A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Once a Day, TAK-375SL as an Adjunctive Therapy to Treatment-as-Usual in the Maintenance Treatment of Bipolar I Disorder in Adult Patients
Overview
- Phase
- Phase 3
- Intervention
- Ramelteon SL
- Conditions
- Bipolar Disorder
- Sponsor
- Takeda
- Enrollment
- 642
- Primary Endpoint
- Time From Randomization to Any Relapse
- 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 nightly before bedtime (QHS), sublingual (SL), in the maintenance treatment of Bipolar I Disorder in adult patients.
Detailed Description
TAK-375SL (ramelteon sublingual formulation) is being developed by Takeda Pharmaceutical Company Limited as an adjunctive treatment in the maintenance therapy of bipolar I disorder. Participants will be seen twice a month for the first two months and then once every month up to the end of the 9-month treatment period. Participants who complete the 9-month treatment period will have a follow-up visit approximately seven days after the last visit. A safety followup phone call will be made 30 days after completion of the 9-month 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 suffers from bipolar I disorder, according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria and is confirmed by the Structured Clinical Interview for DSM Disorders (SCID).
- •The participant is a man or woman aged between 18 and 75 years, inclusive.
- •The participant has an identified caregiver or person responsible (e.g. family member, spouse, case worker or nurse at a residential living (facility) that is considered reliable by the investigator.
- •The most recent mood episode (depression, mania, mixed episode) is within the past 9 months from screening.
- •The participant has been in remission in the opinion of the principal investigator (PI) for at least 8 weeks prior to baseline from their most recent mood episode.
- •The participant has a Montgomery-Åsberg Depression Rating Scale (MADRS) total score ≤12 at the Screening and Baseline visits.
- •The participant has a Young Mania Rating Scale (YMRS) score of ≤10 both at the Screening and Baseline visits.
- •The participant has a Clinical Global Impression Scale - Severity (CGI-S) score of ≤2 at the Screening and Baseline visits.
Exclusion Criteria
- •The participant has received any investigational compound \<30 days before Screening or 5 half-lives prior to Screening.
- •The participant has ever 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 (eg, spouse, parent, child, sibling) or may consent under duress.
- •The participant has one or more of the following:
- •Any current psychiatric disorder which is the primary focus of treatment other than bipolar I disorder as defined in the DSM-IV-TR, as assessed by the SCID.
- •Current or history of: schizophrenia or any other psychotic disorder, including major depression with psychotic features, bipolar depression with psychotic features (with the exception of psychosis associated with a manic or mixed episode), obsessive-compulsive disorder (OCD), 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 (excluding nicotine or caffeine) as defined in the DSM-IV-TR that has not been in full and sustained remission for at three months from the day of screening (Participant must also have negative urine drug screen at Screening and Baseline; only exception is for benzodiazepines and opiates provided the participant has a valid prescription).
- •Current diagnosis or history of alcohol or other substance dependence (excluding nicotine or caffeine) as defined in the DSM-IV-TR that has not been in full and sustained remission for at six months from the day of screening.(Participant must also have negative urine drug screen at Screening and Baseline; only exception is for benzodiazepines and opiates provided the participant has a valid prescription).
- •Presence or history of a clinically significant neurological disorder (including epilepsy) as determined by the investigator.
- •Neurodegenerative disorder (Alzheimer disease, Parkinson disease, multiple sclerosis, Huntington disease, etc).
Arms & Interventions
Ramelteon SL 0.1 mg
Ramelteon SL 0.1 mg, tablets, sublingual, once daily, every night at bedtime for up to 9 months.
Intervention: Ramelteon SL
Placebo
Ramelteon SL placebo-matching, tablets, sublingual (SL) \[dissolved under the tongue\], once daily, every night at bedtime for up to 9 months.
Intervention: Placebo
Ramelteon SL 0.4 mg
Ramelteon SL 0.4 mg, tablets, sublingual, once daily, every night at bedtime for up to 9 months.
Intervention: Ramelteon SL
Ramelteon SL 0.8 mg
Ramelteon SL 0.8 mg, tablets, sublingual, once daily, every night at bedtime for up to 9 months.
Intervention: Ramelteon SL
Outcomes
Primary Outcomes
Time From Randomization to Any Relapse
Time Frame: Randomization to Month 12 double-blind treatment period
The time from randomization to relapse over 12 months double-blind treatment period as determined by the Principal Investigator (PI) or defined by any of the following criteria: depression \[Montgomery-Åsberg Depression Rating Scale (MADRS) score ≥16\]; mania/hypomania \[Young Mania Rating Scale (YMRS) total score ≥14\]; mixed episode \[MADRS score ≥16 and YMRS total score ≥16\]; or, whether participant receives psychiatric hospitalization for bipolar disorder, electroconvulsive therapy (ECT) or any psychotropic medication change prescribed for the treatment of depression, mania/hypomania or mixed episodes.
Secondary Outcomes
- Time From Randomization to Relapse Due to Depression(Randomization to Month 12 double-blind treatment period)
- Time From Randomization to Relapse Due to Depression From PI Judgement and/or MADRS ≥16(Randomization to Month 12 double-blind treatment period)
- Time From Randomization to Study Withdrawal for Any Reason(Randomization to Month 12 double-blind treatment period)
- Quality of Life, Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF) Total Score(Baseline and Months 1, 2, 3, 4, 5, 6, 7, 8, 10 and 12)
- Time From Randomization to Relapse Due to Mania/Hypomania(Randomization to 12 Month double-blind treatment period)
- Time From Randomization to Relapse Due to Electroconvulsive Therapy (ECT) Administration(Randomization to Month 12 double-blind treatment period)
- Time From Randomization to Relapse Due to Psychiatric Hospitalization for Bipolar Disorder(Randomization to Month 12 double-blind treatment period)
- Time From Randomization to Relapse Due to Psychotropic Medication Change Prescribed for the Treatment of Depression, Mania/Hypomania or Mixed Episodes(Randomization to Month 12 double-blind treatment period)
- Time From Randomization to Relapse Due to Mania/Hypomania or Mixed Episode(Randomization to Month 12 double-blind treatment period)
- Time From Randomization to Relapse Due to Mixed Episode(Randomization to Month 12 double-blind treatment period)