VLZ-MD-01: Safety and Efficacy of Vilazodone in Major Depressive Disorder

• Sponsor: Forest Laboratories (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01473381
• Collaborator: (none)
• Enrollment: 1,162
• Locations: 54
• Arms: 4
• Duration (Months): 18
• Patients Per Site: 21.5
• Patients Per Site Per Month: 1.2

Study Details

Study Description

Brief Summary

The purpose of this study was to evaluate the efficacy, safety, and tolerability of 2 fixed dose levels of vilazodone compared to placebo in patients with major depressive disorder.

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder	Drug: Vilazodone; Drug: Placebo to citalopram; Drug: Placebo to vilazodone; Drug: Citalopram	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 1162 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Double-blind, Placebo- and Active-controlled, Fixed-dose Study of Vilazodone in Patients With Major Depressive Disorder
• Study Start Date: Dec 1, 2011
• Actual Primary Completion Date: Jun 1, 2013
• Actual Study Completion Date: Jun 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Participants received 2 placebo to vilazodone tablets, and 1 placebo to citalopram capsule orally once daily for the 11 weeks of the study.	Drug: Placebo to citalopram; Placebo to citalopram was supplied as a capsule.; Other Names: Celexa ; Drug: Placebo to vilazodone; Placebo to vilazodone was supplied as film-coated tablets.
Experimental: Vilazodone 20 mg/day Participants received 1 vilazodone tablet, 1 placebo to vilazodone tablet, and 1 placebo to citalopram capsule orally once daily for the 11 weeks of the study. Participants received vilazodone 10 mg/day during Week 1, vilazodone 20 mg/day during Weeks 2 to 10, and vilazodone 10 mg/day during Week 11.	Drug: Vilazodone; Vilazodone was supplied as film-coated tablets.; Other Names: Viibryd ; Drug: Placebo to citalopram; Placebo to citalopram was supplied as a capsule.; Other Names: Celexa ; Drug: Placebo to vilazodone; Placebo to vilazodone was supplied as film-coated tablets.
Experimental: Vilazodone 40 mg/day Participants received 1 placebo to vilazodone tablet, 1 vilazodone tablet, and 1 placebo to citalopram capsule orally once daily during Weeks 1 and 2 of the study. Participants received 2 vilazodone tablets and 1 placebo to citalopram capsule orally once daily during Weeks 3 -10 of the study. Participants received vilazodone 10 mg/day during Week 1, vilazodone 20/day mg during Week 2, and vilazodone 40 mg/day during Weeks 3 to 10. During Week 11, participants received vilazodone 20 mg/day for 4 days and 10 mg/day for 3 days.	Drug: Vilazodone; Vilazodone was supplied as film-coated tablets.; Other Names: Viibryd ; Drug: Placebo to citalopram; Placebo to citalopram was supplied as a capsule.; Other Names: Celexa ; Drug: Placebo to vilazodone; Placebo to vilazodone was supplied as film-coated tablets.
Active Comparator: Citalopram 40 mg/day Participants received 2 placebo vilazodone tablets, and 1 citalopram capsule once daily for the 11 weeks of the study. Participants received citalopram 20 mg/day during Weeks 1 and 2, citalopram 40 mg/day during Weeks 3 to 10, and citalopram 20 mg/day during Week 11.	Drug: Placebo to vilazodone; Placebo to vilazodone was supplied as film-coated tablets.; Drug: Citalopram; Citalopram was supplied as encapsulated tablets.; Other Names: Celexa

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at Week 10 [Baseline to Week 10]

   The MADRS is a clinician-rated scale based on participant interviews. The scale assesses depressive symptomatology that occurred in participants during the week preceding each interview. Participants were rated on 10 items: Apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. 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 of the 10 items and ranged from 0 to 60. A higher score indicates more depressive symptomatology. A negative change score indicates improvement.

Secondary Outcome Measures

1. Change From Baseline to Week 10 in the Clinical Global Impressions-Severity (CGI-S) Scale Score [Baseline to Week 10]

   The Clinical Global Impressions-Severity scale is a clinician-rated scale used to rate the severity of the participant's current state of mental illness compared with a patient population with major depressive disorder. In particular, the clinician is asked to respond to the following question: "Considering your total clinical experience with this population, how mentally ill is the patient at this time?" The patient is rated on the following 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. A higher score indicates more mental illness. A negative change score indicates improvement.

