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

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)

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.

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: placebo; Drug: vilazodone

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 481
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Newport Beach, California, United States, 92660
      • Pharmacology Research Institute
  • Florida
    • Bradenton, Florida, United States, 34208
      • Florida Clinical Research Center
  • Georgia
    • Atlanta, Georgia, United States, 30328
      • Atlanta Institute of Medicine and Research
  • Oregon
    • Portland, Oregon, United States, 97210
      • Summit Research Network
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania Department of Psychiatry Mood and Anxiety Disorders
  • Texas
    • Dallas, Texas, United States, 75235
      • Mood Disorders Research Program and Clinic Exchange Park
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah Health Sciences Ctr, Dept of Psychiatry Mood Disorders Clinic
  • Washington
    • Bellevue, Washington, United States, 98004
      • Northwest Clinical Research Center
    • Seattle, Washington, United States, 98104
      • Summit Research Network

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: 2	Drug: placebo; placebo
EXPERIMENTAL: 1; vilazodone	Drug: vilazodone; titration to 40 mg tablets qd (once a day) for 8 weeks; Other Names: EMD68843, SB-659746

What is the study measuring?

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

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Kornstein S, Chang CT, Gommoll CP, Edwards J. Vilazodone efficacy in subgroups of patients with major depressive disorder: a post-hoc analysis of four randomized, double-blind, placebo-controlled trials. Int Clin Psychopharmacol. 2018 Jul;33(4):217-223. doi: 10.1097/YIC.0000000000000217.
• Culpepper L, Mathews M, Ghori R, Edwards J. Clinical relevance of vilazodone treatment in patients with major depressive disorder: categorical improvement in symptoms. Prim Care Companion CNS Disord. 2014;16(1):PCC.13m01571. doi: 10.4088/PCC.13m01571. Epub 2014 Jan 30.
• Jain R, Chen D, Edwards J, Mathews M. Early and sustained improvement with vilazodone in adult patients with major depressive disorder: post hoc analyses of two phase III trials. Curr Med Res Opin. 2014 Feb;30(2):263-70. doi: 10.1185/03007995.2013.855188. Epub 2013 Oct 31.
• Clayton AH, Kennedy SH, Edwards JB, Gallipoli S, Reed CR. The effect of vilazodone on sexual function during the treatment of major depressive disorder. J Sex Med. 2013 Oct;10(10):2465-76. doi: 10.1111/jsm.12004. Epub 2012 Dec 6.
• Reed CR, Kajdasz DK, Whalen H, Athanasiou MC, Gallipoli S, Thase ME. The efficacy profile of vilazodone, a novel antidepressant for the treatment of major depressive disorder. Curr Med Res Opin. 2012 Jan;28(1):27-39. doi: 10.1185/03007995.2011.628303. Epub 2011 Nov 23.
• Khan A, Cutler AJ, Kajdasz DK, Gallipoli S, Athanasiou M, Robinson DS, Whalen H, Reed CR. A randomized, double-blind, placebo-controlled, 8-week study of vilazodone, a serotonergic agent for the treatment of major depressive disorder. J Clin Psychiatry. 2011 Apr;72(4):441-7. doi: 10.4088/JCP.10m06596.

Study record dates

Study Major Dates

• Study Start: March 1, 2008
• Primary Completion (ACTUAL): February 1, 2009
• Study Completion (ACTUAL): March 1, 2009

Study Registration Dates

• First Submitted: May 21, 2008
• First Submitted That Met QC Criteria: May 22, 2008
• First Posted (ESTIMATE): May 23, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): October 27, 2010
• Last Update Submitted That Met QC Criteria: October 5, 2010
• Last Verified: October 1, 2010

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Serotonin 5-HT1 Receptor Agonists; Serotonin Receptor Agonists; Vilazodone Hydrochloride
• Other Study ID Numbers: CLDA-07-DP-02