Trial Outcomes & Findings for Randomized, Double-Blind, Placebo Controlled Study of Vilazodone's Efficacy, Safety, and Biomarkers of Response in Major Depressive Disorder (MDD) (NCT NCT00683592)

NCT ID: NCT00683592

Last Updated: 2010-10-27

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 481 participants
• Primary outcome timeframe: Baseline, Week 1, Week 2, Week 4, Week 6, Week 8
• Results posted on: 2010-10-27

Participant Flow

Recruitment period was 31Mar2008 to 10Feb2009.

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.

Participant milestones

Measure	Vilazodone Vilazodone titrated to 40mg. Two tablets per day.	Placebo Placebo to match vilazodone. Two tablets per day.
Overall Study STARTED	240	241
Overall Study Intent to Treat Population	231	232
Overall Study Safety Population	235	233
Overall Study COMPLETED	193	195
Overall Study NOT COMPLETED	47	46

Reasons for withdrawal

Measure	Vilazodone Vilazodone titrated to 40mg. Two tablets per day.	Placebo Placebo to match vilazodone. Two tablets per day.
Overall Study Adverse Event	12	4
Overall Study Withdrawal by Subject	11	11
Overall Study Lost to Follow-up	17	17
Overall Study Lack of Efficacy	3	7
Overall Study Physician Decision	0	1
Overall Study Non-compliance	3	5
Overall Study Other	1	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Vilazodone (ITT Population) n=231 Participants Vilazodone, 40 mg	Placebo (ITT Population) n=232 Participants placebo to match vilazodone	Total n=463 Participants Total of all reporting groups
Age Continuous	41.1 years STANDARD_DEVIATION 12.22 • n=5 Participants	42.4 years STANDARD_DEVIATION 12.49 • n=7 Participants	41.7 years STANDARD_DEVIATION 12.36 • n=5 Participants
Sex: Female, Male Female	138 Participants n=5 Participants	123 Participants n=7 Participants	261 Participants n=5 Participants
Sex: Female, Male Male	93 Participants n=5 Participants	109 Participants n=7 Participants	202 Participants n=5 Participants
Region of Enrollment United States	231 participants n=5 Participants	232 participants n=7 Participants	463 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 1, Week 2, Week 4, Week 6, Week 8

Population: 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.

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.

Outcome measures

Measure	Vilazodone (ITT Population) n=231 Participants Vilazodone, 40 mg	Placebo (ITT Population) n=231 Participants placebo to match vilazodone
Change From Baseline to Week 8 in the MADRS (Montgomery-Asberg Depression Rating Scale) Total Score.	-13.3 Units on a scale Interval -15.1 to -11.5	-10.8 Units on a scale Interval -12.6 to -9.1

SECONDARY outcome

Timeframe: Baseline, week 1, week 2, week 4, week 6, week 8

Population: 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.

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.

Outcome measures

Measure	Vilazodone (ITT Population) n=231 Participants Vilazodone, 40 mg	Placebo (ITT Population) n=231 Participants placebo to match vilazodone
Change From Baseline to Week 8 in the HAM-D 17 (17-Item Hamilton Rating Scale for Depression) Total Score	-10.7 Units on a scale Interval -12.1 to -9.4	-9.1 Units on a scale Interval -10.4 to -7.7

SECONDARY outcome

Timeframe: Week 1, Week 2, Week 4, Week 6, Week 8

Population: 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.

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.

Outcome measures

Measure	Vilazodone (ITT Population) n=231 Participants Vilazodone, 40 mg	Placebo (ITT Population) n=231 Participants placebo to match vilazodone
The CGI-I (Clinician's Global Impression of Improvement) Score at Week 8	2.5 Units on a scale Interval 2.3 to 2.7	2.8 Units on a scale Interval 2.6 to 3.0

SECONDARY outcome

Timeframe: Baseline, Week 1, Week 2, Week 4, Week 6, Week 8

Population: 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.

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.

Outcome measures

Measure	Vilazodone (ITT Population) n=231 Participants Vilazodone, 40 mg	Placebo (ITT Population) n=231 Participants placebo to match vilazodone
Change From Baseline to Week 8 in the HAM-A ( Hamilton Anxiety Rating Scale) Total Score	-7.0 Units on a scale Interval -8.0 to -5.9	-5.7 Units on a scale Interval -6.8 to -4.7

SECONDARY outcome

Timeframe: Baseline, Week 1, Week 2, Week 4, Week 6, Week 8

Population: 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.