2. Percentage of Participants With a Montgomery-Åsberg Depression Rating Scale (MADRS) Sustained Response [Baseline to Week 10]

   The MADRS is a clinician-rated scale based on participant interviews. The scale assesses depressive symptomatology that occurred in participants during the week preceding each interview. Participants were rated on 10 items: Apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. 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 of the 10 items and ranged from 0 to 60. A higher score indicates more depressive symptomatology. A MADRS sustained response was defined as a MADRS total score ≤ 12 for at least the last 2 visits during the double-blind treatment period (Weeks 1-10). A total MADRS score ≤ 12 corresponds to an average score of 1 per item and is indicative of very low level of depressive symptoms.

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 036	Birmingham	Alabama	United States	35216
2	Forest Investigative Site 016	Dothan	Alabama	United States	36303
3	Forest Investigative Site 033	Scottsdale	Arizona	United States	85254
4	Forest Investigative Site 027	Fayetteville	Arkansas	United States	72703
5	Forest Investigative Site 029	Cerritos	California	United States	90703
6	Forest Investigative Site 002	Costa Mesa	California	United States	92626
7	Forest Investigative Site 019	Murrieta	California	United States	92562
8	Forest Investigative Site 025	Oceanside	California	United States	90703
9	Forest Investigative Site 043	Orange	California	United States	92868
10	Forest Investigative Site 003	Redlands	California	United States	92374
11	Forest Investigative Site 046	Sherman Oaks	California	United States	33026
12	Forest Investigative Site 057	Upland	California	United States	91786
13	Forest Investigative Site 034	Cromwell	Connecticut	United States	06416
14	Forest Investigative Site 038	Fort Myers	Florida	United States	33912
15	Forest Investigative Site 018	Gainsville	Florida	United States	32607
16	Forest Investigative Site 055	Hallandale Beach	Florida	United States	33003
17	Forest Investigative Site 063	Jacksonville	Florida	United States	32256
18	Forest Investigative Site 035	Miami	Florida	United States	33134
19	Forest Investigative Site 030	Orlando	Florida	United States	32806
20	Forest Investigative Site 062	Orlando	Florida	United States	32806
21	Forest Investigative Site 045	Pembroke Pines	Florida	United States	33026
22	Forest Investigative Site 051	Tampa	Florida	United States	33613
23	Forest Investigative Site 032	West Palm Beach	Florida	United States	33407
24	Forest Investigative Site 022	Winter Park	Florida	United States	32789
25	Forest Investigative Site 060	Atlanta	Georgia	United States	30328
26	Forest Investigative Site 037	Chicago	Illinois	United States	60634
27	Forest Investigative Site 050	Chicago	Illinois	United States	60640
28	Forest Investigative Site 040	Indianapolis	Indiana	United States	46260
29	Forest Investigative Site 012	Lafayette	Indiana	United States	47905
30	Forest Investigative Site 053	Prairie Village	Kansas	United States	66206
31	Forest Investigative Site 020	Baltimore	Maryland	United States	21208
32	Forest Investigative Site 031	Boston	Massachusetts	United States	02135
33	Forest Investigative Site 061	Las Vegas	Nevada	United States	89102
34	Forest Investigative Site 024	Willingboro	New Jersey	United States	08046
35	Forest Investigative Site 010	Albuquerque	New Mexico	United States	87109
36	Forest Investigative Site 011	Albuquerque	New Mexico	United States	87109
37	Forest Investigative Site 004	Brooklyn	New York	United States	11214
38	Forest Investigative Site 007	Cedarhurst	New York	United States	11516
39	Forest Investigative Site 058	New York City	New York	United States	10003
40	Forest Investigative Site 047	New York	New York	United States	10021
41	Forest Investigative Site 039	Cincinnati	Ohio	United States	45227
42	Forest Investigative Site 042	Oklahoma City	Oklahoma	United States	73112
43	Forest Investigative Site 048	Oklahoma City	Oklahoma	United States	73112
44	Forest Investigative Site 066	Portland	Oregon	United States	97210
45	Forest Investigative Site 014	Allentown	Pennsylvania	United States	18104
46	Forest Investigative Site 049	Bridgeville	Pennsylvania	United States	15017
47	Forest Investigative Site 064	Memphis	Tennessee	United States	38119
48	Forest Investigative Site 013	Austin	Texas	United States	78731
49	Forest Investigative Site 021	Dallas	Texas	United States	75230
50	Forest Investigative Site 059	Bellevue	Washington	United States	98007
51	Forest Investigative Site 065	Seattle	Washington	United States	98104
52	Forest Investigative Site 054	Spokane	Washington	United States	99204
53	Forest Investigative Site 052	Middleton	Wisconsin	United States	53562
54	Forest Investigative Site 056	Milwaukee	Wisconsin	United States	53223

