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Efficacy and Safety Study of Low-Dose Ondansetron For Adjunctive Therapy In Adult Patients With Obsessive-Compulsive Disorder

Information source: Transcept Pharmaceuticals
Information obtained from ClinicalTrials.gov on December 08, 2011
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Obsessive-compulsive Disorder

Intervention: Ondansetron (Drug); Placebo (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: Transcept Pharmaceuticals

Official(s) and/or principal investigator(s):
Eric Hollander, MD, Study Chair, Affiliation: Montefiore Medical Center, Bronx, NY

Summary

This study is to assess the efficacy and safety of two doses of ondansetron (0. 5 mg and 0. 75 mg) relative to placebo when administered twice daily as adjunctive therapy for adult patients with Obsessive-Compulsive Disorder (OCD) who have not adequately responded to treatment with a serotonin reuptake inhibitor (SRI).

Clinical Details

Official title: A Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study To Evaluate The Efficacy And Safety Of Low-Dose Ondansetron For Adjunctive Therapy In Adult Patients With Obsessive-Compulsive Disorder Who Have Not Adequately Responded To Treatment With A Serotonin Reuptake Inhibitor

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Primary outcome:

Core Period: Change from baseline in the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) total at Month 3 score

Extension Period: Participants with Safety Adverse Experiences

Secondary outcome:

Core Period: Participants Considered Responders as Measured by the Clinical Global Impression-Improvement (CGI-I) Score

Core Period: Change from Baseline in the Clinical Global Impression-Severity (CGI-S) Score at Month 3

Core Period: Change from Baseline in the Sheehan Disability Scale (SDS) Score at Month 3

Detailed description: This is a multi-center, randomized, double-blind, placebo-controlled, parallel-group study.

A sufficient number of patients will be screened to obtain approximately 150 patients randomized to the double-blind portion of the study. This study will consist of at least 6 weeks of retrospectively documented SRI treatment (prior to screening), 6 weeks of prospective SRI treatment after screening (run-in) but prior to randomization, and 12 weeks of double-blind treatment with study drug (ondansetron 0. 5 mg twice a day, ondansetron 0. 75 mg twice a day or placebo twice a day).

All patients will have been maintained on a single SRI at the same dose throughout the retrospective 6-week period and will continue the same SRI at the same dose throughout the run-in and double-blind treatment periods.

The 12-week randomized, double-blind, placebo-controlled, parallel-group study will be the "core period" for purposes of efficacy and short-term safety assessment. Patients completing all 12 weeks of the core period will be offered an opportunity to participate in an "extension period" where they will continue to receive treatment under double-blind conditions for up to 12 months following the core period.

Treatment assignment in the extension period will be as follows: responders will continue on the same double-blind treatment to which they were assigned in the core period (ondansetron 0. 5 mg twice a day, ondansetron 0. 75 mg twice a day, or placebo twice a day); non-responders will be reassigned to continuing treatment according to their prior treatment assignment in the core period (those who received placebo will be assigned to ondansetron 0. 5 mg twice a day, those who received ondansetron 0. 5 mg twice a day will be assigned to ondansetron 0. 75 mg twice a day, and those who received ondansetron 0. 75 mg twice a day will continue receiving ondansetron 0. 75 mg twice a day).

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Core period: Inclusion criteria for entry in prospective serotonin reuptake inhibitor (SRI) period (screening):

- Male or female adults 18 years of age or older

- Able to understand the study and provide informed consent

- Subjects who are fluent in English and/or Spanish (speaking, writing, and reading)

- Willing and able to comply with the requirements of the protocol and follow

directions from the clinic staff

- Body mass index (BMI) ≥18 and ≤ 40 kg/m^2 (wearing indoor clothing without shoes)

- For female patients only: Female patients will be included if they are

post-menopausal for at least two years or sterilized, or if they are of childbearing potential, they are not breastfeeding, their pregnancy test is negative, they have no intention of becoming pregnant during the course of the study, and are using adequate contraceptive drugs or devices. Medically acceptable methods of contraception that may be used by the patient and/or her partner are: oral contraceptives, progestin injection or implants, condom with spermicide, diaphragm with spermicide, IUD, vaginal spermicidal suppository, surgical sterilization or abstinence. Females using oral contraception must have started using the medication at least 8 weeks prior to screening. Surgical sterilization must have occurred at least 6 weeks prior to screening.

