A One Year Open Label Study Assessing the Safety and Tolerability of Vilazodone in Patients With Major Depressive Disorder (MDD)

• Sponsor: Forest Laboratories (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00644358
• Collaborator: (none)
• Enrollment: 616
• Locations: 38
• Arm: 1
• Actual Duration (Months): 17
• Patients Per Site: 16.2
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

This open label 52-week clinical trial is designed to assess the safety and tolerability of vilazodone and to analyze genetic markers of response to vilazodone in adult patients diagnosed with MDD. This study will enroll approximately 600 patients.

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder	Drug: vilazodone	Phase 3

Detailed Description

Patients will be enrolled at approximately 40 US investigative sites and receive vilazodone for 52 weeks of open label treatment. Safety measurements will include adverse events, vital signs, laboratory, ophthalmologic exams, Changes in Sexual Function Questionnaire (CSFQ) scale and electrocardiogram (ECG) findings collected over the course of the treatment period. Effectiveness measurements will be done at baseline and each visit until week 52 or end-of-treatment. A deoxyribonucleic acid (DNA) sample will be collected for genetic analysis related to response to vilazodone.

Study Design

• Study Type: Interventional
• Actual Enrollment: 616 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A One Year Open Label Study Assessing the Safety and Tolerability of Vilazodone in Patients With Major Depressive Disorder
• Actual Study Start Date: Dec 31, 2007
• Actual Primary Completion Date: May 31, 2009
• Actual Study Completion Date: May 31, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Vilazodone Vilazodone titrated up to 40 mg/day for 1 year.	Drug: vilazodone; titration to 40 milligrams (mg) every day (qd) for 1 year; Other Names: EMD 68843, SB-659746

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [From first dose of study medication and up to 30 days after the last dose of study medication (Up to 13 months)]

   An Adverse Event (AE) is any untoward medical occurrence in a clinical study participant administered study drug. An AE could, therefore, be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug, whether or not related to the medicinal product. An AE that occurred during the treatment period was defined as a TEAE if the AE was either not present at, or before, the day of the first dose of study medication or was present at, or before, the day of the first dose of study medication and increased in severity during the treatment period. AEs included abnormal clinically significant findings for laboratory parameters, physical examinations, vital signs, weight, electrocardiograms (ECGs), the Change in Sexual Functioning Questionnaire (CSFQ), ophthalmologic exams and the Columbia-Suicide Severity Rating Scale (C-SSRS).

Secondary Outcome Measures

1. Change Form Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Score [Baseline and Weeks 1, 2, 3, 4, 6 ,8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52/Early Termination]

   The MADRS is a clinician-rated scale for assessing depressive symptomatology that had occurred in participants during the week preceding each interview. Participants 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.

2. Change From Baseline in Clinical Global Impressions - Severity (CGI-S) Score [Baseline and Weeks 1, 2, 3, 4, 6 ,8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52/Early Termination]

   The CGI-S is a clinician-rated scale that measures global severity of illness at a given point in time using a 7-point scale where 1=normal, not at all ill, and 7=among the most severely ill. A negative change from Baseline indicates improvement.

3. Clinical Global Impression - Improvement (CGI-I) Score [Weeks 1, 2, 3, 4, 6 ,8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52/Early Termination]

   The CGI-I is a clinician-rated scale for assessing improvement of a patient's condition, using a 7-point scale where 1=very much improved (best) and 7=very much worse.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Males or females 18-70 years of age.

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

• Hamilton Depression Rating Scale (HAM-D) score ≥ 18 on the first 17 items of the 21-item HAM-D at Screening and Baseline Visits.

• Patients must have general ocular health.

Exclusion Criteria:

• Patients with a history of schizophrenia, schizoaffective disorder or bipolar I or II disorder (with a history of hypomanic or manic episodes).

• Patients who meet DSM-IV-TR criteria for substance abuse or dependence within 1 year of the Baseline visit.