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: NCT01473381
• Other Study ID Numbers: VLZ-MD-01
• First Posted: Nov 17, 2011
• Last Update Posted: Aug 8, 2014
• Last Verified: Aug 1, 2014

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

Study Results

Participant Flow

Arm/Group Title	Placebo	Vilazodone 20 mg/Day	Vilazodone 40 mg/Day	Citalopram 40 mg/Day
Arm/Group Description	Participants received 2 placebo to vilazodone tablets, and 1 placebo to citalopram capsule orally once daily for the 11 weeks of the study.	Participants received 1 vilazodone tablet, 1 placebo to vilazodone tablet, and 1 placebo to citalopram capsule orally once daily for the 11 weeks of the study. Participants received vilazodone 10 mg/day during Week 1, vilazodone 20 mg/day during Weeks 2 to 10, and vilazodone 10 mg/day during Week 11.	Participants received 1 placebo to vilazodone tablet, 1 vilazodone tablet, and 1 placebo to citalopram capsule orally once daily during Weeks 1 and 2 of the study. Participants received 2 vilazodone tablets and 1 placebo to citalopram capsule orally once daily during Weeks 3 -10 of the study. Participants received vilazodone 10 mg/day during Week 1, vilazodone 20/day mg during Week 2, and vilazodone 40 mg/day during Weeks 3 to 10. During Week 11, participants received vilazodone 20 mg/day for 4 days and 10 mg/day for 3 days.	Participants received 2 placebo vilazodone tablets, and 1 citalopram capsule once daily for the 11 weeks of the study. Participants received citalopram 20 mg/day during Weeks 1 and 2, citalopram 40 mg/day during Weeks 3 to 10, and citalopram 20 mg/day during Week 11.
Period Title: Overall Study
STARTED	290	292	291	289
Safety Population	281	288	287	282
COMPLETED	210	199	189	200
NOT COMPLETED	80	93	102	89

