Melatonin Agonist Effects of Tasimelteon Versus Placebo in Patients 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.

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