• Patients who, in the Investigator's judgment, pose a serious suicidal or homicidal risk or have made a suicide attempt within 6 months prior to Screening Visit.

• Patients who are taking psychotropic drugs. Patients who have taken psychotropic drugs must have discontinued these prior to Screening Visit.

• Patients taking migraine medications with a serotonergic mechanism of action.

• Patients taking Cytochrome P450 3A4 (CYP3A4) inhibitors such as grapefruit juice, ketoconazole, diltiazem, and macrolide antibiotics.

• Patients with a known hypersensitivity to selective serotonin reuptake inhibitors (SSRIs) or 5-hydroxytryptamine 1a (5-HT1a) agonists.

• Patients previously treated with vilazodone.

• Patients taking Chantix or St. John's Wort.

• Presence of significant acute or chronic medical disorders by history or physical exam.

• Patients with a history of seizure disorders.

• Prior history of malignancy if patient has <5 year survival OR completed treatment <1 year prior to enrollment and is currently without evidence of recurrence.

• Skin cancers other than malignant melanoma will be permitted.

• Patients with evidence of other central nervous system disorders including psychosis, delirium, dementia and amnesic disorders.

• Patients with renal impairment or hepatic impairment.

• Patients who are not euthyroid.

• Patients with any serious medical or neurological disorder or condition that make it unlikely that the patient could complete one year of treatment or would otherwise preclude the administration of study medication.

• Female patients must not be pregnant, not lactating, and not planning to become pregnant during the time of study participation. All female patients who are not at least 1 year post menopausal or irreversibly surgically sterilized must be using adequate and reliable contraception throughout the trial.

• Patients with clinically significant ECG abnormalities which, as determined by the investigator, make it unlikely that the patient would complete one year of treatment or would otherwise preclude treatment with vilazodone.

• Patients having clinically significant abnormal laboratory findings.

• Patients with a positive drug screen.

• Patients who, in the opinion of the investigator, would be noncompliant with the visit schedule or study procedures.

• Patients that have taken an investigational drug or participated in an investigational drug trial within the past 30 days.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Collaborative Neuroscience Network, Inc.	Garden Grove	California	United States	92845
2	Affiliated Research Institute	San Diego	California	United States	92108
3	Collaborative Neuroscience Network, Inc	Torrance	California	United States	90502
4	Pacific Clinical Research	Upland	California	United States	91786
5	Radiant Research	Denver	Colorado	United States	80239
6	CNS Clinical Research Group	Coral Springs	Florida	United States	33065
7	Gulfcoast Clinical Research	Fort Myers	Florida	United States	33912
8	Sarkis Clinical Trials	Gainesville	Florida	United States	32607
9	Clinical Neuroscience Solutions, Inc	Jacksonville	Florida	United States	32216
10	Florida Clinical Research Center, LLC	Lady Lake	Florida	United States	32159
11	Clinical Neuroscience Solutions, PA	Orlando	Florida	United States	32806
12	Stedman Clinical Trials	Tampa	Florida	United States	33613
13	Carman Research	Smyrna	Georgia	United States	30080
14	Chicago Research Center	Chicago	Illinois	United States	60634
15	Capstone Clinical Research	Libertyville	Illinois	United States	60048
16	Davis Clinic	Indianapolis	Indiana	United States	46260
17	Vince and Associates Clinical Research	Overland Park	Kansas	United States	66212
18	Capital Clinical Research Associates	Rockville	Maryland	United States	20852
19	Summit Research Network	Farmington	Michigan	United States	48336
20	Radiant Research	Saint Louis	Missouri	United States	63141
21	Radiant Research	Las Vegas	Nevada	United States	89146
22	Bioscience Research, LLC	Mount Kisco	New York	United States	10549
23	Eastside Comprehensive Medical Center	New York	New York	United States	10021
24	The Medical Research Network, LLC	New York	New York	United States	10024
25	North Coast Clinical Trials	Beachwood	Ohio	United States	44122
26	Patient Priority Clinical Sites, LLC	Cincinnati	Ohio	United States	45242
27	North Star Medical Research, LLC	Middleburg Heights	Ohio	United States	44130
28	IPS Research Company	Oklahoma City	Oklahoma	United States	73103
29	Paramount Clinical Research	Bridgeville	Pennsylvania	United States	15017
30	Introspect of Buxmont	Colmar	Pennsylvania	United States	18915
31	Suburban Research Associates	Media	Pennsylvania	United States	19063
32	Clinical Neuroscience Solutions	Memphis	Tennessee	United States	38119
33	FutureSearch Trials	Austin	Texas	United States	78756
34	FutureSearch Trials	Dallas	Texas	United States	75231
35	Croft Group Research Center	San Antonio	Texas	United States	78229
36	Neuropsychiatric Associates	Woodstock	Vermont	United States	05091
37	Neuroscience, Inc.	Herndon	Virginia	United States	20170
38	Dominion Clinical Research	Midlothian	Virginia	United States	23112

