A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Once a Day, TAK-375 (Ramelteon) Tablet for Sublingual Administration (TAK-375SL Tablet) in the Treatment of Acute Depressive Episodes Associated With Bipolar I Disorder in Adult Patients Who Are on Lithium and/or Valproate
Overview
- Phase
- Phase 3
- Intervention
- Ramelteon SL
- Conditions
- Acute Depressive Episode
- Sponsor
- Takeda
- Enrollment
- 490
- Primary Endpoint
- Change From Baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at Week 6
- Status
- Terminated
- Last Updated
- 9 years ago
Overview
Brief Summary
The purpose of this study is to determine the efficacy and safety of Ramelteon, once daily (QD), sublingual (SL), in adult participants with acute depressive episodes associated with Bipolar I disorder.
Detailed Description
Ramelteon sublingual formulation is being developed by Takeda Pharmaceutical Company Limited for maintenance therapy of Bipolar I disorder. Participants will be seen twice during the first week of treatment, weekly during the first 2 weeks of treatment and then every 2 weeks up to the end of the 8-week treatment period. Participants who complete the 8-week treatment period will have a follow-up visit approximately seven days after the last visit. A safety follow-up phone call will be made 30 days after completion of the 8-week treatment period. Based on the recommendation of the Independent Data Monitoring Committee which determined that the study data had met pre-determined criteria for futility, Takeda has made a decision to terminate the study. No safety concerns were identified by the Independent Data Monitoring Committee
Investigators
Eligibility Criteria
Inclusion Criteria
- •In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.
- •The participant or, when applicable, the participant's legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.
- •The participant is a man or woman aged between 18 and 75 years, inclusive.
- •The participant suffers from Bipolar I Disorder, Most Recent Episode Depressed as the primary diagnosis according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria (classification code 296.5x) and confirmed by the Structured Clinical Interview for DSM Disorders (SCID).
- •The reported duration of the current Major Depressive Episode (MDE) is at least four weeks and less than 6 months.
- •The participant has a Young Mania Rating Scale (YMRS) score of ≤10 both at the Screening and Baseline visits.
- •The participant has a Montgomery-Åsberg Depression Rating Scale (MADRS) total score ≥24 at the Screening and Baseline Visits.
- •The participant has a Clinical Global Impression Scale - Severity (CGI-S) score of ≥4 at the Screening and Baseline Visits.
- •Hamilton Rating Scale for Anxiety (HAM-A) score is ≤21 at Screening and Baseline visits.
- •The participant has a lithium and/or valproate levels within therapeutic range (0.6 - 1.2 mEq/L for lithium or 50-125 mcg/ml for valproate) at screening. If the patient does not have a lithium and/or valproate level within therapeutic range at screening, they must have a lithium and/or valproate levels within the therapeutic range between Day - 15 to Day -30 of screening.
Exclusion Criteria
- •The participant has received any investigational compound \<30 days before Screening or 5 half-lives prior to Screening.
- •The participant has received ramelteon in a previous clinical study or has ever used ramelteon.
- •The participant is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in conduct of this study (e.g., spouse, parent, child, sibling) or may consent under duress.
- •The participant has one or more of the following:
- •Any current psychiatric disorder other than Bipolar I Disorder, Most Recent Episode Depressed as defined in the DSM-IV-TR, as assessed by the SCID.
- •Current or history of: schizophrenia, unipolar depression with psychotic features, bipolar depression with psychotic features, any other psychotic disorder (with the exception of psychosis associated with a manic episode), mental retardation, organic mental disorders, or mental disorders due to a general medical condition as defined in the DSM-IV-TR.
- •Current diagnosis or history of alcohol or other substance abuse or dependence (excluding nicotine or caffeine) as defined in the DSM-IV-TR that has not been in full and sustained remission for at least one year from the day of screening. (Participant must also have negative urine drug screen prior to Baseline).
- •Presence or history of a clinically significant neurological disorder (including epilepsy).
- •Neurodegenerative disorder (Alzheimer disease, Parkinson disease, multiple sclerosis, Huntington disease, etc).
- •Any Axis II disorder that might compromise the study.
Arms & Interventions
Ramelteon SL 0.1 mg
Ramelteon SL 0.1 mg, tablets, sublingual (SL) \[dissolved under the tongue\], once daily (QD), every night at bedtime for up to 8 weeks.
Intervention: Ramelteon SL
Ramelteon SL 0.4 mg
Ramelteon SL 0.4 mg, tablets, sublingual, once daily, every night at bedtime for up to 8 weeks.
Intervention: Ramelteon SL
Ramelteon SL 0.8 mg
Ramelteon SL 0.8 mg tablets, sublingual, once daily, every night at bedtime for up to 8 weeks.
Intervention: Ramelteon SL
Placebo
Ramelteon SL placebo-matching, tablets, sublingual, once daily, every night at bedtime for up to 8 weeks.
Intervention: Placebo
Outcomes
Primary Outcomes
Change From Baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at Week 6
Time Frame: Baseline and Week 6
The change between MADRS score at week 6 relative to Baseline. MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (i.e., apparent sadness, reported sadness, inner tension, etc.) rated on a 7-point Likert scale from 0 (normal) to 6 (most abnormal) with a total score range from 0 to 60. Higher scores indicate greater severity of symptoms. A negative change from Baseline indicates improvement. A mixed measures repeated measures (MMRM) model was used for analysis with baseline\*week, pooled center, week, treatment, baseline, and week\*treatment as factors in the analysis.
Secondary Outcomes
- Change From Baseline in Sheehan Disability Scale (SDS) Total Score at Week 6(Baseline and Week 6)
- Change From Baseline in Clinical Global Impression Scale-Severity (CGI-S) at Week 6(Baseline and Week 6)
- Change From Baseline in the Quick Inventory of Depressive Symptomatology - Self-Rated16 (QIDS-SR16) Total Score at Week 6(Baseline and Week 6)
- Change From Baseline in Quality of Life, Enjoyment and Satisfaction Questionnaire (Q-LES-Q-SF) Short Form Total Score at Week 6(Baseline and Week 6)
- Percentage of Participants With MADRS Remission at Week 6, With Remission Defined as a MADRS Total Score ≤10(Week 6)
- Percentage of Participants With MADRS Response at Week 6, With Response Defined as a ≥ 50% Decrease in the MADRS Total Score From Baseline(Baseline and Week 6)
- Change From Baseline in Young Mania Rating Scale (YMRS) Total Score at Week 6(Baseline and Week 6)
- Clinical Global Impression Scale-Improvement (CGI-I) Score at Week 6(6 Weeks)