Baseline Characteristics

Arm/Group Title	Placebo	Vilazodone 20 mg/Day	Vilazodone 40 mg/Day	Citalopram 40 mg/Day	Total
Arm/Group Description	Participants received 2 placebo to vilazodone tablets, and 1 placebo to citalopram capsule orally once daily for the 11 weeks of the study.	Participants received 1 vilazodone tablet, 1 placebo to vilazodone tablet, and 1 placebo to citalopram capsule orally once daily for the 11 weeks of the study. Participants received vilazodone 10 mg/day during Week 1, vilazodone 20 mg/day during Weeks 2 to 10, and vilazodone 10 mg/day during Week 11.	Participants received 1 placebo to vilazodone tablet, 1 vilazodone tablet, and 1 placebo to citalopram capsule orally once daily during Weeks 1 and 2 of the study. Participants received 2 vilazodone tablets and 1 placebo to citalopram capsule orally once daily during Weeks 3 -10 of the study. Participants received vilazodone 10 mg/day during Week 1, vilazodone 20/day mg during Week 2, and vilazodone 40 mg/day during Weeks 3 to 10. During Week 11, participants received vilazodone 20 mg/day for 4 days and 10 mg/day for 3 days.	Participants received 2 placebo vilazodone tablets, and 1 citalopram capsule once daily for the 11 weeks of the study. Participants received citalopram 20 mg/day during Weeks 1 and 2, citalopram 40 mg/day during Weeks 3 to 10, and citalopram 20 mg/day during Week 11.	Total of all reporting groups
Overall Participants	281	288	287	282	1138
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	42.0 (13.0)	41.7 (12.7)	40.8 (13.2)	42.6 (12.6)	41.8 (12.8)
Age, Customized (participants) [Number]
< 20 years	5 1.8%	2 0.7%	9 3.1%	2 0.7%	18 1.6%
≥ 20-29 years	63 22.4%	62 21.5%	63 22%	53 18.8%	241 21.2%
≥ 30-39 years	48 17.1%	59 20.5%	68 23.7%	59 20.9%	234 20.6%
≥ 40-49 years	73 26%	88 30.6%	62 21.6%	76 27%	299 26.3%
≥ 50-59 years	66 23.5%	50 17.4%	62 21.6%	66 23.4%	244 21.4%
≥ 60 years	26 9.3%	27 9.4%	23 8%	26 9.2%	102 9%
Sex: Female, Male (Count of Participants)
Female	158 56.2%	166 57.6%	164 57.1%	165 58.5%	653 57.4%
Male	123 43.8%	122 42.4%	123 42.9%	117 41.5%	485 42.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	59 21%	55 19.1%	43 15%	53 18.8%	210 18.5%
Not Hispanic or Latino	222 79%	233 80.9%	244 85%	229 81.2%	928 81.5%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (participants) [Number]
White	197 70.1%	205 71.2%	202 70.4%	184 65.2%	788 69.2%
Black or African American	71 25.3%	73 25.3%	74 25.8%	83 29.4%	301 26.4%
Asian	7 2.5%	7 2.4%	3 1%	3 1.1%	20 1.8%
American Indian or Alaska Native	3 1.1%	0 0%	2 0.7%	4 1.4%	9 0.8%
Native Hawaiian or Other Pacific Islander	0 0%	1 0.3%	2 0.7%	1 0.4%	4 0.4%
Other	3 1.1%	2 0.7%	4 1.4%	7 2.5%	16 1.4%
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	82.27 (17.02)	82.55 (18.16)	82.45 (17.85)	82.37 (18.30)	82.41 (17.82)
Weight (kg) [Median (Full Range) ]
Median (Full Range) [kg]	82.50	82.40	82.10	79.50	81.60
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	169.03 (9.38)	168.86 (9.72)	169.87 (9.71)	169.78 (9.57)	169.39 (9.60)
Height (cm) [Median (Full Range) ]
Median (Full Range) [cm]	167.60	167.60	168.90	169.00	168.50
Body Mass Index (BMI) (kilograms per meter squared) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms per meter squared]	28.70 (5.40)	28.79 (5.49)	28.45 (5.43)	28.36 (5.17)	28.58 (5.37)
Body Mass Index (BMI) (kilograms per meter squared) [Median (Full Range) ]
Median (Full Range) [kilograms per meter squared]	28.30	28.20	27.80	27.90	28.10

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at Week 10
Description	The MADRS is a clinician-rated scale based on participant interviews. The scale assesses depressive symptomatology that occurred in participants during the week preceding each interview. Participants were rated on 10 items: Apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. 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 of the 10 items and ranged from 0 to 60. A higher score indicates more depressive symptomatology. A negative change score indicates improvement.
Time Frame	Baseline to Week 10

Outcome Measure Data

Analysis Population Description

Intent-to-treat population: All randomized participants who received at least 1 dose of placebo, vilazodone, or citalopram and who had a baseline and at least 1 post-baseline assessment of the MADRS total score.