Sponsors and Collaborators

• Forest Laboratories

Investigators

• Study Director: Carol R Reed, MD, Forest Laboratories

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Forest Laboratories
• ClinicalTrials.gov Identifier: NCT00644358
• Other Study ID Numbers: CLDA-07-DP-04
• First Posted: Mar 26, 2008
• Last Update Posted: Sep 25, 2017
• Last Verified: Aug 1, 2017

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

Study Results

Participant Flow

Arm/Group Title	Vilazodone
Arm/Group Description	Vilazodone titrated up to 40 milligrams (mg)/day for 1 year.
Period Title: Overall Study
STARTED	616
COMPLETED	254
NOT COMPLETED	362

Baseline Characteristics

Arm/Group Title	Vilazodone
Arm/Group Description	Vilazodone titrated up to 40 mg/day for 1 year.
Overall Participants	599
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	42.8 (12.47)
Sex: Female, Male (Count of Participants)
Female	407 67.9%
Male	192 32.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	54 9%
Not Hispanic or Latino	545 91%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	3 0.5%
Asian	10 1.7%
Native Hawaiian or Other Pacific Islander	3 0.5%
Black or African American	103 17.2%
White	479 80%
More than one race	0 0%
Unknown or Not Reported	1 0.2%
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	168.4 (9.62)

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Description	An Adverse Event (AE) is any untoward medical occurrence in a clinical study participant administered study drug. An AE could, therefore, be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug, whether or not related to the medicinal product. An AE that occurred during the treatment period was defined as a TEAE if the AE was either not present at, or before, the day of the first dose of study medication or was present at, or before, the day of the first dose of study medication and increased in severity during the treatment period. AEs included abnormal clinically significant findings for laboratory parameters, physical examinations, vital signs, weight, electrocardiograms (ECGs), the Change in Sexual Functioning Questionnaire (CSFQ), ophthalmologic exams and the Columbia-Suicide Severity Rating Scale (C-SSRS).
Time Frame	From first dose of study medication and up to 30 days after the last dose of study medication (Up to 13 months)

Outcome Measure Data

Analysis Population Description

Safety population consisted of enrolled participants who took at least 1 dose of study drug and had at least 1 post-baseline safety measurement.

Arm/Group Title	Vilazodone
Arm/Group Description	Vilazodone titrated up to 40 mg/day for 1 year.
Measure Participants	599
Number [Participants]	562 93.8%

2. Secondary Outcome

Title	Change Form Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Score
Description	The MADRS is a clinician-rated scale for assessing depressive symptomatology that had occurred in participants during the week preceding each interview. Participants 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 and Weeks 1, 2, 3, 4, 6 ,8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52/Early Termination

Outcome Measure Data

Analysis Population Description

Effectiveness Population consisted of all participants who took at least one dose, and had at least one post-baseline efficacy endpoint measurement. The number analyzed for each category row is the number of participants with available data at the given time-point.