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.

Outcome measures

Measure	Vilazodone (ITT Population) n=231 Participants Vilazodone, 40 mg	Placebo (ITT Population) n=231 Participants placebo to match vilazodone
MADRS (Montgomery-Asberg Depression Rating Scale) Response Rate at Week 8	101 Participants	70 Participants

SECONDARY outcome

Timeframe: Baseline, Week 1, Week 2, Week 4, Week 6, Week 8

Population: 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.

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.

Outcome measures

Measure	Vilazodone (ITT Population) n=231 Participants Vilazodone, 40 mg	Placebo (ITT Population) n=231 Participants placebo to match vilazodone
MADRS (Montgomery-Asberg Depression Rating Scale) Remission Rate at Week 8	63 Participants	47 Participants

Adverse Events

Vilazodone (Safety Population)

Serious events: 4 serious events

Other events: 148 other events

Deaths: 0 deaths

Placebo (Safety Population)

Serious events: 2 serious events

Other events: 85 other events

Deaths: 0 deaths

Serious adverse events

Measure	Vilazodone (Safety Population) n=235 participants at risk Vilazodone, 40mg	Placebo (Safety Population) n=233 participants at risk placebo to match vilazodone
Cardiac disorders Angina pectoris	0.43% 1/235 • Number of events 1 • 8 weeks	0.00% 0/233 • 8 weeks
Injury, poisoning and procedural complications Ankle fracture	0.00% 0/235 • 8 weeks	0.43% 1/233 • Number of events 1 • 8 weeks
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/235 • 8 weeks	0.43% 1/233 • Number of events 2 • 8 weeks
Nervous system disorders Carotid arteriosclerosis	0.43% 1/235 • Number of events 1 • 8 weeks	0.00% 0/233 • 8 weeks
General disorders Chest pain	0.43% 1/235 • Number of events 1 • 8 weeks	0.00% 0/233 • 8 weeks
Hepatobiliary disorders Cholecystitis	0.43% 1/235 • Number of events 1 • 8 weeks	0.00% 0/233 • 8 weeks
Infections and infestations Pneumonia	0.43% 1/235 • Number of events 1 • 8 weeks	0.00% 0/233 • 8 weeks

Other adverse events

Measure	Vilazodone (Safety Population) n=235 participants at risk Vilazodone, 40mg	Placebo (Safety Population) n=233 participants at risk placebo to match vilazodone
Psychiatric disorders Abnormal Dreams	6.0% 14/235 • Number of events 14 • 8 weeks	1.7% 4/233 • Number of events 4 • 8 weeks
Gastrointestinal disorders Diarrhea	30.6% 72/235 • Number of events 91 • 8 weeks	10.7% 25/233 • Number of events 35 • 8 weeks
Nervous system disorders Dizziness	8.9% 21/235 • Number of events 21 • 8 weeks	3.9% 9/233 • Number of events 9 • 8 weeks
Gastrointestinal disorders Dry Mouth	8.9% 21/235 • Number of events 21 • 8 weeks	3.9% 9/233 • Number of events 10 • 8 weeks
Nervous system disorders Headache	12.8% 30/235 • Number of events 32 • 8 weeks	10.3% 24/233 • Number of events 25 • 8 weeks
Psychiatric disorders Insomnia	7.2% 17/235 • Number of events 22 • 8 weeks	3.0% 7/233 • Number of events 7 • 8 weeks
Gastrointestinal disorders Nausea	26.0% 61/235 • Number of events 71 • 8 weeks	5.6% 13/233 • Number of events 15 • 8 weeks
Infections and infestations Upper Respiratory Infections	3.4% 8/235 • Number of events 8 • 8 weeks	9.0% 21/233 • Number of events 21 • 8 weeks
Gastrointestinal disorders Vomiting	5.1% 12/235 • Number of events 13 • 8 weeks	0.43% 1/233 • Number of events 2 • 8 weeks

Additional Information

Director of Medical Affairs

PGxHealth, LLC

Phone: 203-786-3400

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER