Safety, Efficacy, and Tolerability of Vilazodone in Major Depressive Disorder

• Sponsor: Forest Laboratories (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01473394
• Collaborator: (none)
• Enrollment: 518
• Locations: 14
• Arms: 2
• Duration (Months): 14.1
• Patients Per Site: 37
• Patients Per Site Per Month: 2.6

Study Details

Study Description

Brief Summary

The purpose of this study was to further characterize the efficacy, safety, and tolerability of a single fixed dose level of vilazodone compared to placebo in patients with major depressive disorder.

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder	Drug: Dose-matched placebo; Drug: Vilazodone	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 518 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Double-blind, Placebo-controlled, Fixed-dose Study of Vilazodone in Patients With Major Depressive Disorder
• Study Start Date: Dec 1, 2011
• Actual Primary Completion Date: Feb 1, 2013
• Actual Study Completion Date: Feb 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Dose-matched placebo Participants received dose-matched placebo orally once daily for 9 weeks.	Drug: Dose-matched placebo; Dose-matched placebo was supplied as tablets.
Experimental: Vilazodone Participants received vilazodone orally once daily for 9 weeks, as follows: Week 1, 10 mg once a day; Week 2, 20 mg once a day; Weeks 3 to 8, 40 mg once a day; and Week 9 (down-taper period), 20 mg once a day for 4 days, then 10 mg once a day for 3 days.	Drug: Vilazodone; Vilazodone was supplied as tablets.; Other Names: Viibryd

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at Week 8 [Baseline to Week 8]

   The MADRS is a clinician-rated scale for assessing depressive symptomatology that had occurred in participants during the week preceding each interview. Patients were rated on 10 items to assess feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty concentrating, and lack of interest. Each item was scored on a 7-point scale from 0 (no symptoms) to 6 (symptoms of maximum severity). The total score was the sum of the scores on the 10 items and ranged from 0 to 60. A higher score indicated more depressive symptomatology. A negative change score indicated improvement.

Secondary Outcome Measures

1. Change From Baseline in Clinical Global Impressions-Severity (CGI-S) Score at Week 8 [Baseline to Week 8]

   The CGI-S is a clinician-rated scale for assessing the severity of the participant's current state of mental illness compared with a patient population with major depressive disorder. The clinician responded to the following question "Considering your total clinical experience with this population, how mentally ill is the participant at this time?" on a 7-point scale: 1=normal, not at all ill; 2=borderline ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among the most extremely ill patients. The scale ranges from 1 to 7. A higher score indicates more severe mental illness. A negative change score indicates improvement.

2. Percentage of Participants With a Montgomery-Åsberg Depression Rating Scale (MADRS) Sustained Response Rate [Baseline to Week 8]

   The MADRS Sustained response rate is defined as a MÅDRS total score ≤ 12 for at least the last 2 consecutive visits during the double-blind treatment period.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Men and women, 18-70 years of age.

• Currently meet the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision (DSM-IV-TR) criteria for Major Depressive Disorder.

• The patient's current major depressive episode must be at least 8 weeks and no longer than 12 months in duration.

Exclusion Criteria:

• Women who are pregnant, women who will be breastfeeding during the study, and women of childbearing potential who are not practicing a reliable method of birth control.

• Patients with a history of meeting DSM-IV-TR criteria for any:

• manic, hypomanic or mixed episode, including bipolar disorder and substance-induced manic, hypomanic, or mixed episode;

• any depressive episode with psychotic or catatonic features;

• panic disorder with or without agoraphobia;

• obsessive-compulsive disorder;

• schizophrenia, schizoaffective, or other psychotic disorder;

• bulimia or anorexia nervosa;

• presence of borderline personality disorder or antisocial personality disorder;

• mental retardation, dementia, amnesia, or other cognitive disorders;

• patients who are considered a suicide risk.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Forest Investigative Site 009	Beverly Hills	California	United States	90210
2	Forest Investigative Site 003	Encino	California	United States	91316
3	Forest Investigative Site 010	New port Beach	California	United States	92660
4	Forest Investigative Site 005	Jacksonville	Florida	United States	32216
5	Forest Investigative Site 004	Orlando	Florida	United States	32806
6	Forest Investigative Site 012	Atlanta	Georgia	United States	30328
7	Forest Investigative Site 001	Baltimore	Maryland	United States	21285
8	Forest Investigative Site 002	Dayton	Ohio	United States	45417
9	Forest Investigative Site 011	Philadelphia	Pennsylvania	United States	19104
10	Forest Investigative Site 015	Lincoln	Rhode Island	United States	02865
11	Forest Investigative Site 008	Memphis	Tennessee	United States	38119
12	Forest Investigative Site 016	San Antonio	Texas	United States	78229
13	Forest Investigative Site 006	Bellevue	Washington	United States	98007
14	Forest Investigative Site 013	Seattle	Washington	United States	98104