Arm/Group Title	Placebo	Vilazodone 20 mg/Day	Vilazodone 40 mg/Day	Citalopram 40 mg/Day
Arm/Group Description	Participants received 2 placebo to vilazodone tablets, and 1 placebo to citalopram capsule orally once daily for the 11 weeks of the study.	Participants received 1 vilazodone tablet, 1 placebo to vilazodone tablet, and 1 placebo to citalopram capsule orally once daily for the 11 weeks of the study. Participants received vilazodone 10 mg/day during Week 1, vilazodone 20 mg/day during Weeks 2 to 10, and vilazodone 10 mg/day during Week 11.	Participants received 1 placebo to vilazodone tablet, 1 vilazodone tablet, and 1 placebo to citalopram capsule orally once daily during Weeks 1 and 2 of the study. Participants received 2 vilazodone tablets and 1 placebo to citalopram capsule orally once daily during Weeks 3 -10 of the study. Participants received vilazodone 10 mg/day during Week 1, vilazodone 20/day mg during Week 2, and vilazodone 40 mg/day during Weeks 3 to 10. During Week 11, participants received vilazodone 20 mg/day for 4 days and 10 mg/day for 3 days.	Participants received 2 placebo vilazodone tablets, and 1 citalopram capsule once daily for the 11 weeks of the study. Participants received citalopram 20 mg/day during Weeks 1 and 2, citalopram 40 mg/day during Weeks 3 to 10, and citalopram 20 mg/day during Week 11.
Measure Participants	281	288	284	280
Least Squares Mean (Standard Error) [Units on a scale]	-14.76 (0.62)	-17.33 (0.63)	-17.58 (0.65)	-17.50 (0.64)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Vilazodone 20 mg/Day
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0073
	Comments	P-value was adjusted for multiplicity.
	Method	Mixed-effect model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.57
	Confidence Interval	(2-Sided) 95%; -4.30 to -0.84
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Vilazodone 40 mg/Day
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0034
	Comments	P-value was adjusted for multiplicity.
	Method	Mixed-effect model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.82
	Confidence Interval	(2-Sided) 95%; -4.57 to -1.06
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Citalopram 40 mg/Day
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0020
	Comments	P-value was provided for assay sensitivity. It was not adjusted for multiplicity.
	Method	Mixed-effect model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.74
	Confidence Interval	(2-Sided) 95%; -4.48 to -1.00
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline to Week 10 in the Clinical Global Impressions-Severity (CGI-S) Scale Score
Description	The Clinical Global Impressions-Severity scale is a clinician-rated scale used to rate the severity of the participant's current state of mental illness compared with a patient population with major depressive disorder. In particular, the clinician is asked to respond to the following question: "Considering your total clinical experience with this population, how mentally ill is the patient at this time?" The patient is rated on the following 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. A higher score indicates more mental illness. A negative change score indicates improvement.
Time Frame	Baseline to Week 10

Outcome Measure Data

Analysis Population Description

Intent-to-treat population: All randomized participants who received at least 1 dose of placebo, vilazodone, or citalopram and who had a baseline and at least 1 post-baseline assessment of the MADRS total score.

