Melatonin Agonist Effects of Tasimelteon Versus Placebo in Patients With Major Depressive Disorder (MAGELLAN)

• Compare the safety and tolerability of tasimelteon to placebo [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
  • To assess the number of participants with changes in clinical laboratory and ECG data.
  • Recording of adverse events and vital signs.
• Compare the efficacy of tasimelteon to placebo on circadian rhythms and sleep parameters [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
• Compare the impact of treatment with tasimelteon to placebo on sexual functioning and quality of life [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
  -As measured by the Arizona Sexual Experience Scale (ASEX) and Sheehan Disability Scale (SDS).
• Assess suicidality in subjects taking tasimelteon or placebo [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
  -Measured using the Columbia-Suicide Severity Rating Scale (C-SSRS).
• Explore the contribution of genetic factors on efficacy and safety outcomes [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
• To evaluate the efficacy of tasimelteon compared to placebo using MADRS, CGI-S and HAM-A [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]

The purpose of this study is to evaluate the safety and efficacy of an 8-week double-masked treatment of tasimelteon or placebo in male and female subjects with Major Depressive Disorder.

This is a randomized, parallel, double-masked, placebo-controlled, multicenter outpatient study comparing tasimelteon with placebo in the treatment of subjects with Major Depressive Disorder (MDD).

The study has three phases: the pre-randomization phase, the randomization phase, and an open-label extension phase. The pre-randomization phase comprises a screening visit where subject's initial eligibility will be evaluated. The randomization phase is comprised of an 8-week double-masked segment. Subjects meeting all entry criteria for the study will enter the randomization phase. During this phase, subjects will be asked to take either 20 mg tasimelteon or placebo for 8 weeks in a double-masked fashion. At the end of the 8-week double-masked phase, those subjects who completed the 8-week treatment phase will be offered to enroll into a 52-week open-label extension where each subject will receive daily doses of 20 mg tasimelteon.

• Drug: tasimelteon
  20 mg once daily
• Drug: placebo
  once daily

• Experimental: tasimelteon
  Intervention: Drug: tasimelteon
• Placebo Comparator: placebo
  Intervention: Drug: placebo

Inclusion Criteria:

• Subjects with diagnosis of MDD, single or recurrent episode, according to DSM-IV TR criteria;
• Current episode ≥4 weeks and ≤1 year;
• CGI-Severity score ≥4 at screening and baseline.

Exclusion Criteria:

• Lifetime history of bipolar disorder (I or II), schizophrenia, schizoaffective disorder, eating disorder, or obsessive-compulsive disorder;
• Any other current Axis I (except general anxiety disorder as long as it is not considered the primary disorder) or Axis II disorder;
• A positive test for drugs of abuse at the screening visit and/or history of drug or alcohol abuse/dependence as defined in DSM-IV TR, Diagnostic Criteria for Drug and Alcohol Abuse and Dependence, within the past 12 months;
• Formal psychotherapy within 3 months of the screening visit. General supportive psychotherapy is acceptable;
• Participation in a previous tasimelteon trial. Other protocol-defined inclusion/exclusion criteria may apply