Major Depressive Disorder
Conditions
Keywords
tasimelteon, Major Depressive Disorder, MDD, depression
Brief summary
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.
Detailed description
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.
Interventions
DRUGtasimelteon
20 mg once daily
DRUGplacebo
once daily
Sponsors
Vanda Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Endpoint at Week 8 Using the Total Score of the Hamilton Depression Rating Scale (HAM-D) | 8 weeks | Hamilton Rating Scale for Depression (HAM-D) assesses the range of symptoms that are most frequently observed in subjects with major depressive disorder (MDD) on a scale from 0 to 52. Higher HAM-D scores indicate more severe levels of depressive symptoms, thus, a negative change from baseline indicates a reduction (or improvement) in depressive symptoms. |
Countries
United States
Participant flow
Pre-assignment details
\*Tasi: subject left country (1); Placebo: sponsor request (1), subject moved (1), IMP schedule (1), subject incarcerated (1), withdrawn after receipt of medical records (1), visit schedule (1) \*\*Tasi: surgery (1), visit schedule (3), +UDS (2), IMP schdule (2), prohibited meds (1), withdrew consent (1), sponsor terminated trial (175)
Participants by arm
| Arm | Count |
|---|---|
| Tasimelteon 20 mg tasimelteon capsules, PO daily for 8 weeks | 254 |
| Placebo Placebo capsules, PO daily for 8 weeks | 253 |
| Open Label Tasimelteon 20 mg capsules, PO daily for 52 weeks | 339 |
| Total | 846 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Double-Masked Phase | Adverse Event | 13 | 4 | 0 |
| Double-Masked Phase | Lack of Efficacy | 2 | 1 | 0 |
| Double-Masked Phase | Lost to Follow-up | 14 | 14 | 0 |
| Double-Masked Phase | Protocol Violation | 9 | 4 | 0 |
| Double-Masked Phase | *Various | 1 | 6 | 0 |
| Double-Masked Phase | Withdrawal by Subject | 18 | 20 | 0 |
| Open Label Extension | Adverse Event | 0 | 0 | 15 |
| Open Label Extension | Lack of Efficacy | 0 | 0 | 24 |
| Open Label Extension | Lost to Follow-up | 0 | 0 | 38 |
| Open Label Extension | Protocol Violation | 0 | 0 | 9 |
| Open Label Extension | **Various | 0 | 0 | 185 |
| Open Label Extension | Withdrawal by Subject | 0 | 0 | 49 |
Baseline characteristics
| Characteristic | Placebo | Open Label Tasimelteon | Total | Tasimelteon |
|---|---|---|---|---|
| Age, Continuous | 42.0 years STANDARD_DEVIATION 12.46 | NA years | 42.9 years STANDARD_DEVIATION 12.54 | NA years |
| Gender Female | 171 participants | 0 participants | 332 participants | 0 participants |
| Gender Male | 0 participants | 117 participants | 175 participants | 0 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 38 / 254 | 53 / 252 | 74 / 339 |
| serious Total, serious adverse events | 2 / 254 | 3 / 252 | 6 / 339 |
Outcome results
Primary
Change From Baseline to Endpoint at Week 8 Using the Total Score of the Hamilton Depression Rating Scale (HAM-D)
Hamilton Rating Scale for Depression (HAM-D) assesses the range of symptoms that are most frequently observed in subjects with major depressive disorder (MDD) on a scale from 0 to 52. Higher HAM-D scores indicate more severe levels of depressive symptoms, thus, a negative change from baseline indicates a reduction (or improvement) in depressive symptoms.
Time frame: 8 weeks
Population: The Intent-to-Treat (ITT) Population included any subject randomized into the study that receives a dose of study medication and that has completed at least one post-baseline efficacy measurement while on study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tasimelteon | Change From Baseline to Endpoint at Week 8 Using the Total Score of the Hamilton Depression Rating Scale (HAM-D) | -8.19 units on a scale | Standard Error 0.45 |
| Placebo | Change From Baseline to Endpoint at Week 8 Using the Total Score of the Hamilton Depression Rating Scale (HAM-D) | -7.83 units on a scale | Standard Error 0.45 |
| Open Label Tasimelteon | Change From Baseline to Endpoint at Week 8 Using the Total Score of the Hamilton Depression Rating Scale (HAM-D) | -13.6 units on a scale | Standard Error 0.34 |