Clinical trial NCT00775203: A Randomized, Double-blind, Two-arm Study Comparing the Efficacy and Safety of Trazodone Contramid® OAD and Placebo in the Treatment of Unipolar Major Depressive Disorder.
Official title: A Randomized, Double-blind, Two-arm Study Comparing the Efficacy and Safety of Trazodone Contramid® OAD and Placebo in the Treatment of Unipolar Major Depressive Disorder.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Major Depressive Disorder
Keywords: Unipolar
Lead sponsor: Labopharm Inc.
Sponsor class: INDUSTRY
First posted: 2008-10-20
Enrollment: 412
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study was to demonstrate efficacy, safety and clinical benefit of Trazodone Contramid® OAD (Once A Day) in the treatment of Unipolar Major Depressive Disorder (MDD).

Detailed description: This two-arm, multicentre, randomized, placebo-controlled, double-blind, parallel-design study consisted of a baseline phase (screening and wash-out) and a double-blind randomized phase (randomization to Trazodone Contramid® OAD or placebo). The total study duration including wash-out of prohibited medications was approximately 11 weeks; the total duration of the randomized phase was 8 weeks (titration: 2 weeks + treatment: 6 weeks).

Eligibility criteria: Inclusion Criteria:

* Males or females.
* Aged 18 years or older.
* Fulfills Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria for Unipolar Major Depressive Disorder (MDD) (Axis I) as confirmed by the Mini-International Neuropsychiatric Interview (MINI).
* The primary DSM-IV Axis I diagnosis should be MDD (296.22, 296.23, 296.32, 296.33); any subject meeting criteria for another, non excluded Axis I disorder, must demonstrate MDD as the primary disorder.
* The current episode of MDD should have lasted for a minimum of 1 month, whether the patient has been diagnosed with one single or recurrent episodes.
* Presence of dysphoria for most days over the past four weeks.
* Montgomery-Åsberg Depression Rating Scale (MADRS) total score of at least 26 at screening and baseline.
* Oral and written language comprehension at a level sufficient to comply with the protocol and to complete study-related materials.
* Sign and date a written Informed Consent Form (ICF) approved by a Research Ethic Board (REB) which has also been signed and dated by the Investigator prior to study participation.

Exclusion Criteria:

* DSM-IV Major Depressive Disorder Specifiers: \[a\] With Catatonic Features; \[b\] With Postpartum Onset; \[c\] With Seasonal Pattern;
* Presence of any of the following DSM-IV Axis I disorders: generalized anxiety disorder, panic disorder, social phobia, obsessive-compulsive disorder, post-traumatic stress disorder, eating disorder, bipolar disorder, alcohol/substance abuse or dependence (caffeine and nicotine allowed), any psychotic disorder.
* Depression secondary to stroke, cancer or other severe medical illnesses.
* Positive urine drug screen at screening visit.
* History or present condition of any DSM-IV Axis II disorder.
* History of treatment refractory major depressive episodes defined as incomplete or no therapeutic response to two prior courses of at least one month of conventional antidepressant drug treatment in adequate dosages.
* Currently in psychotherapy (at least one session in the past month with a plan for continuing) with a licensed/registered/certified mental health provider, marriage counselor, or family therapist.
* Meet criteria for high suicide risk on the MINI suicide scale, or in the opinion of the investigator is inappropriate for the trial due to clinically significant suicidal or homicidal potential.
* Require hospitalization for treatment of the current episode of depression.
* Uncorrected hypo- or hyperthyroidism.
* A history of seizures other than pediatric febrile seizure.
* A history of cardiac arrythmias requiring therapy.
* A history of myocardial infarction within 1 year before screening.
* Clinically significant abnormal findings of Electrocardiography (ECG), laboratory parameters.
* Unwilling to discontinue use of any antidepressants, including herbal remedies, for a minimum of 5 drug half-lives prior to screening.
* Unwilling to discontinue use of prohibited medications for a minimum of 5 drug half-lives prior to screening.
* Treatment within the last 3 weeks with Monoamine Oxidase (MAO) inhibitors.
* Use of the following concomitant treatment during the study:

  * medications causing QT prolongation (e.g. amiodarone, droperidol, erythromycin).
  * medications causing PR prolongation (e.g. digoxin).
  * Anti -psychotics (e.g. haloperidol).
  * protease inhibitors such as ritonavir and indinavir.
* Hormonal treatment (e.g. estrogen, oral contraceptives) which has started within 3 months of study entry.
* Treatment with another investigational agent within the last 30 days.
* Known and documented allergy to trazodone or any structurally similar drugs.
* Previous failure of treatment with trazodone, or previous discontinuation of treatment with trazodone due to Adverse Events.
* Bowel disease causing malabsorption.
* Serious, unstable illnesses during the 3 months before screening including but not limited to: hepatic, renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic or hematological disease.
* Pregnant or lactating, or is of childbearing potential and not willing to use an approved method of contraception.
* Significant liver disease, defined as active hepatitis or elevated liver enzymes \>3 times the upper boundary of the normal range.
* Significant renal disease, defined as Blood Urea Nitrogen (BUN) and/or creatinine \>3 times the upper boundary of the normal range clearance.
* Any other condition that, in the opinion of the investigators, would adversely affect the patient's ability to complete the study or its measures.

Primary outcomes:
measure: Change in Hamilton Depression Scale (HAMD-17) Total Score From Baseline
timeFrame: Baseline to Week 8
Secondary outcomes:
measure: HAMD-17 Responders at Each Visit
timeFrame: Weeks 1, 2, 3, 4, 6, 8
measure: HAMD-17 Remitters at Each Visit
timeFrame: Weeks 1, 2, 3, 4, 6, 8
measure: Change in HAMD-17 Depressed Mood Item (Item 1) Score From Baseline to Each Visit
timeFrame: Baseline to Weeks 1, 2, 3, 4, 6, 8
measure: Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score From Baseline
timeFrame: Baseline to Week 8
measure: Change From Baseline in Clinical Global Impression of Severity (CGI-S) to Each Visit
timeFrame: Baseline to Weeks 1, 2, 3, 4, 6, 8
measure: Clinical Global Impression - Improvement of Illness (CGI-I) Score at Last Study Visit
timeFrame: Week 8
measure: Patient Global Impression - Improvement of Illness (PGI-I) Score at Last Study Visit
timeFrame: Week 8
measure: Clinical Global Impression - Improvement of Illness (CGI-I) Responders at Last Study Visit
timeFrame: Week 8
measure: Patient Global Impression - Improvement of Illness (PGI-I) Responders at Last Study Visit
timeFrame: Week 8
measure: Overall Quality of Sleep at Each Visit
timeFrame: Weeks 1, 2, 3, 4, 6, 8
measure: Trouble Falling Asleep at Each Visit
timeFrame: Weeks 1, 2, 3, 4, 6, 8
measure: Awakening During the Night at Each Visit
timeFrame: Weeks 1, 2, 3, 4, 6, 8
measure: Discontinuation Due to Lack of Efficacy
timeFrame: Baseline to Week 8
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Mesa
country: United States
state: Arizona
city: Beverly Hills
country: United States
state: California
city: Burbank
country: United States
state: California
city: San Diego
country: United States
state: California
city: Denver
country: United States
state: Colorado
city: Gainesville
country: United States
state: Florida
city: Hialeah
country: United States
state: Florida
city: Jacksonville
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Marietta
country: United States
state: Georgia
city: Smyrna
country: United States
state: Georgia
city: Libertyville
country: United States
state: Illinois
city: Indianapolis
country: United States
state: Indiana
city: Overland Park
country: United States
state: Kansas
city: Clementon
country: United States
state: New Jersey
city: Brooklyn
country: United States
state: New York
city: New York
country: United States
state: New York
city: New-York
country: United States
state: New York
city: Beachwood
country: United States
state: Ohio
city: Cincinnati
country: United States
state: Ohio
city: Dayton
country: United States
state: Ohio
city: Oklahoma City
country: United States
state: Oklahoma
city: Philadelphia
country: United States
state: Pennsylvania
city: Bellaire
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Woodstock
country: United States
state: Vermont
city: Kelowna
country: Canada
state: British Columbia
city: Penticton
country: Canada
state: British Columbia
city: Mount Pearl
country: Canada
state: Newfoundland and Labrador
city: Hamilton
country: Canada
state: Ontario
city: Oakville
country: Canada
state: Ontario
city: Gatineau
country: Canada
state: Quebec
city: Saint-Leonard
country: Canada
state: Quebec
city: Sherbrooke
country: Canada
state: Quebec
Study officials:
References:
citation: Sheehan DV, Croft HA, Gossen ER, Levitt RJ, Brulle C, Bouchard S, Rozova A. Extended-release Trazodone in Major Depressive Disorder: A Randomized, Double-blind, Placebo-controlled Study. Psychiatry (Edgmont). 2009 May;6(5):20-33.