Clinical trial NCT00683592: Randomized, Double-Blind, Placebo Controlled Study of Vilazodone's Efficacy, Safety, and Biomarkers of Response in Major Depressive Disorder (MDD)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Major Depressive Disorder
Lead sponsor: Forest Laboratories
Sponsor class: INDUSTRY
First posted: 2008-05-23
Enrollment: 481
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change From Baseline to Week 8 in the MADRS (Montgomery-Asberg Depression Rating Scale) Total Score.
timeFrame: Baseline, Week 1, Week 2, Week 4, Week 6, Week 8
Secondary outcomes:
measure: Change From Baseline to Week 8 in the HAM-D 17 (17-Item Hamilton Rating Scale for Depression) Total Score
timeFrame: Baseline, week 1, week 2, week 4, week 6, week 8
measure: The CGI-I (Clinician's Global Impression of Improvement) Score at Week 8
timeFrame: Week 1, Week 2, Week 4, Week 6, Week 8
measure: Change From Baseline to Week 8 in the HAM-A ( Hamilton Anxiety Rating Scale) Total Score
timeFrame: Baseline, Week 1, Week 2, Week 4, Week 6, Week 8
measure: MADRS (Montgomery-Asberg Depression Rating Scale) Response Rate at Week 8
timeFrame: Baseline, Week 1, Week 2, Week 4, Week 6, Week 8
measure: MADRS (Montgomery-Asberg Depression Rating Scale) Remission Rate at Week 8
timeFrame: Baseline, Week 1, Week 2, Week 4, Week 6, Week 8
Other outcomes:
Locations:
city: Newport Beach
country: United States
facility: Pharmacology Research Institute
state: California
city: Bradenton
country: United States
facility: Florida Clinical Research Center
state: Florida
city: Atlanta
country: United States
facility: Atlanta Institute of Medicine and Research
state: Georgia
city: Portland
country: United States
facility: Summit Research Network
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania Department of Psychiatry Mood and Anxiety Disorders
state: Pennsylvania
city: Dallas
country: United States
facility: Mood Disorders Research Program and Clinic Exchange Park
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Health Sciences Ctr, Dept of Psychiatry Mood Disorders Clinic
state: Utah
city: Bellevue
country: United States
facility: Northwest Clinical Research Center
state: Washington
city: Seattle
country: United States
facility: Summit Research Network
state: Washington
Study officials:
affiliation: Forest Laboratories
name: Carol R Reed, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.