A Safety and Efficacy Study of Ramelteon Tablets for Sublingual Administration (TAK-375SL) in the Maintenance Treatment of Bipolar 1 Disorder

NCT01685151 | Withdrawn Phase 3

• 3 other identifiers: TAK-375SL_3022012-001373-85U1111-1129-5093
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

To evaluate the efficacy and safety of once a day ramelteon tablets for sublingual administration (TAK-375SL) in the maintenance treatment of bipolar 1 disorder.

Conditions

Bipolar Disorder

Keywords

Drug therapy

Outcome Measures

Primary Outcomes (1)

• The time from randomization to relapse due to Bipolar 1 Disorder as Determined by Composite Criteria.

  The time from randomization to relapse as determined by any of the following criteria during the 12-month double-blind treatment period: * PI judgment * Depression (Montgomery-Asberg Depression Rating Scale \[MADRS\] ≥16); * Mania/hypomania (Young Mania Rating Scale \[YMRS\] ≥16); * Mixed episode (MADRS ≥16 and YMRS ≥16); * Psychiatry hospitalization for bipolar disorder; * Electroconvulsive therapy or any psychotropic medication change prescribed for the treatment of depression, mania/hypomania or mixed episodes.

  12 months

Secondary Outcomes (10)

• The time from randomization to relapse due to depression as Determined by Composite Criteria.

  12 months

• The Time from randomization to relapse due to mania/hypomania or mixed episode as Determined by Composite Criteria.

  12 Months

• The time from randomization to relapse in depression

  12 Months

• The time from randomization to relapse in mania/hypomania

  12 months

• The time from randomization to relapse in mixed episode

  12 months

Study Arms (3)

Ramelteon SL (Dose 1)

EXPERIMENTAL

Ramelteon SL tablets, sublingual, once daily, at night time for up to 12 months.

Drug: Ramelteon SL (Dose 1)

Ramelteon SL (Dose 2)

EXPERIMENTAL

Ramelteon SL tablets, sublingual, once daily, at nigh time for up to 12 months

Drug: Ramelteon SL (Dose 2)

Placebo

PLACEBO COMPARATOR

Ramelteon SL placebo-matching tablets, sublingual, once daily, at night time for up to 12 months.

Drug: Placebo

Interventions

Ramelteon SL (Dose 1) DRUG

Ramelteon tablets for sublingual administration

Also known as: TAK-375SL, Rozerem

Ramelteon SL (Dose 1)

Ramelteon SL (Dose 2) DRUG

Ramelteon tablets for sublingual administration

Also known as: TAK-375SL, Rozerem

Ramelteon SL (Dose 2)

Placebo DRUG

Placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• In the opinion of the investigator, the subject is capable of understanding and complying with protocol requirements.
• The subject or a 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 subject suffers from bipolar 1 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 subject is a man or woman aged between 18 and 75 years, inclusive.
• The subject has an identified caregiver or person responsible (eg. 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, hypomania) is between 8 weeks and 9 months prior to screening.
• The subject has been stable in the opinion of the PI for at least 8 weeks prior to baseline from their most recent mood episode.
• The subject has a MADRS total score ≤12 at the Screening and Baseline visits.
• The subject has a YMRS score of ≤10 both at the Screening and Baseline visits.
• The subject has a CGI-S score of ≤2 at the Screening and Baseline visits.
• HAM-A score is ≤21 at Screening and Baseline visits.
• The subject's medications for bipolar 1 disorder are stable ie, no change in psychotropic medications and no dose adjustment of psychotropic medications for bipolar 1 disorder has been made for at least 8 weeks prior to the randomization.
• A male subject who is nonsterilized and sexually active with a female partner of childbearing potential agrees to use adequate contraception from signing of informed consent throughout the duration of the study and for 30 days after the last dose.
• A female subject of childbearing potential who is sexually active with a nonsterilized male partner agrees to use routinely adequate contraception from signing of informed consent throughout the duration of the study and for 30 days after the last dose.

You may not qualify if:

• The subject has received any investigational compound \<30 days before Screening or 5 half-lives prior to Screening, whichever is longer.
• The subject has ever received TAK-375 or TAK-375 SL in a previous clinical study or has ever used ramelteon.
• The subject 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 subject has one or more of the following:
• Any current psychiatric disorder which is the primary focus of treatment other than bipolar 1 disorder as defined in the DSM-IV-TR, as assessed by the SCID.
• Current or history of: schizophrenia or any other psychotic disorder, including schizoaffective disorder, major depression with psychotic features, bipolar depression with psychotic features (with the exception of psychosis associated with a manic or mixed episode), 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 least three months from the day of screening (Subject must also have negative urine drug screen at Screening and Baseline; only exception is for benzodiazepines and opiates provided the subject 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 least three months from the day of screening.(Subject must also have negative urine drug screen at Screening and Baseline; only exception is for benzodiazepines and opiates provided the subject 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).
• Any Axis II disorder that might compromise the study.
• History of Rapid Cycling Bipolar Disorder: Subjects who have more than 8 episodes of mood disorder per year. The episodes must meet both the duration and symptom criteria for a Major Depressive, Manic, Mixed, or Hypomanic episode and must be demarcated by either a period of full remission or by a switch to an episode of the opposite polarity. Manic, Hypomanic, and Mixed Episodes are counted as being on the same pole. Each mood episode must be confirmed by appropriate patient history or formal diagnosis by medical practitioner.
• The subject experienced the first episode of mood disorder after the age of 55 years.
• The subject is on any other medications other than antidepressants (except fluvoxamine), mood stabilizers (lithium, valproate, lamotrigine), or atypical antipsychotics (risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole,) for bipolar 1 disorder. If the subject is on lithium and/or valproate, the levels should be in the specified range: lithium (serum levels up to 1.2 mEq/L); valproate (serum levels up to 125 mcg/ml) at screening. If the subject is on any other psychotropic medications, at the investigators discretion, withdrawal of these medications is allowed two weeks prior to the baseline visit.
• The subject is on no medications or taking only antidepressant medications (or taking only other medications not commonly used as standard treatment for bipolar I disorder, such as benzodiazepines).

Sponsors & Collaborators

• Takeda: lead

Related Links

• Rozerem Package Insert

MeSH Terms

Conditions

Bipolar Disorder

Interventions

ramelteon

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders

Study Officials

• Medical Director Clinical Science

  Takeda Global Research and Development Center, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 31, 2012
• First Posted: September 14, 2012
• Study Start: September 1, 2012
• Primary Completion: November 1, 2015
• Study Completion: November 1, 2015
• Last Updated: January 23, 2013

Record last verified: 2013-01