- Documented diagnosis of Obsessive-Compulsive Disorder (OCD) as defined by the

Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) criteria

- At screening, documented history of stable and current regimen of one of the

following five serotonin reuptake inhibitor (SRI) for at least 6 weeks prior to screening at the minimum daily dosage listed:

- clomipramine (Anafranil®) 150 mg

- fluvoxamine (Luvox®) 200 mg or fluvoxamine CR (Luvox CR®) 200 mg

- fluoxetine (Prozac®) 40 mg

- paroxetine (Paxil®) 40 mg (does not include paroxetine CR (Paxil CR®))

- sertraline (Zoloft®) 100 mg

- Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) score of ≥ 24

- Hamilton Depression Rating Scale (HAM-D) score of < 20

Inclusion criteria for randomization to double-blind treatment period:

- During run-in, documented use of stable and current regimen of one of the following

five serotonin reuptake inhibitor (SRI) for at least 6 weeks prior to screening at the minimum daily dosage listed:

- clomipramine (Anafranil®) 150 mg

- fluvoxamine (Luvox®) 200 mg or fluvoxamine CR (Luvox CR®) 200 mg

- fluoxetine (Prozac®) 40 mg

- paroxetine (Paxil®) 40 mg (does not include paroxetine CR (Paxil CR®))

- sertraline (Zoloft®) 100 mg

- Demonstrated failure to adequately respond to serotonin reuptake inhibitor (SRI)

treatment, defined by the following 2 criteria after 6 weeks of prospective treatment:

- Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) score ≥ 21

- Less than 25% improvement in Yale-Brown Obsessive-Compulsive Scale (Y-BOCS)

score from Week - 6 (screening)

- Hamilton Depression Rating Scale (HAM-D) score of ≤ 16

Extension Period - Inclusion criteria for randomization to double-blind extension

treatment period:

- Completing 12 weeks of treatment in the double-blind core period

- Demonstrating compliance in the judgment of the investigator, with both the SRI and

study drug as prescribed.

Core Period Exclusion Criteria:

- Presence of significant medical illnesses such as, but not restricted to,

cardiovascular, (including congestive heart failure and bradyarrhythmias), endocrine or intestinal disorders that would interfere with the conduct of the study

- History of significant head injury, other significant brain trauma, or seizure

disorder (not including a single childhood febrile seizure)

- Clinically significant abnormal laboratory findings. Presence of electrolyte

abnormalities will be exclusionary.

- Clinically significant abnormal findings on electrocardiogram (ECG). Diagnosis of

congenital long QT syndrome will be exclusionary.

- Clinically significant abnormal findings on physical examination

- Positive pregnancy test

- Subjects who intend to donate blood or blood components while receiving study drug or

within 1 month of the completion of treatment

- Hoarding as the primary Obsessive-Compulsive Disorder (OCD) symptom (secondary

hoarding will be allowed)

- Obsessive-compulsive spectrum disorder as a primary disorder (secondary

obsessive-compulsive spectrum disorders will be allowed)

- Requiring active behavioral therapy during the study period (run-in and treatment

periods). Patients with a history of behavioral therapy may be enrolled as long as they will not be actively engaged in behavioral therapy during the study. However, booster sessions, occurring no more than quarterly (before and after the core study), are allowed. Supportive and other forms of psychotherapy will be permitted during the study as long as the patient has been engaged in such therapy for at least 8 weeks prior to study enrollment and there are no changes during the study.

- A history of substance dependence or drug or substance abuse, including alcohol

abuse, within the past 12 months. A history of nicotine dependence will not be considered an exclusion criterion.

- Mental retardation or an IQ less than 70

- The following comorbid psychiatric conditions identified by current or past medical

history or as a result of the Mini-International Neuropsychiatric Interview (MINI) or Structured Clinical Interview for DSM-IV-TR Axis II Personality Disorders (SCID-II) psychiatric interviews will be excluded:

- Schizophrenia or other psychotic disorders

- Schizotypal personality disorder

- Bipolar disorder

- Gilles de la Tourette syndrome

- Autism and autistic spectrum disorders

- Eating disorders

- Combat-related post-traumatic stress disorder

- Other comorbid anxiety disorders will be permitted if the severity will not

interfere with study participation.

- Subjects who are believed to have suicidal or homicidal risk (i. e., after an

assessment by a qualified mental health professional if the C-SSRS screening assessment warranted a suicidal risk assessment interview), or with a history of suicidality in the previous 3 months

- Taking trazodone or other medicinal products that have been associated with

prolongation of the QT/QTc interval.