Arm/Group Title	Placebo	Vilazodone 20 mg/Day	Vilazodone 40 mg/Day	Citalopram 40 mg/Day
Arm/Group Description	Participants received 2 placebo to vilazodone tablets, and 1 placebo to citalopram capsule orally once daily for the 11 weeks of the study.	Participants received 1 vilazodone tablet, 1 placebo to vilazodone tablet, and 1 placebo to citalopram capsule orally once daily for the 11 weeks of the study. Participants received vilazodone 10 mg/day during Week 1, vilazodone 20 mg/day during Weeks 2 to 10, and vilazodone 10 mg/day during Week 11.	Participants received 1 placebo to vilazodone tablet, 1 vilazodone tablet, and 1 placebo to citalopram capsule orally once daily during Weeks 1 and 2 of the study. Participants received 2 vilazodone tablets and 1 placebo to citalopram capsule orally once daily during Weeks 3 -10 of the study. Participants received vilazodone 10 mg/day during Week 1, vilazodone 20/day mg during Week 2, and vilazodone 40 mg/day during Weeks 3 to 10. During Week 11, participants received vilazodone 20 mg/day for 4 days and 10 mg/day for 3 days.	Participants received 2 placebo vilazodone tablets, and 1 citalopram capsule once daily for the 11 weeks of the study. Participants received citalopram 20 mg/day during Weeks 1 and 2, citalopram 40 mg/day during Weeks 3 to 10, and citalopram 20 mg/day during Week 11.
Measure Participants	281	288	284	280
Least Squares Mean (Standard Error) [Units on a scale]	-1.53 (0.08)	-1.88 (0.08)	-1.86 (0.08)	-1.88 (0.08)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Vilazodone 20 mg/Day
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0073
	Comments	P-value was adjusted for multiplicity.
	Method	Mixed-effect model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.35
	Confidence Interval	(2-Sided) 95%; -0.58 to -0.13
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Vilazodone 40 mg/Day
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0097
	Comments	P-value was adjusted for multiplicity.
	Method	Mixed-effect model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.33
	Confidence Interval	(2-Sided) 95%; -0.55 to -0.10
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Citalopram 40 mg/Day
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0025
	Comments	P-value was provided for assay sensitivity. It was not adjusted for multiplicity.
	Method	Mixed-effect model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.35
	Confidence Interval	(2-Sided) 95%; -0.57 to -0.12
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Percentage of Participants With a Montgomery-Åsberg Depression Rating Scale (MADRS) Sustained Response
Description	The MADRS is a clinician-rated scale based on participant interviews. The scale assesses depressive symptomatology that occurred in participants during the week preceding each interview. Participants were rated on 10 items: Apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. 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 of the 10 items and ranged from 0 to 60. A higher score indicates more depressive symptomatology. A MADRS sustained response was defined as a MADRS total score ≤ 12 for at least the last 2 visits during the double-blind treatment period (Weeks 1-10). A total MADRS score ≤ 12 corresponds to an average score of 1 per item and is indicative of very low level of depressive symptoms.
Time Frame	Baseline to Week 10

Outcome Measure Data

Analysis Population Description

Intent-to-treat population: All randomized participants who received at least 1 dose of placebo, vilazodone, or citalopram and who had a baseline and at least 1 post-baseline assessment of the MADRS total score.

