Safety and Efficacy of Vilazodone in Pediatric Patients With Major Depressive Disorder (VLZ-MD-22)

• Sponsor: Forest Laboratories (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02372799
• Collaborator: (none)
• Enrollment: 473
• Locations: 60
• Arms: 3
• Actual Duration (Months): 42.4
• Patients Per Site: 7.9
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy, safety, and tolerability of vilazodone compared with placebo in pediatric outpatients (7-17 years of age) with major depressive disorder.

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder	Drug: Vilazodone; Drug: Placebo; Drug: Fluoxetine	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 473 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Double-blind, Placebo- and Active-Controlled Parallel-Group Evaluation of the Safety and Efficacy of Vilazodone in Pediatric Patients With Major Depressive Disorder
• Actual Study Start Date: Feb 28, 2015
• Actual Primary Completion Date: Sep 11, 2018
• Actual Study Completion Date: Sep 11, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Vilazodone Vilazodone tablets, 5mg, 10mg and 20mg. Oral administration, once per day.	Drug: Vilazodone; Other Names: Viibryd
Placebo Comparator: Placebo Dose-matched placebo tablets or capsules, oral administration, once per day.	Drug: Placebo
Active Comparator: Fluoxetine Fluoxetine capsules, 10mg and 20 mg. Oral administration, once per day.	Drug: Fluoxetine; Other Names: Prozac

Outcome Measures

Primary Outcome Measures

1. Change in Children's Depression Rating Scale-Revised (CDRS-R) Total Score [From Baseline to Week 8]

   The Children's Depression Rating Scale-Revised (CDRS-R) total score ranges from 17 (minimal or no symptoms of depression) to 133 (indicative of depression) is a semi-structured, clinician-rated instrument designed for use with children and adolescents between the ages of 6 to 17 years of age and their caregivers. The CDRS-R evaluates the presence and severity of symptoms commonly associated with depression in childhood.

Secondary Outcome Measures

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

   The Clinical Global Impressions-Severity (CGI-S) is a clinician-rated instrument used to rate the severity of the patient's current state of mental illness compared with the clinician's total experience with patients with major depressive disorder (MDD). The severity of the patient's MDD was rated on a scale from 1 to 7, with 1 indicating a normal state and 7 indicating a patient who is among the most extremely ill patients.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 7 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or Female outpatients between 7-17 years of age

• Primary diagnosis of Major Depressive Disorder (MDD)

• Children's Depression Rating Scale-Revised (CDRS-R) score of 40 or greater

• Clinical Global Impressions-Severity (CGI-S) score of 4 or greater

Exclusion Criteria:

• Current (past 3 months) principal Diagnostic and Statistical Manual of Mental Disorders, 4th edition, Text Revision (DSM-IV-TR) based diagnosis of an axis disorder other than major depressive disorder (MDD) that is the primary focus of treatment.

• History of suicidal behavior, or requires precaution against suicide

• Not generally healthy medical condition

• Seizure disorder

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Alliance Clinical Research	Birmingham	Alabama	United States	35213
2	Harmonex Neuroscience Research	Dothan	Alabama	United States	36303
3	Phoenix Children's Hospital	Phoenix	Arizona	United States	85016
4	Woodland International Research Group, INC	Little Rock	Arkansas	United States	72211
5	CITrials - Bellflower	Bellflower	California	United States	90706
6	ATP Clinical Research	Costa Mesa	California	United States	92626
7	Behavioral Research Specialists, LLC	Glendale	California	United States	91206
8	PCSD - Feighner Research	San Diego	California	United States	92108
9	Pacific Clinical Research Medical Group	Upland	California	United States	91786
10	Hartford Hospital	Hartford	Connecticut	United States	06106
11	Children's National Medical Center	Washington	District of Columbia	United States	20010
12	Palm Springs Research, LLC	Hialeah	Florida	United States	33012
13	IMIC Inc.	Homestead	Florida	United States	33030
14	Clinical Neuroscience Solutions, Inc.	Jacksonville	Florida	United States	32256
15	Osceola Mental Health dba Park Place Behavioral Health Care	Kissimmee	Florida	United States	34741
16	Innovative Clinical Research, Inc.	Lauderhill	Florida	United States	33319
17	Clinical Neuroscience Solutions, Inc.	Orlando	Florida	United States	32801
18	Institute for Advanced Medical Research	Alpharetta	Georgia	United States	30005
19	Atlantic Center for Medical Research	Atlanta	Georgia	United States	30331
20	Northwest Behavioral Research Center	Marietta	Georgia	United States	30060
21	Capstone Clinical Research	Libertyville	Illinois	United States	60048
22	Baber Research Group	Naperville	Illinois	United States	60563
23	Neuroscience Research Institute Inc.	Oak Park	Illinois	United States	60301
24	Goldpoint Clinical Research, LLC	Indianapolis	Indiana	United States	46260
25	Psychiatric Associates	Overland Park	Kansas	United States	66211
26	Lake Charles Clinical Trials	Lake Charles	Louisiana	United States	70629
27	Hugo W Moser Research Institute at Kennedy Krieger, Inc.	Baltimore	Maryland	United States	21205
28	Pharmsite Research Inc.	Baltimore	Maryland	United States	21208
29	NeuroScientific Insights	Rockville	Maryland	United States	20852
30	Baystate Medical Center	Springfield	Massachusetts	United States	01199
31	Adams Clinical Trials, LLC	Watertown	Massachusetts	United States	02472
32	Millennium Psychiatric Associates	Creve Coeur	Missouri	United States	63141
33	St. Charles Psychiatric Associates - Midwest Research Group	Saint Charles	Missouri	United States	63304
34	BioScience Research LLC	Mount Kisco	New York	United States	10549
35	Manhattan Behavioral Medicine	New York	New York	United States	10022
36	Finger Lakes Clinical research	Rochester	New York	United States	14618
37	Richmond Behavioral Associates	Staten Island	New York	United States	10312
38	Haidar Almhana Nieding LLC	Avon Lake	Ohio	United States	44012
39	Neuro-Behavioral Clinical Research, Inc	Canton	Ohio	United States	44718
40	University of Cincinnati	Cincinnati	Ohio	United States	45219
41	University Hospitals Cleveland Medical Center, Psychiatry	Cleveland	Ohio	United States	44106
42	Ohio State Univ. Dept of Psychiatry	Columbus	Ohio	United States	43210
43	Professional Psychiatric Services	Mason	Ohio	United States	45040
44	IPS Research Company	Oklahoma City	Oklahoma	United States	73103
45	Cutting Edge Research Group	Oklahoma City	Oklahoma	United States	73116
46	Research Strategies of Memphis LLC	Memphis	Tennessee	United States	38119
47	FutureSearch Clinical trials, Inc.	Austin	Texas	United States	78731
48	BioBehavioral Research of Austin, PC	Austin	Texas	United States	78759
49	University of TX Southwestern Medical Ctr	Dallas	Texas	United States	75235
50	Bayou City Research Ltd	Houston	Texas	United States	77007
51	Houston Endoscopy and Research Ctr	Houston	Texas	United States	77079
52	Research Across America	Plano	Texas	United States	75234
53	Focus and Balance	San Antonio	Texas	United States	78229
54	Family Psychiatry of The Woodlands	The Woodlands	Texas	United States	77381
55	Ericksen Research and Development	Clinton	Utah	United States	84015
56	UVA Center for Psychopharmacology Research in Youth	Charlottesville	Virginia	United States	22903
57	Northwest Clinical Research Center	Bellevue	Washington	United States	98007
58	Core Clinical Research	Everett	Washington	United States	98033
59	Okanagan Clinical Trials	Kelowna	British Columbia	Canada	V1Y 1Z9
60	Paediatric Sleep Research Inc	Toronto	Ontario	Canada	M5B 1T8

Sponsors and Collaborators

• Forest Laboratories

Investigators

• Study Director: Emily McCusker, PhD, Forest Research Institute, an affiliate of Allergan plc.

Study Documents (Full-Text)

• Study Protocol - Apr 15, 2015
• Statistical Analysis Plan - Oct 5, 2018

More Information

Publications

None provided.

• Responsible Party: Forest Laboratories
• ClinicalTrials.gov Identifier: NCT02372799
• Other Study ID Numbers: VLZ-MD-22
• First Posted: Feb 26, 2015
• Last Update Posted: Oct 1, 2019
• Last Verified: Sep 1, 2019

• Additional relevant MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major; Fluoxetine; Vilazodone Hydrochloride

Study Results

Participant Flow

Pre-assignment Detail	Randomization and treatment assignment were based on a randomization scheme prepared by Allergan Biostatistics prior to the start of the study

Arm/Group Title	Placebo	Vilazodone	Fluoxetine
Arm/Group Description	Dose-matched placebo tablets or capsules, oral administration, once per day.	Vilazodone tablets 15-30 mg. Oral administration, once per day.	Fluoxetine capsules 20 mg. Oral administration, once per day.
Period Title: Treatment Period
STARTED	186	187	97
COMPLETED	152	155	82
NOT COMPLETED	34	32	15
Period Title: Treatment Period
STARTED	152	159	82
COMPLETED	151	157	80
NOT COMPLETED	1	2	2

Baseline Characteristics

Arm/Group Title	Placebo	Vilazodone	Fluoxetine	Total
Arm/Group Description	Dose-matched placebo tablets or capsules, oral administration, once per day.	Vilazodone tablets 15-30 mg. Oral administration, once per day.	Fluoxetine capsules 20 mg. Oral administration, once per day.	Total of all reporting groups
Overall Participants	186	187	97	470
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	13 (2.9)	13 (2.9)	13.2 (2.8)	13 (2.9)
Age, Customized (Count of Participants)
7-11	61 32.8%	55 29.4%	30 30.9%	146 31.1%
12-17	125 67.2%	132 70.6%	67 69.1%	324 68.9%
Sex: Female, Male (Count of Participants)
Female	106 57%	126 67.4%	51 52.6%	283 60.2%
Male	80 43%	61 32.6%	46 47.4%	187 39.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	27 14.5%	25 13.4%	12 12.4%	64 13.6%
Not Hispanic or Latino	159 85.5%	162 86.6%	85 87.6%	406 86.4%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
White	118 63.4%	121 64.7%	60 61.9%	299 63.6%
Black or African American	57 30.6%	58 31%	30 30.9%	145 30.9%
Asian	5 2.7%	1 0.5%	1 1%	7 1.5%
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	1 0.5%	2 1.1%	0 0%	3 0.6%
Other	5 2.7%	5 2.7%	5 5.2%	15 3.2%
Missing	0 0%	0 0%	1 1%	1 0.2%
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	59.13 (24.29)	61.35 (24.79)	59.38 (21.14)	60.07 (23.86)
Body Mass Index (BMI) (kg/m2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m2]	23.31 (6.85)	24.25 (7.58)	23.48 (6.66)	23.72 (7.11)
CDRS-R total score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	57.3 (9.2)	58.3 (9.2)	58 (8.8)	57.8 (9.1)
CGI-S score (Units on a Scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Units on a Scale]	4.6 (0.6)	4.7 (0.6)	4.6 (0.6)	4.6 (0.6)

Outcome Measures

1. Primary Outcome

Title	Change in Children's Depression Rating Scale-Revised (CDRS-R) Total Score
Description	The Children's Depression Rating Scale-Revised (CDRS-R) total score ranges from 17 (minimal or no symptoms of depression) to 133 (indicative of depression) is a semi-structured, clinician-rated instrument designed for use with children and adolescents between the ages of 6 to 17 years of age and their caregivers. The CDRS-R evaluates the presence and severity of symptoms commonly associated with depression in childhood.
Time Frame	From Baseline to Week 8

Outcome Measure Data

Analysis Population Description

The Intent-to-Treat (ITT) Population will consist of all patients in the Safety Population who had baseline and at least 1 postbaseline assessment of the Children's Depression Rating Scale-Revised (CDRS-R) total score.

Arm/Group Title	Placebo	Vilazodone	Fluoxetine
Arm/Group Description	Dose-matched placebo tablets or capsules, oral administration, once per day.	Vilazodone tablets 15-30 mg. Oral administration, once per day.	Fluoxetine capsules 20 mg. Oral administration, once per day.
Measure Participants	182	186	97
Least Squares Mean (Standard Error) [units on a scale]	-20.32 (0.983)	-20.72 (0.977)	-22.71 (1.320)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Vilazodone
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7662
	Comments
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	LSMD
	Estimated Value	-0.40
	Confidence Interval	(2-Sided) 95%; -3.08 to 2.27
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Fluoxetine
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1433
	Comments
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	LSMD
	Estimated Value	-2.39
	Confidence Interval	(2-Sided) 95%; -5.60 to 0.81
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change in Clinical Global Impressions-Severity (CGI-S) Score
Description	The Clinical Global Impressions-Severity (CGI-S) is a clinician-rated instrument used to rate the severity of the patient's current state of mental illness compared with the clinician's total experience with patients with major depressive disorder (MDD). The severity of the patient's MDD was rated on a scale from 1 to 7, with 1 indicating a normal state and 7 indicating a patient who is among the most extremely ill patients.
Time Frame	From Baseline to Week 8

Outcome Measure Data

Analysis Population Description

The Intent-to-Treat (ITT) Population will consist of all patients in the Safety Population who had baseline and at least 1 postbaseline assessment of the Children's Depression Rating Scale-Revised (CDRS-R) total score.

Arm/Group Title	Placebo	Vilazodone	Fluoxetine
Arm/Group Description	Dose-matched placebo tablets or capsules, oral administration, once per day.	Vilazodone tablets 15-30 mg. Oral administration, once per day.	Fluoxetine capsules 20 mg. Oral administration, once per day.
Measure Participants	182	186	97
Least Squares Mean (Standard Error) [units on a scale]	-1.52 (0.097)	-1.57 (0.096)	-1.72 (0.130)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Vilazodone
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7387
	Comments
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	LSMD
	Estimated Value	-0.04
	Confidence Interval	(2-Sided) 95%; -0.31 to 0.22
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Fluoxetine
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2158
	Comments
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	LSMD
	Estimated Value	-0.20
	Confidence Interval	(2-Sided) 95%; -0.52 to 0.12
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Adverse event data was collected from the participant's signing of the Informed Consent Forum until 30 days after the last does of study treatment, spanning a period of 10 to 13 weeks.
Arm/Group Title	Placebo		Vilazodone		Fluoxetine
Arm/Group Description	Dose-matched placebo tablets or capsules, oral administration, once per day.		Vilazodone tablets 15-30 mg. Oral administration, once per day.		Fluoxetine capsules 20 mg. Oral administration, once per day.
All Cause Mortality
	Placebo		Vilazodone		Fluoxetine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/186 (0%)		0/187 (0%)		0/97 (0%)
Serious Adverse Events
	Placebo		Vilazodone		Fluoxetine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/186 (0.5%)		0/187 (0%)		6/97 (6.2%)
Infections and infestations
Croup infectious	1/186 (0.5%)		0/187 (0%)		0/97 (0%)
Injury, poisoning and procedural complications
Overdose	0/186 (0%)		0/187 (0%)		1/97 (1%)
Psychiatric disorders
Depressive symptom	0/186 (0%)		0/187 (0%)		1/97 (1%)
Hallucination, auditory	0/186 (0%)		0/187 (0%)		1/97 (1%)
Suicidal ideation	0/186 (0%)		0/187 (0%)		3/97 (3.1%)
Other (Not Including Serious) Adverse Events
	Placebo		Vilazodone		Fluoxetine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	54/186 (29%)		97/187 (51.9%)		27/97 (27.8%)
Gastrointestinal disorders
Nausea	13/186 (7%)		40/187 (21.4%)		6/97 (6.2%)
Vomiting	7/186 (3.8%)		24/187 (12.8%)		4/97 (4.1%)
Diarrhoea	6/186 (3.2%)		16/187 (8.6%)		2/97 (2.1%)
Abdominal pain upper	6/186 (3.2%)		13/187 (7%)		4/97 (4.1%)
Infections and infestations
Upper respiratory tract infection	5/186 (2.7%)		6/187 (3.2%)		5/97 (5.2%)
Nervous system disorders
Headache	31/186 (16.7%)		24/187 (12.8%)		10/97 (10.3%)
Somnolence	4/186 (2.2%)		12/187 (6.4%)		2/97 (2.1%)
Dizziness	5/186 (2.7%)		10/187 (5.3%)		2/97 (2.1%)
Psychiatric disorders
Insomnia	3/186 (1.6%)		10/187 (5.3%)		6/97 (6.2%)

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 are the property of the sponsor. 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 the sponsor and will follow sponsor's standard operating procedures on publications.