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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A One Year Open Label Study Assessing the Safety and Tolerability of Vilazodone in Patients With Major Depressive Disorder

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: vilazodone


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vilazodone<br>Vilazodone titrated up to 40 mg/day for 1 year. | Drug: vilazodone<br>* titration to 40 milligrams (mg) every day (qd) for 1 year<br>* Other names: EMD 68843, SB-659746;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 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). | From first dose of study medication and up to 30 days after the last dose of study medication (Up to 13 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change Form Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Score | 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. | Baseline and Weeks 1, 2, 3, 4, 6 ,8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52/Early Termination | 
| Change From Baseline in Clinical Global Impressions - Severity (CGI-S) Score | 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. | Baseline and Weeks 1, 2, 3, 4, 6 ,8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52/Early Termination | 
| Clinical Global Impression - Improvement (CGI-I) Score | 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. | Weeks 1, 2, 3, 4, 6 ,8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52/Early Termination |