- Taking concomitant antipsychotic drugs, lithium, carbamazepine, oxcarbazepine,

phenytoin, anti-anxiety drugs (other than the current SRI for treatment of OCD), or benzodiazepines prescribed for the treatment of anxiety. PRN use of FDA-approved benzodiazepine or non-benzodiazepine hypnotics will be allowed. In addition, the following 3 benzodiazepines will be allowed, provided that patients have been taking them only at bedtime as a sleep aid for at least 12 weeks at the maximum doses noted below:

- clonazepam (Klonopin®) up to 1 mg

- diazepam (Valium®) up to 5 mg

- lorazepam (Ativan®) up to 1 mg

- Taking more than one SRI at the time of screening or at any time in the previous 8

weeks

- A history of having failed more than 2 prior treatments, not including their current

course of treatment, with serotonin reuptake inhibitors (SRIs), including clomipramine and selective serotonin reuptake inhibitors (SSRIs), or serotonin-norepinephrine reuptake inhibitors (SNRIs) may only be considered after consultation with the medical monitor. Failure is defined as inadequate response, in the judgment of the treating physician, to an adequate dose of SRIs or SNRIs taken for at least 8 weeks.

- Taking any antidepressant drugs (including St. John's Wort), at the time of screening

or at any time in the previous 8 weeks, other than the SRI identified in the retrospective and screening periods

- Likely to use triptans at any time during the run-in or double-blind portion of the

trial

Locations and Contacts

Southwestern Research, Inc., Beverly Hills, California 90210, United States; Recruiting
John Murphy, MD, Email: dmaag@435.com

Sun Valley Research Center, Imperial, California 92251, United States; Recruiting
Alvaro Camacho, MD, Email: acamacho@sunvalleyb.com

Pacific Institute for Medical Research, Los Angeles, California 90024, United States; Recruiting
Tanja Vapnik, Email: tvapnik.pimr@verizon.net

Cedars-Sinai Medical Center, Los Angeles, California 90048, United States; Recruiting
Jonathan Shaywitz, MD, Email: Jonathan.Shaywitz@cshs.org

Compass Research, LLC, Orlando, Florida 32806, United States; Recruiting
James McDonough, MD, Email: drmcdonough@compassresearch.org

University of South Florida, St. Petersburg, Florida 33701, United States; Recruiting
Tanya Murphy, MD, Email: tmurphy@health.usf.edu

Emory University, Atlanta, Georgia 30306, United States; Recruiting
Barbara Rothbaum, PhD, Email: brothba@emory.edu

Carman Research, Smyrna, Georgia 30080, United States; Recruiting
Nathan Shapira, MD, PhD, Email: nas@carmanresearch.com

McLean Hospital, Belmont, Massachusetts 02478, United States; Recruiting
Brian Brennan, MD, Email: bbrennan@partners.org

Ambulatory Research Center, Dept of Psychiatry, Minneapolis, Minnesota 55454, United States; Recruiting
Jon Grant, MD, JD, MPH, Email: grant045@umn.edu

Global Medical Institutes, LLC; Princeton Medical Institute, Princeton, New Jersey 08540, United States; Recruiting
Jeffrey Apter, Email: jtapter@gminstitutes.com

Montefiore Medical Center, Child Psychiatry Annex, Bronx, New York 10467, United States; Recruiting
Eric Hollander, MD, Email: ehollan@montefiore.org

Biobehavioral Institute, Hofstra, Great Neck, New York 11021, United States; Recruiting
Fugen Neziroglu, PhD, Email: neziroglu@aol.com

Columbia University Medical Center NYS Psychiatric Institute, New York, New York 10032, United States; Recruiting
Helen B Simpson, MD, Email: hbs1@columbia.edu

Richard H. Weisler, MD, PA, and Associates, Raleigh, North Carolina 27609, United States; Recruiting
Richard Weisler, MD, Email: rweisler@aol.com

Quest Therapeutics of Avon Lake, Avon Lake, Ohio 44012, United States; Recruiting
Diab Almhana, MD, Email: drbf4646@hotmail.com

Lindner Center of HOPE University of Cincinnati, Mason, Ohio 45040, United States; Recruiting
Susan McElroy, MD, Email: susan.mcelroy@lindnercenter.org

Center for Treatment and Study of Anxiety University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States; Recruiting
Edna Foa, PhD, Email: foa@mail.med.upenn.edu

The Body Dysmorphic Disorder (BDD) Program, Providence, Rhode Island 02903, United States; Recruiting
Katharine Phillips, MD, Email: kphillips4@lifespan.org

Community Clinical Research, Inc, Austin, Texas 78754, United States; Recruiting
David Brown, MD, Email: david.brown@communityclinical.com

Clinical Trials of Texas, Inc, San Antonio, Texas 78229, United States; Recruiting
Tracy L Schillerstrom, MD, Email: ctt@cttexas.com

Dean Foundation, Middleton, Wisconsin 53562, United States; Recruiting
Leslie Taylor, MD, Email: leslie.taylor@deancare.com

The Rogers Center for Research and Training, Milwaukee, Wisconsin 53227, United States; Recruiting
John Greist, MD, Email: jgreist@healthtechsys.com

Additional Information

Starting date: January 2011
Last updated: October 27, 2011

Page last updated: December 08, 2011

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