Sponsors and Collaborators

• Forest Laboratories

Investigators

• Study Director: Carl Gommoll, MS, Forest Laboratories

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Forest Laboratories
• ClinicalTrials.gov Identifier: NCT01473394
• Other Study ID Numbers: VLZ-MD-03
• First Posted: Nov 17, 2011
• Last Update Posted: Apr 3, 2014
• Last Verified: Feb 1, 2014

• Keywords provided by Forest Laboratories: Major depressive disorder; Depression
• Additional relevant MeSH terms: Disease; Depressive Disorder; Depression; Depressive Disorder, Major; Vilazodone Hydrochloride

Study Results

Participant Flow

Arm/Group Title	Dose-matched Placebo	Vilazodone
Arm/Group Description	Participants received dose-matched placebo orally once daily for 9 weeks.	Participants received vilazodone orally once daily for 9 weeks, as follows: Week 1, 10 mg once a day; Week 2, 20 mg once a day; Weeks 3 to 8, 40 mg once a day; and Week 9 (down-taper period), 20 mg once a day for 4 days, then 10 mg once a day for 3 days.
Period Title: Overall Study
STARTED	253	255
COMPLETED	208	212
NOT COMPLETED	45	43

Baseline Characteristics

Arm/Group Title	Dose-matched Placebo	Vilazodone	Total
Arm/Group Description	Participants received dose-matched placebo orally once daily for 9 weeks.	Participants received vilazodone orally once daily for 9 weeks, as follows: Week 1, 10 mg once a day; Week 2, 20 mg once a day; Weeks 3 to 8, 40 mg once a day; and Week 9 (down-taper period), 20 mg once a day for 4 days, then 10 mg once a day for 3 days.	Total of all reporting groups
Overall Participants	253	255	508
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	41.1 (13.2)	39.3 (12.8)	40.2 (13.0)
Age, Customized (Number) [Number]
< 20	7 2.8%	6 2.4%	13 2.6%
≥ 20-29	53 20.9%	68 26.7%	121 23.8%
≥ 30-39	54 21.3%	56 22%	110 21.7%
≥ 40-49	67 26.5%	62 24.3%	129 25.4%
≥ 50-59	48 19%	44 17.3%	92 18.1%
≥ 60	24 9.5%	19 7.5%	43 8.5%
Sex: Female, Male (Count of Participants)
Female	142 56.1%	131 51.4%	273 53.7%
Male	111 43.9%	124 48.6%	235 46.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	33 13%	42 16.5%	75 14.8%
Not Hispanic or Latino	220 87%	213 83.5%	433 85.2%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Number) [Number]
White	168 66.4%	174 68.2%	342 67.3%
Black or African American	70 27.7%	52 20.4%	122 24%
Asian	7 2.8%	14 5.5%	21 4.1%
American Indian or Alaska Native	0 0%	4 1.6%	4 0.8%
Native Hawaiian or Other Pacific Islander	1 0.4%	0 0%	1 0.2%
Other	7 2.8%	11 4.3%	18 3.5%
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	84.68 (17.84)	82.89 (18.39)	83.78 (18.12)
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	170.15 (9.12)	170.32 (9.60)	170.23 (9.36)
Body mass index (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	29.08 (5.50)	28.41 (5.47)	28.75 (5.49)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at Week 8
Description	The MADRS is a clinician-rated scale for assessing depressive symptomatology that had occurred in participants during the week preceding each interview. Patients were rated on 10 items to assess feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty concentrating, and lack of interest. Each item was scored on a 7-point scale from 0 (no symptoms) to 6 (symptoms of maximum severity). The total score was the sum of the scores on the 10 items and ranged from 0 to 60. A higher score indicated more depressive symptomatology. A negative change score indicated improvement.
Time Frame	Baseline to Week 8

Outcome Measure Data

Analysis Population Description

Intent-to-treat population: All randomized participants who received at least 1 dose of double-blind investigational product and who had a Baseline and at least 1 post-baseline assessment of the MADRS total score.

Arm/Group Title	Dose-matched Placebo	Vilazodone
Arm/Group Description	Participants received dose-matched placebo orally once daily for 9 weeks.	Participants received vilazodone orally once daily for 9 weeks, as follows: Week 1, 10 mg once a day; Week 2, 20 mg once a day; Weeks 3 to 8, 40 mg once a day; and Week 9 (down-taper period), 20 mg once a day for 4 days, then 10 mg once a day for 3 days.
Measure Participants	252	253
Least Squares Mean (Standard Error) [Units on a scale]	-11.0 (0.65)	-16.1 (0.64)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dose-matched Placebo, Vilazodone
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.00001
	Comments
	Method	Mixed-effects model for repeated measure
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-5.117
	Confidence Interval	(2-Sided) 95%; -6.886 to -3.347
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline in Clinical Global Impressions-Severity (CGI-S) Score at Week 8
Description	The CGI-S is a clinician-rated scale for assessing the severity of the participant's current state of mental illness compared with a patient population with major depressive disorder. The clinician responded to the following question "Considering your total clinical experience with this population, how mentally ill is the participant at this time?" on a 7-point scale: 1=normal, not at all ill; 2=borderline ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among the most extremely ill patients. The scale ranges from 1 to 7. A higher score indicates more severe mental illness. A negative change score indicates improvement.
Time Frame	Baseline to Week 8

Outcome Measure Data

Analysis Population Description

Intent-to-treat population: All randomized participants who received at least 1 dose of double-blind investigational product and who had a Baseline and at least 1 post-baseline assessment of the MADRS total score.

