Randomized, Double-Blind, Placebo Controlled Study of Vilazodone's Efficacy, Safety, and Biomarkers of Response in Major Depressive Disorder (MDD)

Study Overview
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Brief Summary
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This randomized, double-blind, placebo-controlled, multicenter, 8-week, clinical trial is designed to assess the efficacy and safety of vilazodone and to evaluate genetic biomarkers of treatment response associated with vilazodone use in adult patients diagnosed with MDD by the DSM-IV-TR criteria.

Detailed Description
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This randomized, double-blind, placebo-controlled, multicenter, 8-week, clinical trial is designed to assess the efficacy and safety of vilazodone and to evaluate genetic biomarkers of treatment response associated with vilazodone use in adult patients diagnosed with MDD by the DSM-IV-TR criteria. This study will enroll approximately 470 patients at approximately 10 clinical sites. Safety and efficacy will be assessed at each visit. A DNA sample will be collected and analyzed for response to vilazodone.

Official Title
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A Randomized, Double-blind, Placebo Controlled Study Assessing the Efficacy and Safety of Vilazodone 40 mg qd and Evaluating Genetic Biomarkers Associated With Treatment Response in Patients With Major Depressive Disorder (MDD)

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: vilazodone
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients 18-70 years of age. A diagnosis of MDD, single episode or recurrent, according to DSM-IV-TR (296.2/296.3) with a current Major Depressive Episode of less than two year's duration with a minimum duration of at least 4 weeks. Meets DSM-IV-TR criteria for Major Depressive Disorder. HAM-D score ≥ 22 on the first 17 items of the 21-item HAM-D. HAM-D item 1 (depressed mood) score ≥ 2. Patients must be able to provide written informed consent Patients must be able to speak, read and understand English Exclusion Criteria: Patients with a current (or within 6 months prior to the Screening Visit) Axis I disorder of Post Traumatic Stress Disorder, Eating Disorder, Obsessive Compulsive Disorder. 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 (alcohol or drugs) within 3 months prior to the Screening Visit or substance dependence within 6 months prior to the Screening Visit. Patients who meet criteria for any of the following DSM-IV-TR MDD Specifiers: [a] With Catatonic Features; [b] With Postpartum Onset; [c] With Seasonal Pattern [d]severe with Psychotic Features. Patients who are receiving formal psychotherapy or have had psychotherapy within the 12 weeks prior to the Screening Visit. Patients who have any one of the following: In the month prior to screening, have had active suicidal ideation with some intent to act, without specific plan. In the month prior to screening, have had suicidal ideation with specific plan and intent. Have made a suicide attempt within the 6 months prior to the screening visit. In the opinion of the Investigator, is currently at significant risk of suicide. Patients who have had an inadequate response to at least 2 consecutive antidepressants from different classes given at adequate doses for an adequate duration. Patients who have received electroconvulsive therapy within the 6 months prior to the Screening Visit. Patients currently taking a psychotropic drug. Patients who have taken psychotropic drugs must have discontinued these prior to the Screening Visit. The minimum discontinuation periods are outlined in the study protocol. Patients taking migraine medications with a serotonergic mechanism of action Patients taking CYP3A4 inhibitors such as grapefruit juice, ketoconazole, diltiazem, and macrolide antibiotics or montelukast Patients with known hypersensitivity to SSRIs (selective serotonin reyptake inhibitors) or 5-HT1a agonists. Patients previously treated with vilazodone (also known as SB-659746-A or EMD 68 843). Patients with a history of clinically significant cardiac, renal, neurologic, cerebrovascular, hepatic, hematologic, metabolic or pulmonary disorders. Patients with any serious medical disorder or condition that would, in the investigator's opinion, preclude the administration of study medication. Female patients must not be pregnant, lactating, or planning to become pregnant during the time of study participation. All female patients must be at least 1 year post menopausal or irreversibly surgically sterilized (by hysterectomy, oophorectomy, or bilateral tubal ligation with resection) or determined not to be at risk of pregnancy. Patients with clinically significant abnormalities on electrocardiogram. 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>vilazodone | Drug: vilazodone<br>* titration to 40 mg tablets qd (once a day) for 8 weeks<br>* Other names: EMD68843, SB-659746;|
| Placebo Comparator: 2<br> | Drug: placebo<br>* placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 8 in the MADRS (Montgomery-Asberg Depression Rating Scale) Total Score. | The MADRS is an observer rating scale that has proven to be an efficient and practical measure of depression. The scale was constructed to be sensitive to treatment effects. The change from baseline in MADRS total score has a possible range of -60 to 60 where negative values reflect improvement in depression symptom severity. The method of last observation carried forward was utilized for subjects who discontinued prematurely. | Baseline, Week 1, Week 2, Week 4, Week 6, Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 8 in the HAM-D 17 (17-Item Hamilton Rating Scale for Depression) Total Score | The HAM-D 17 is a 17-item subscale of the HAM-D 21, which is designed to be completed by a trained rater. It is designed for rating depressive symptom severity in patients with a confirmed diagnosis of depressive disorder. The change in HAM-D 17 has a possible range of -52 to 52 with negative values indicating improvment in depression symptom severity. The method of last observation carried forward was utilized for subjects who discontinued prematurely. | Baseline, week 1, week 2, week 4, week 6, week 8 | 
| The CGI-I (Clinician's Global Impression of Improvement) Score at Week 8 | The CGI-I scale measures change from the baseline state at every visit after the baseline visit. It permits a global evaluation of the patient's improvement over time. At the scheduled clinic visits, the clinician assessed the patient's improvement relative to the symptoms at baseline on a CGI-I item using a 7-point scale, where 1 = very much improved and 7 = very much worse. The method of last observation carried forward was utilized for subjects who discontinued prematurely. | Week 1, Week 2, Week 4, Week 6, Week 8 | 
| Change From Baseline to Week 8 in the HAM-A ( Hamilton Anxiety Rating Scale) Total Score | The HAM-A is a rating scale developed to quantify the severity of anxiety. It consists of 14 items, each defined by a series of symptoms. Each item is rated on a 5-point scale, ranging from 0 (not present) to 4 (severe). Change from baseline in the HAM-A total score may range from -52 to 52 with negative value indicating improvement in anxiety symptom severity. The method of last observation carried forward was utilized for subjects who discontinued prematurely. | Baseline, Week 1, Week 2, Week 4, Week 6, Week 8 | 
| MADRS (Montgomery-Asberg Depression Rating Scale) Response Rate at Week 8 | MADRS response was defined as ≥ 50% decrease from baseline in MADRS total score at Week 8. The response rate is the percentage of subjects in each treatment group meeting the criteria for response. The method of last observation carrier forward was utilized for subjects who discontinued prematurely. | Baseline, Week 1, Week 2, Week 4, Week 6, Week 8 | 
| MADRS (Montgomery-Asberg Depression Rating Scale) Remission Rate at Week 8 | MADRS remission was defined as a MADRS total score < 10 at Week 8. The remission rate is the percentage of subjects in each treatment group who met the criteria for remission. The method of last observation carried forward was utilized for subjects who discontinued prematurely. | Baseline, Week 1, Week 2, Week 4, Week 6, Week 8 |