Arm/Group Title	Placebo	Vilazodone 20 mg/Day	Vilazodone 40 mg/Day	Citalopram 40 mg/Day
Arm/Group Description	Participants received 2 placebo to vilazodone tablets, and 1 placebo to citalopram capsule orally once daily for the 11 weeks of the study.	Participants received 1 vilazodone tablet, 1 placebo to vilazodone tablet, and 1 placebo to citalopram capsule orally once daily for the 11 weeks of the study. Participants received vilazodone 10 mg/day during Week 1, vilazodone 20 mg/day during Weeks 2 to 10, and vilazodone 10 mg/day during Week 11.	Participants received 1 placebo to vilazodone tablet, 1 vilazodone tablet, and 1 placebo to citalopram capsule orally once daily during Weeks 1 and 2 of the study. Participants received 2 vilazodone tablets and 1 placebo to citalopram capsule orally once daily during Weeks 3 -10 of the study. Participants received vilazodone 10 mg/day during Week 1, vilazodone 20/day mg during Week 2, and vilazodone 40 mg/day during Weeks 3 to 10. During Week 11, participants received vilazodone 20 mg/day for 4 days and 10 mg/day for 3 days	Participants received 2 placebo vilazodone tablets, and 1 citalopram capsule once daily for the 11 weeks of the study. Participants received citalopram 20 mg/day during Weeks 1 and 2, citalopram 40 mg/day during Weeks 3 to 10, and citalopram 20 mg/day during Week 11.
Measure Participants	281	288	284	280
Number (95% Confidence Interval) [Percentage of participants]	26.3 9.4%	29.9 10.4%	33.5 11.7%	31.1 11%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Vilazodone 20 mg/Day
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3563
	Comments	P-value was adjusted for multiplicity.
	Method	Cochran-Mantel-Haenszel
	Comments	The Mean Difference (Final Values), as well as 95% Confidence Interval, are in units of percentage.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	3.5
	Confidence Interval	(2-Sided) 95%; -3.9 to 10.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Vilazodone 40 mg/Day
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1611
	Comments	P-value was adjusted for multiplicity.
	Method	Cochran-Mantel-Haenszel
	Comments	The Mean Difference (Final Values), as well as 95% Confidence Interval, are in units of percentage.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	7.1
	Confidence Interval	(2-Sided) 95%; -0.4 to 14.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Citalopram 40 mg/Day
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2672
	Comments	P-value was provided for assay sensitivity. It was not adjusted for multiplicity.
	Method	Cochran-Mantel-Haenszel
	Comments	The Mean Difference (Final Values), as well as 95% Confidence Interval, are in units of percentage.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	4.7
	Confidence Interval	(2-Sided) 95%; -2.7 to 12.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	From the time that the participant signs the informed consent form until 30 days after the last dose of treatment.
Adverse Event Reporting Description	Safety population: All randomized participants who received at least 1 dose of double-blind investigational product (placebo, vilazodone, or citalopram).
Arm/Group Title	Placebo		Vilazodone 20 mg/Day		Vilazodone 40 mg/Day		Citalopram 40 mg/Day
Arm/Group Description	Participants received 2 placebo to vilazodone tablets, and 1 placebo to citalopram capsule orally once daily for the 11 weeks of the study.		Participants received 1 vilazodone tablet, 1 placebo to vilazodone tablet, and 1 placebo to citalopram capsule orally once daily for the 11 weeks of the study. Participants received vilazodone 10 mg/day during Week 1, vilazodone 20 mg/day during Weeks 2 to 10, and vilazodone 10 mg/day during Week 11.		Participants received 1 placebo to vilazodone tablet, 1 vilazodone tablet, and 1 placebo to citalopram capsule orally once daily during Weeks 1 and 2 of the study. Participants received 2 vilazodone tablets and 1 placebo to citalopram capsule orally once daily during Weeks 3 -10 of the study. Participants received vilazodone 10 mg/day during Week 1, vilazodone 20/day mg during Week 2, and vilazodone 40 mg/day during Weeks 3 to 10. During Week 11, participants received vilazodone 20 mg/day for 4 days and 10 mg/day for 3 days.		Participants received 2 placebo vilazodone tablets, and 1 citalopram capsule once daily for the 11 weeks of the study. Participants received citalopram 20 mg/day during Weeks 1 and 2, citalopram 40 mg/day during Weeks 3 to 10, and citalopram 20 mg/day during Week 11.
