide Arm/Group Description Vilazodone, 40mg placebo to match vilazodone
All-Cause Mortality
Vilazodone (Safety Population) Placebo (Safety Population)
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Vilazodone (Safety Population) Placebo (Safety Population)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/235 (1.70%)      2/233 (0.86%)    
Cardiac disorders     
Angina pectoris  1 [1]  1/235 (0.43%)  1 0/233 (0.00%)  0
General disorders     
Chest pain  1  1/235 (0.43%)  1 0/233 (0.00%)  0
Hepatobiliary disorders     
Cholecystitis  1  1/235 (0.43%)  1 0/233 (0.00%)  0
Infections and infestations     
Pneumonia  1  1/235 (0.43%)  1 0/233 (0.00%)  0
Injury, poisoning and procedural complications     
Ankle fracture  1  0/235 (0.00%)  0 1/233 (0.43%)  1
Nervous system disorders     
Carotid arteriosclerosis  1 [2]  1/235 (0.43%)  1 0/233 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Asthma  1  0/235 (0.00%)  0 1/233 (0.43%)  2
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (11.1)
[1]
This subject also had the SAE of carotid arteriosclerosis.
[2]
This subject also had the SAE of angina pectoris
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Vilazodone (Safety Population) Placebo (Safety Population)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   148/235 (62.98%)      85/233 (36.48%)    
Gastrointestinal disorders     
Diarrhea  1  72/235 (30.64%)  91 25/233 (10.73%)  35
Dry Mouth  1  21/235 (8.94%)  21 9/233 (3.86%)  10
Nausea  1  61/235 (25.96%)  71 13/233 (5.58%)  15
Vomiting  1  12/235 (5.11%)  13 1/233 (0.43%)  2
Infections and infestations     
Upper Respiratory Infections  1  8/235 (3.40%)  8 21/233 (9.01%)  21
Nervous system disorders     
Dizziness  1  21/235 (8.94%)  21 9/233 (3.86%)  9
Headache  1  30/235 (12.77%)  32 24/233 (10.30%)  25
Psychiatric disorders     
Abnormal Dreams  1  14/235 (5.96%)  14 4/233 (1.72%)  4
Insomnia  1  17/235 (7.23%)  22 7/233 (3.00%)  7
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (11.1)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The investigators have the right to publish or permit the publication of any information or material relating to or arising out of this protocol after prior submission to PGxHealth provided that, if PGxHealth requests, the investigator will delay publication for a maximum of six months to enable PGxHealth to protect their rights in such information or material.
Results Point of Contact
Name/Title: Director of Medical Affairs
Organization: PGxHealth, LLC
Phone: 203-786-3400
Responsible Party: Carol R. Reed, MD, PGxHealth, LLC
ClinicalTrials.gov Identifier: NCT00683592     History of Changes
Other Study ID Numbers: CLDA-07-DP-02
First Submitted: May 21, 2008
First Posted: May 23, 2008
Results First Submitted: July 19, 2010
Results First Posted: October 27, 2010
Last Update Posted: October 27, 2010