A Study of Vilazodone in Pediatric Patients With Major Depressive Disorder (VLZ-MD-23)

• ClinicalTrials.gov Identifier: NCT02436239
• Recruitment Status: Completed
• First Posted: May 6, 2015
• Results First Posted: September 11, 2019
• Last Update Posted: September 11, 2019
• Sponsor: Forest Laboratories
• Information provided by (Responsible Party): Forest Laboratories

• Study Type: Interventional
• Study Design: Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Major Depressive Disorder
• Intervention: Drug: Vilazodone
• Enrollment: 330

Participant Flow

Recruitment Details
Pre-assignment Details	Patients who completed lead-in study VLZ-MD-22 (NCT02372799) had already completed a down-taper period at the end of study VLZ-MD-22 and were not required to undergo a washout period in VLZ-MD-23. For de novo patients, the screening/washout period was generally 1 week prior to Baseline.

Arm/Group Title	Placebo/Vilazodone	Vilazodone/Vilazodone	Fluoxetine/Vilazodone	De Novo/Vilazodone
Arm/Group Description	Participants who received placebo during the lead in study, VLZ-MD-22, were given vilazodone tablets once daily, oral administration.	Participants who received vilazodone during the lead in study, VLZ-MD-22, were given vilazodone tablets once daily, oral administration.	Participants who received Fluoxetine during the lead in study, VLZ-MD-22, were given vilazodone tablets once daily, oral administration.	Newly enrolled participants received vilazodone tablets once daily, oral administration.
Period Title: Open-Lable Treatment Period
Started	122	131	65	12
Completed	89	97	38	7
Not Completed	33	34	27	5
Reason Not Completed
Adverse Event	12	3	4	2
Lack of Efficacy	1	6	6	1
Withdrawal by Subject	10	15	9	0
Lost to Follow-up	4	2	4	1
Protocol Violation	0	1	1	0
Noncompliance with Study Drug	5	6	3	1
Other Reason	1	1	0	0
Period Title: Down-Taper Period
Started	90 [1]	103 [1]	44 [1]	6 [2]
Completed	86	99	43	4
Not Completed	4	4	1	2
Reason Not Completed
Withdrawal by Subject	4	4	1	2
[1] Enrollment permitted for participants who had not completed previous open-label treatment period.; [2] One participant who completed the open-label treatment period did not enter the down-taper period.

Baseline Characteristics

Arm/Group Title		Placebo/Vilazodone	Vilazodone/Vilazodone	Fluoxetine/Vilazodone	De Novo/Vilazodone	Total
Arm/Group Description		Participants who received placebo during the lead in study, VLZ-MD-22, were given vilazodone tablets once daily, oral administration.	Participants who received vilazodone during the lead in study, VLZ-MD-22, were given vilazodone tablets once daily, oral administration.	Participants who received Fluoxetine during the lead in study, VLZ-MD-22, were given vilazodone tablets once daily, oral administration.	Newly enrolled participants received vilazodone tablets once daily, oral administration.	Total of all reporting groups
Overall Number of Baseline Participants		122	131	65	12	330
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	122 participants	131 participants	65 participants	12 participants	330 participants
		13.2 (2.9)	13.3 (2.8)	13.2 (2.8)	13.0 (2.9)	13.3 (2.9)
Age, Customized; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	122 participants	131 participants	65 participants	12 participants	330 participants
	Age 7-11 Years	37 30.3%	35 26.7%	19 29.2%	4 33.3%	95 28.8%
	Age 12-17 Years	83 68.0%	93 71.0%	46 70.8%	8 66.7%	230 69.7%
	Age 18 Years	2 1.6%	3 2.3%	0 0.0%	0 0.0%	5 1.5%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	122 participants	131 participants	65 participants	12 participants	330 participants
	Female	68 55.7%	89 67.9%	33 50.8%	7 58.3%	197 59.7%
	Male	54 44.3%	42 32.1%	32 49.2%	5 41.7%	133 40.3%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	122 participants	131 participants	65 participants	12 participants	330 participants
	Hispanic or Latino	16 13.1%	16 12.2%	8 12.3%	2 16.7%	42 12.7%
	Not Hispanic or Latino	106 86.9%	115 87.8%	57 87.7%	10 83.3%	288 87.3%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	122 participants	131 participants	65 participants	12 participants	330 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Asian	5 4.1%	1 0.8%	1 1.5%	0 0.0%	7 2.1%
	Native Hawaiian or Other Pacific Islander	0 0.0%	2 1.5%	0 0.0%	0 0.0%	2 0.6%
	Black or African American	32 26.2%	40 30.5%	20 30.8%	1 8.3%	93 28.2%
	White	82 67.2%	84 64.1%	42 64.6%	11 91.7%	219 66.4%
	More than one race	3 2.5%	4 3.1%	2 3.1%	0 0.0%	9 2.7%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Weight; Mean (Standard Deviation); Unit of measure: Kg
	Number Analyzed	122 participants	131 participants	65 participants	12 participants	330 participants
		57.98 (23.54)	62.67 (25.26)	59.36 (18.93)	60.34 (17.87)	60.17 (23.26)
Body Mass Index (BMI); Mean (Standard Deviation); Unit of measure: Kg/m^2
	Number Analyzed	122 participants	131 participants	65 participants	12 participants	330 participants
		22.73 (6.59)	24.75 (7.96)	23.30 (5.37)	23.90 (6.20)	23.69 (6.98)
CDRS-R total score [1] [2]; Mean (Standard Deviation); Unit of measure: Units on a scale
	Number Analyzed	121 participants	130 participants	63 participants	11 participants	325 participants
		55.7 (9.6)	59.3 (9.5)	57.8 (8.7)	59.7 (9.1)	58.4 (9.3)
		[1] Measure 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.; [2] Measure Analysis Population Description: The CDRS-R total score is provided at baseline for the Intent to Treat study population, which comprises the 325 patients in the Safety Population who had a baseline and at least 1 postbaseline assessment of the CDRS-R total score.
CGI-S score [1] [2]; Mean (Standard Deviation); Unit of measure: Units on a scale
	Number Analyzed	121 participants	130 participants	63 participants	11 participants	325 participants
		4.6 (0.6)	4.7 (0.7)	4.6 (0.6)	4.2 (0.4)	4.6 (0.6)
		[1] Measure 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.; [2] Measure Analysis Population Description: The CGI-S score is provided at baseline for the Intent to Treat study population, which comprises the 325 patients in the Safety Population who had a baseline and at least 1 postbaseline assessment of the CDRS-R total score.

Outcome Measures

1. Primary Outcome

Title	Number of Participants to Experience a Treatment Emergent Adverse Event (TEAE)
Description	The number of Participants who experienced a treatment emergent adverse events during the 27 week period from screening to the end of the open-label treatment period
Time Frame	Visit 1 (Week -1) to up to Visit 16 (Week 26)

Outcome Measure Data

Analysis Population Description

The Safety Population consisted of the 330 participants who took at least 1 dose of open-label investigational product.

Arm/Group Title	Placebo/Vilazodone	Vilazodone/Vilazodone	Fluoxetine/Vilazodone	De Novo/Vilazodone
Arm/Group Description:	Participants who received placebo during the lead in study, VLZ-MD-22, were given vilazodone tablets once daily, oral administration.	Participants who received vilazodone during the lead in study, VLZ-MD-22, were given vilazodone tablets once daily, oral administration.	Participants who received Fluoxetine during the lead in study, VLZ-MD-22, were given vilazodone tablets once daily, oral administration.	Newly enrolled participants received vilazodone tablets once daily, oral administration.
Overall Number of Participants Analyzed	122	131	65	12
Measure Type: Count of Participants; Unit of Measure: Participants
	90 73.8%	89 67.9%	48 73.8%	10 83.3%

2. Secondary Outcome

Title	Change From Baseline in the 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	Baseline (Week 0) to Week 26

Outcome Measure Data

Analysis Population Description

The Change From Baseline in the CDRS-R Total Score was assessed in the Intent to Treat study population, comprised of the 325 patients in the Safety Population who had a baseline and at least 1 postbaseline assessment of the CDRS-R total score.

Arm/Group Title	Placebo/Vilazodone	Vilazodone/Vilazodone	Fluoxetine/Vilazodone	De Novo/Vilazodone
Arm/Group Description:	Participants who received placebo during the lead in study, VLZ-MD-22, were given vilazodone tablets once daily, oral administration.	Participants who received vilazodone during the lead in study, VLZ-MD-22, were given vilazodone tablets once daily, oral administration.	Participants who received Fluoxetine during the lead in study, VLZ-MD-22, were given vilazodone tablets once daily, oral administration.	Newly enrolled participants received vilazodone tablets once daily, oral administration.
Overall Number of Participants Analyzed	121	130	63	11
Mean (Standard Deviation); Unit of Measure: units on a scale
	-29.2 (11.9)	-30.1 (12.2)	-29.4 (12.2)	-24.5 (10.3)

3. Secondary Outcome

Title	Change From Baseline in the 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	Baseline (Week 0) to Week 26

Outcome Measure Data

Analysis Population Description

The CGI-S was assessed in the Intent to Treat study population, comprised of the 325 patients in the Safety Population who had a baseline and at least 1 postbaseline assessment of the CDRS-R total score.

Arm/Group Title	Placebo/Vilazodone	Vilazodone/Vilazodone	Fluoxetine/Vilazodone	De Novo/Vilazodone
Arm/Group Description:	Participants who received placebo during the lead in study, VLZ-MD-22, were given vilazodone tablets once daily, oral administration.	Participants who received vilazodone during the lead in study, VLZ-MD-22, were given vilazodone tablets once daily, oral administration.	Participants who received Fluoxetine during the lead in study, VLZ-MD-22, were given vilazodone tablets once daily, oral administration.	Newly enrolled participants received vilazodone tablets once daily, oral administration.
Overall Number of Participants Analyzed	121	130	63	11
Mean (Standard Deviation); Unit of Measure: units on a scale
	-2.5 (1.3)	-2.6 (1.4)	-2.5 (1.4)	-1.7 (1.2)

4. Secondary Outcome

Title	Change From Baseline in Clinical Global Impressions-Improvement (CGI-I)
Description	The Clinical Global Impressions-Improvement is a clinician-rated instrument that was used to rate total improvement or worsening of mental illness, regardless of whether the Investigator considered it to be a result of treatment with the investigational product. The CGI-I was used to rate the patient’s improvement on a scale from 1 to 7, with 1 indicating that the patient was very much improved (with a score of 4 indicating no change) and 7 indicating the patient was very much worse.
Time Frame	Baseline (Week 0) to Week 26

Outcome Measure Data

Analysis Population Description

The CGI-I was assessed in the Intent to Treat study population, comprised of the 325 patients in the Safety Population who had a baseline and at least 1 postbaseline assessment of the CDRS-R total score.

Arm/Group Title	Placebo/Vilazodone	Vilazodone/Vilazodone	Fluoxetine/Vilazodone	De Novo/Vilazodone
Arm/Group Description:	Participants who received placebo during the lead in study, VLZ-MD-22, were given vilazodone tablets once daily, oral administration.	Participants who received vilazodone during the lead in study, VLZ-MD-22, were given vilazodone tablets once daily, oral administration.	Participants who received Fluoxetine during the lead in study, VLZ-MD-22, were given vilazodone tablets once daily, oral administration.	Newly enrolled participants received vilazodone tablets once daily, oral administration.
Overall Number of Participants Analyzed	121	130	63	11
Mean (Standard Deviation); Unit of Measure: units on a scale
	2.1 (1.2)	2.0 (1.3)	2.0 (1.2)	2.2 (1.2)

Adverse Events

Time Frame	Adverse event data was collected for up to 28 weeks, which consists of the screening visit (1 week), the 26 week open label treatment period and during the 1 week down taper period.
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Placebo/Vilazodone	Vilazodone/Vilazodone	Fluoxetine/Vilazodone	De Novo/Vilazodone
Arm/Group Description	Participants who received placebo during the lead in study, VLZ-MD-22, were given vilazodone tablets once daily, oral administration.	Participants who received vilazodone during the lead in study, VLZ-MD-22, were given vilazodone tablets once daily, oral administration.	Participants who received Fluoxetine during the lead in study, VLZ-MD-22, were given vilazodone tablets once daily, oral administration.	Newly enrolled participants received vilazodone tablets once daily, oral administration.
All-Cause Mortality
	Placebo/Vilazodone	Vilazodone/Vilazodone	Fluoxetine/Vilazodone	De Novo/Vilazodone
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/122 (0.00%)	0/131 (0.00%)	1/65 (1.54%)	0/12 (0.00%)
Serious Adverse Events
	Placebo/Vilazodone	Vilazodone/Vilazodone	Fluoxetine/Vilazodone	De Novo/Vilazodone
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	6/122 (4.92%)	0/131 (0.00%)	1/65 (1.54%)	0/12 (0.00%)
Infections and infestations
Appendicitis † 1	1/122 (0.82%)	0/131 (0.00%)	0/65 (0.00%)	0/12 (0.00%)
Injury, poisoning and procedural complications
Gun Shot Wound † 1	0/122 (0.00%)	0/131 (0.00%)	1/65 (1.54%)	0/12 (0.00%)
Psychiatric disorders
Suicidal ideation † 1	2/122 (1.64%)	0/131 (0.00%)	0/65 (0.00%)	0/12 (0.00%)
Abnormal behaviour † 1	1/122 (0.82%)	0/131 (0.00%)	0/65 (0.00%)	0/12 (0.00%)
Aggression † 1	1/122 (0.82%)	0/131 (0.00%)	0/65 (0.00%)	0/12 (0.00%)
Suicide attempt † 1	1/122 (0.82%)	0/131 (0.00%)	0/65 (0.00%)	0/12 (0.00%)
1 Term from vocabulary, MedDRA 21.0; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Placebo/Vilazodone	Vilazodone/Vilazodone	Fluoxetine/Vilazodone	De Novo/Vilazodone
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	79/122 (64.75%)	81/131 (61.83%)	41/65 (63.08%)	10/12 (83.33%)
Ear and labyrinth disorders
Ear Pain † 1	0/122 (0.00%)	1/131 (0.76%)	0/65 (0.00%)	2/12 (16.67%)
Gastrointestinal disorders
Nausea † 1	27/122 (22.13%)	16/131 (12.21%)	8/65 (12.31%)	2/12 (16.67%)
Vomiting † 1	15/122 (12.30%)	8/131 (6.11%)	3/65 (4.62%)	0/12 (0.00%)
Abdominal pain upper † 1	12/122 (9.84%)	6/131 (4.58%)	4/65 (6.15%)	0/12 (0.00%)
Infections and infestations
Nasopharyngitis † 1	5/122 (4.10%)	11/131 (8.40%)	2/65 (3.08%)	0/12 (0.00%)
Gastroenteritis † 1	6/122 (4.92%)	3/131 (2.29%)	3/65 (4.62%)	1/12 (8.33%)
Sinusitis † 1	1/122 (0.82%)	5/131 (3.82%)	2/65 (3.08%)	1/12 (8.33%)
Investigations
Weight increased † 1	7/122 (5.74%)	15/131 (11.45%)	4/65 (6.15%)	1/12 (8.33%)
Nervous system disorders
Headache † 1	21/122 (17.21%)	28/131 (21.37%)	8/65 (12.31%)	2/12 (16.67%)
Dizziness † 1	3/122 (2.46%)	9/131 (6.87%)	4/65 (6.15%)	0/12 (0.00%)
Migraine † 1	3/122 (2.46%)	3/131 (2.29%)	1/65 (1.54%)	1/12 (8.33%)
Syncope † 1	0/122 (0.00%)	0/131 (0.00%)	0/65 (0.00%)	2/12 (16.67%)
Amnesia † 1	0/122 (0.00%)	0/131 (0.00%)	0/65 (0.00%)	1/12 (8.33%)
Psychiatric disorders
Insomnia † 1	13/122 (10.66%)	11/131 (8.40%)	2/65 (3.08%)	0/12 (0.00%)
Irritability † 1	4/122 (3.28%)	3/131 (2.29%)	0/65 (0.00%)	1/12 (8.33%)
Agitation † 1	0/122 (0.00%)	2/131 (1.53%)	0/65 (0.00%)	1/12 (8.33%)
Respiratory, thoracic and mediastinal disorders
Dysmenorrhea † 1	3/122 (2.46%)	4/131 (3.05%)	3/65 (4.62%)	0/12 (0.00%)
1 Term from vocabulary, MedDRA 21.0; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

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.

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.

Results Point of Contact

• Name/Title: Armin Szegedi, MD, PhD, Vice President CNS Clinical Development
• Organization: Allergan
• Phone: 714-246-4500
• EMail: IR-CTRegistration@allergan.com

• Responsible Party: Forest Laboratories
• ClinicalTrials.gov Identifier: NCT02436239 History of Changes
• Other Study ID Numbers: VLZ-MD-23
• First Submitted: April 28, 2015
• First Posted: May 6, 2015
• Results First Submitted: July 23, 2019
• Results First Posted: September 11, 2019
• Last Update Posted: September 11, 2019