Arm/Group Title	Dose-matched Placebo	Vilazodone
Arm/Group Description	Participants received dose-matched placebo orally once daily for 9 weeks.	Participants received vilazodone orally once daily for 9 weeks, as follows: Week 1, 10 mg once a day; Week 2, 20 mg once a day; Weeks 3 to 8, 40 mg once a day; and Week 9 (down-taper period), 20 mg once a day for 4 days, then 10 mg once a day for 3 days.
Measure Participants	252	253
Least Squares Mean (Standard Error) [Units on a scale]	-1.2 (0.08)	-1.8 (0.08)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dose-matched Placebo, Vilazodone
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.00001
	Comments
	Method	Mixed-effects model for repeated measure
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-0.622
	Confidence Interval	(2-Sided) 95%; -0.845 to -0.399
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Percentage of Participants With a Montgomery-Åsberg Depression Rating Scale (MADRS) Sustained Response Rate
Description	The MADRS Sustained response rate is defined as a MÅDRS total score ≤ 12 for at least the last 2 consecutive visits during the double-blind treatment period.
Time Frame	Baseline to Week 8

Outcome Measure Data

Analysis Population Description

Intent-to-treat population: All randomized participants who received at least 1 dose of double-blind investigational product and who had a Baseline and at least 1 post-baseline assessment of the MADRS total score.

Arm/Group Title	Dose-matched Placebo	Vilazodone
Arm/Group Description	Participants received dose-matched placebo orally once daily for 9 weeks.	Participants received vilazodone orally once daily for 9 weeks, as follows: Week 1, 10 mg once a day; Week 2, 20 mg once a day; Weeks 3 to 8, 40 mg once a day; and Week 9 (down-taper period), 20 mg once a day for 4 days, then 10 mg once a day for 3 days.
Measure Participants	252	253
Number (95% Confidence Interval) [Percentage of participants]	17.1 6.8%	27.3 10.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dose-matched Placebo, Vilazodone
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0047
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	10.2
	Confidence Interval	(2-Sided) 95%; 3.0 to 17.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	The Mean Difference (Final Values), as well as the 95% Confidence Interval, are in units of percentage.

Adverse Events

Time Frame	Adverse events were reported from the time the participant signs the informed consent form until 30 days after the last dose of treatment (up to 13 weeks).
Adverse Event Reporting Description	Safety population: All randomized participants who received at least 1 dose of double-blind investigational product. The Severe Adverse Event data presented here is for the safety population. The Other Adverse Event data presented here is for the safety population during the 8 week double-blind treatment period.
Arm/Group Title	Dose-matched Placebo		Vilazodone
Arm/Group Description	Participants received dose-matched placebo orally once daily for 9 weeks.		Participants received vilazodone orally once daily for 9 weeks, as follows: Week 1, 10 mg once a day; Week 2, 20 mg once a day; Weeks 3 to 8, 40 mg once a day; and Week 9 (down-taper period), 20 mg once a day for 4 days, then 10 mg once a day for 3 days.
All Cause Mortality
	Dose-matched Placebo		Vilazodone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Dose-matched Placebo		Vilazodone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/253 (0.8%)		3/255 (1.2%)
Cardiac disorders
Myocardial infarction	0/253 (0%)		1/255 (0.4%)
General disorders
Non-cardiac chest pain	0/253 (0%)		1/255 (0.4%)
Injury, poisoning and procedural complications
Intentional overdose	1/253 (0.4%)		0/255 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer	1/253 (0.4%)		0/255 (0%)
Psychiatric disorders
Suicidal ideation	0/253 (0%)		1/255 (0.4%)
Suicide attempt	1/253 (0.4%)		0/255 (0%)
Other (Not Including Serious) Adverse Events
	Dose-matched Placebo		Vilazodone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	78/253 (30.8%)		149/255 (58.4%)
Gastrointestinal disorders
Diarrhoea	26/253 (10.3%)		83/255 (32.5%)
Nausea	21/253 (8.3%)		63/255 (24.7%)
Infections and infestations
Upper respiratory tract infection	14/253 (5.5%)		10/255 (3.9%)
Nervous system disorders
Headache	26/253 (10.3%)		24/255 (9.4%)
Dizziness	7/253 (2.8%)		18/255 (7.1%)
Psychiatric disorders
Insomnia	3/253 (1.2%)		15/255 (5.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

All data generated in this study will be the property of Forest Research Institute, Inc. An integrated clinical and statistical report will be prepared at the completion of the study. Publication of the results by the Investigator will be subject to mutual agreement between the Investigator and Forest Research Institute, Inc.