Arm/Group Title	Vilazodone
Arm/Group Description	Vilazodone titrated up to 40 mg/day for 1 year.
Measure Participants	596
Baseline	29.9 (4.45)
Change from Baseline at Week 1	-4.7 (5.38)
Change from Baseline at Week 2	-9.3 (6.72)
Change from Baseline at Week 3	-13.0 (7.76)
Change from Baseline at Week 4	-14.9 (7.99)
Change from Baseline at Week 6	-17.1 (8.28)
Change from Baseline at Week 8	-18.5 (8.38)
Change from Baseline at Week 12	-19.9 (8.31)
Change from Baseline at Week 16	-20.6 (8.31)
Change from Baseline at Week 20	-21.1 (8.39)
Change from Baseline at Week 24	-21.7 (7.81)
Change from Baseline at Week 28	-21.6 (7.99)
Change from Baseline at Week 32	-21.9 (8.26)
Change from Baseline at Week 36	-22.1 (7.89)
Change from Baseline at Week 40	-22.7 (7.33)
Change from Baseline at Week 44	-21.9 (8.12)
Change from Baseline at Week 48	-22.5 (7.92)
Change from Baseline at Week 52	-22.8 (7.89)
Change from Baseline at Early Termination	-10.9 (9.78)

3. Secondary Outcome

Title	Change From Baseline in Clinical Global Impressions - Severity (CGI-S) Score
Description	The CGI-S is a clinician-rated scale that measures global severity of illness at a given point in time using a 7-point scale where 1=normal, not at all ill, and 7=among the most severely ill. A negative change from Baseline indicates improvement.
Time Frame	Baseline and Weeks 1, 2, 3, 4, 6 ,8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52/Early Termination

Outcome Measure Data

Analysis Population Description

Effectiveness Population consisted of all participants who took at least one dose, and had at least one post-baseline efficacy endpoint measurement. The number analyzed for each category row is the number of participants with available data at the given time-point.

Arm/Group Title	Vilazodone
Arm/Group Description	Vilazodone titrated up to 40 mg/day for 1 year.
Measure Participants	596
Baseline	4.3 (0.52)
Change from Baseline at Week 1	-0.3 (0.57)
Change from Baseline at Week 2	-0.7 (0.83)
Change from Baseline at Week 3	-1.1 (1.04)
Change from Baseline at Week 4	-1.4 (1.12)
Change from Baseline at Week 6	-1.7 (1.18)
Change from Baseline at Week 8	-1.9 (1.21)
Change from Baseline at Week 12	-2.1 (1.18)
Change from Baseline at Week 16	-2.3 (1.13)
Change from Baseline at Week 20	-2.4 (1.15)
Change from Baseline at Week 24	-2.4 (1.09)
Change from Baseline at Week 28	-2.4 (1.09)
Change from Baseline at Week 32	-2.5 (1.11)
Change from Baseline at Week 36	-2.5 (1.13)
Change from Baseline at Week 40	-2.5 (1.05)
Change from Baseline at Week 44	-2.4 (1.12)
Change from Baseline at Week 48	-2.5 (1.08)
Change from Baseline at Week 52	-2.6 (1.13)
Change from Baseline at Early Termination	-1.0 (1.21)

4. Secondary Outcome

Title	Clinical Global Impression - Improvement (CGI-I) Score
Description	The CGI-I is a clinician-rated scale for assessing improvement of a patient's condition, using a 7-point scale where 1=very much improved (best) and 7=very much worse.
Time Frame	Weeks 1, 2, 3, 4, 6 ,8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52/Early Termination

Outcome Measure Data

Analysis Population Description

Effectiveness Population consisted of all participants who took at least one dose, and had at least one post-baseline efficacy endpoint measurement. The number analyzed for each category row is the number of participants with available data at the given time-point.

Arm/Group Title	Vilazodone
Arm/Group Description	Vilazodone titrated up to 40 mg/day for 1 year.
Measure Participants	596
Week 1	3.5 (0.67)
Week 2	3.0 (0.85)
Week 3	2.5 (0.94)
Week 4	2.3 (0.94)
Week 6	2.0 (0.92)
Week 8	1.9 (0.93)
Week 12	1.7 (0.93)
Week 16	1.6 (0.90)
Week 20	1.5 (0.84)
Week 24	1.5 (0.75)
Week 28	1.5 (0.79)
Week 32	1.5 (0.83)
Week 36	1.5 (0.78)
Week 40	1.4 (0.74)
Week 44	1.5 (0.86)
Week 48	1.4 (0.74)
Week 52	1.4 (0.75)
Early Termination	2.9 (1.18)

Adverse Events

Time Frame	From first dose of study medication and up to 30 days after the last dose of study medication (Up to 13 months)
Arm/Group Title	Vilazodone
Arm/Group Description	Vilazodone titrated up to 40 mg/day for 1 year.
All Cause Mortality
	Vilazodone
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Vilazodone
	Affected / at Risk (%)	# Events
Total	23/599 (3.8%)
Gastrointestinal disorders
Duodenal stenosis	1/599 (0.2%)
General disorders
Chest discomfort	1/599 (0.2%)
Chest pain	1/599 (0.2%)
Pyrexia	1/599 (0.2%)
Hepatobiliary disorders
Cholecystitis	1/599 (0.2%)
Gallbladder disorder	1/599 (0.2%)
Infections and infestations
Abdominal wall abscess	1/599 (0.2%)
Enterocolitis infectious	1/599 (0.2%)
Gastroenteritis	1/599 (0.2%)
Pneumonia	2/599 (0.3%)
Injury, poisoning and procedural complications
Overdose	1/599 (0.2%)
Skin laceration	1/599 (0.2%)
Investigations
Bronchoscopy	1/599 (0.2%)
Metabolism and nutrition disorders
Dehydration	1/599 (0.2%)
Hypokalaemia	1/599 (0.2%)
Hyponatraemia	1/599 (0.2%)
Obesity	1/599 (0.2%)
Nervous system disorders
Serotonin syndrome	1/599 (0.2%)
Syncope	1/599 (0.2%)
Transient ischaemic attack	1/599 (0.2%)
Pregnancy, puerperium and perinatal conditions
Ruptured ectopic pregnancy	1/599 (0.2%)
Psychiatric disorders
Panic attack	1/599 (0.2%)
Suicidal ideation	1/599 (0.2%)
Suicide attempt	1/599 (0.2%)
Renal and urinary disorders
Renal failure acute	1/599 (0.2%)
Reproductive system and breast disorders
Endometriosis	1/599 (0.2%)
Menometrorrhagia	1/599 (0.2%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	1/599 (0.2%)
Chronic obstructive pulmonary disease	1/599 (0.2%)
Pulmonary embolism	1/599 (0.2%)
Sleep apnoea syndrome	1/599 (0.2%)
Vascular disorders
Deep vein thrombosis	1/599 (0.2%)
Other (Not Including Serious) Adverse Events
	Vilazodone
	Affected / at Risk (%)	# Events
Total	497/599 (83%)
Gastrointestinal disorders
Diarrhoea	214/599 (35.7%)
Dry mouth	66/599 (11%)
Nausea	189/599 (31.6%)
Vomiting	44/599 (7.3%)
General disorders
Fatigue	46/599 (7.7%)
Infections and infestations
Nasopharyngitis	45/599 (7.5%)
Upper respiratory tract infection	82/599 (13.7%)
Urinary tract infection	35/599 (5.8%)
Investigations
Weight increased	57/599 (9.5%)
Metabolism and nutrition disorders
Increased appetite	54/599 (9%)
Musculoskeletal and connective tissue disorders
Back pain	33/599 (5.5%)
Nervous system disorders
Dizziness	64/599 (10.7%)
Headache	120/599 (20%)
Somnolence	64/599 (10.7%)
Psychiatric disorders
Abnormal dreams	62/599 (10.4%)
Anxiety	36/599 (6%)
Insomnia	78/599 (13%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

A disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 90 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.