All Cause Mortality
	Placebo		Vilazodone 20 mg/Day		Vilazodone 40 mg/Day		Citalopram 40 mg/Day
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Vilazodone 20 mg/Day		Vilazodone 40 mg/Day		Citalopram 40 mg/Day
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/281 (1.1%)		4/288 (1.4%)		4/287 (1.4%)		6/282 (2.1%)
Blood and lymphatic system disorders
Haemorrhagic anaemia	0/281 (0%)		0/288 (0%)		0/287 (0%)		1/282 (0.4%)
Cardiac disorders
Angina pectoris	1/281 (0.4%)		0/288 (0%)		0/287 (0%)		0/282 (0%)
Cardiomegaly	0/281 (0%)		1/288 (0.3%)		0/287 (0%)		0/282 (0%)
Gastrointestinal disorders
Diverticulitis	0/281 (0%)		0/288 (0%)		1/287 (0.3%)		1/282 (0.4%)
Gastric disorder	1/281 (0.4%)		0/288 (0%)		0/287 (0%)		0/282 (0%)
Immune system disorders
Asthma	0/281 (0%)		1/288 (0.3%)		0/287 (0%)		0/282 (0%)
Infections and infestations
Bronchitis	0/281 (0%)		1/288 (0.3%)		0/287 (0%)		0/282 (0%)
Pneumonia	1/281 (0.4%)		0/288 (0%)		0/287 (0%)		0/282 (0%)
Sepsis	0/281 (0%)		0/288 (0%)		1/287 (0.3%)		0/282 (0%)
Abscess Neck	1/281 (0.4%)		0/288 (0%)		0/287 (0%)		0/282 (0%)
Abscess Oral	1/281 (0.4%)		0/288 (0%)		0/287 (0%)		0/282 (0%)
Injury, poisoning and procedural complications
Accidental overdose	0/281 (0%)		1/288 (0.3%)		0/287 (0%)		0/282 (0%)
Ilium fracture	0/281 (0%)		0/288 (0%)		0/287 (0%)		1/282 (0.4%)
Intentional overdose	0/281 (0%)		0/288 (0%)		1/287 (0.3%)		0/282 (0%)
Road traffic accident	0/281 (0%)		0/288 (0%)		0/287 (0%)		1/282 (0.4%)
Traumatic renal injury	0/281 (0%)		0/288 (0%)		0/287 (0%)		1/282 (0.4%)
Investigations
Electrocardiogram ST segment abnormal	1/281 (0.4%)		0/288 (0%)		0/287 (0%)		0/282 (0%)
Musculoskeletal and connective tissue disorders
Back pain	1/281 (0.4%)		0/288 (0%)		0/287 (0%)		0/282 (0%)
Wrist fracture	0/281 (0%)		0/288 (0%)		0/287 (0%)		1/282 (0.4%)
Nervous system disorders
Dizziness	0/281 (0%)		1/288 (0.3%)		0/287 (0%)		0/282 (0%)
Migraine with aura	0/281 (0%)		0/288 (0%)		0/287 (0%)		1/282 (0.4%)
Pregnancy, puerperium and perinatal conditions
Abortion missed	0/281 (0%)		0/288 (0%)		0/287 (0%)		1/282 (0.4%)
Psychiatric disorders
Bipolar I disorder	0/281 (0%)		0/288 (0%)		1/287 (0.3%)		0/282 (0%)
Somnolence	0/281 (0%)		0/288 (0%)		1/287 (0.3%)		0/282 (0%)
Suicidal ideation	1/281 (0.4%)		0/288 (0%)		0/287 (0%)		1/282 (0.4%)
Suicide attempt	0/281 (0%)		0/288 (0%)		1/287 (0.3%)		0/282 (0%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	0/281 (0%)		1/288 (0.3%)		0/287 (0%)		0/282 (0%)
Status asthmaticus	0/281 (0%)		1/288 (0.3%)		0/287 (0%)		0/282 (0%)
Obstructive Airways Disorder	1/281 (0.4%)		0/288 (0%)		0/287 (0%)		0/282 (0%)
Surgical and medical procedures
Hospitalisation	0/281 (0%)		0/288 (0%)		0/287 (0%)		1/282 (0.4%)
Other (Not Including Serious) Adverse Events
	Placebo		Vilazodone 20 mg/Day		Vilazodone 40 mg/Day		Citalopram 40 mg/Day
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	124/281 (44.1%)		168/288 (58.3%)		177/287 (61.7%)		147/282 (52.1%)
Gastrointestinal disorders
Diarrhoea	26/281 (9.3%)		75/288 (26%)		76/287 (26.5%)		30/282 (10.6%)
Nausea	23/281 (8.2%)		62/288 (21.5%)		69/287 (24%)		55/282 (19.5%)
Dry mouth	14/281 (5%)		22/288 (7.6%)		19/287 (6.6%)		18/282 (6.4%)
Vomiting	7/281 (2.5%)		11/288 (3.8%)		19/287 (6.6%)		5/282 (1.8%)
General disorders
Fatigue	9/281 (3.2%)		11/288 (3.8%)		11/287 (3.8%)		20/282 (7.1%)
Nervous system disorders
Headache	39/281 (13.9%)		42/288 (14.6%)		41/287 (14.3%)		42/282 (14.9%)
Dizziness	20/281 (7.1%)		18/288 (6.3%)		18/287 (6.3%)		19/282 (6.7%)
Psychiatric disorders
Somnolence	10/281 (3.6%)		11/288 (3.8%)		18/287 (6.3%)		22/282 (7.8%)
Insomnia	8/281 (2.8%)		19/288 (6.6%)		16/287 (5.6%)		12/282 (4.3%)
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract infection	13/281 (4.6%)		14/288 (4.9%)		15/287 (5.2%)		14/282 (5%)
Nasopharyngitis	11/281 (3.9%)		12/288 (4.2%)		13/287 (4.5%)		15/282 (5.3%)

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.