Safety and Efficacy Study of Ramelteon (TAK-375) Tablets for Sublingual Administration (SL) in Adults With Bipolar 1 Disorder

NCT01677182 | Terminated Phase 3 Results DMC

• 4 other identifiers: TAK-375SL_3012012-001357-10U1111-1129-518412/EM/0391
• Study Type: interventional
• Target: 535
• Locations: 10 countries
• Sites: 104

Brief Summary

To evaluate the efficacy of ramelteon for treatment of acute depressive episodes associated with Bipolar 1 Disorder.

Conditions

Bipolar Disorder

Keywords

Drug therapy

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Week 6

  The MADRS is a clinician rated, validated and widely used scale to measure overall severity of depressive symptoms. It consists of 10-item rated from 0(normal) to 6(most abnormal) with a total score range from 0 to 60. Higher scores indicate greater severity of symptoms.

  Baseline and Week 6

Secondary Outcomes (8)

• 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

  Week 6

• Change From Baseline in Clinical Global Impression Scale-Severity (CGI-S) to 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 Sheehan Disability Scale (SDS) Total Score at Week 6

  Baseline and Week 6

Study Arms (3)

Ramelteon SL (Dose 1)

EXPERIMENTAL

Ramelteon SL tablets, sublingual, once daily, at night time for up to 6 weeks.

Drug: Ramelteon

Ramelteon (Dose 2)

EXPERIMENTAL

Ramelteon SL tablets, sublingual, once daily, at night time for up to 6 weeks.

Drug: Ramelteon

Placebo

PLACEBO COMPARATOR

Ramelteon SL placebo-matching tablets, sublingual, once daily, at night time for up to 6 weeks.

Drug: Placebo

Interventions

Ramelteon DRUG

Ramelteon tablets for sublingual administration

Also known as: TAK-375SL, Rozerem

Ramelteon (Dose 2); Ramelteon SL (Dose 1)

Placebo DRUG

Ramelteon placebo-matching tablets for sublingual administration

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, when applicable, the subject'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 subject suffers from Bipolar 1 Disorder, Most Recent Episode Depressed as the primary diagnosis according to DSM-IV-TR criteria (classification code 296.5x) and confirmed by the SCID.
• The subject is a man or woman aged between 18 and 75 years, inclusive.
• The reported duration of the current Major Depressive Episode (MDE) is at least four weeks and less than 6 months.
• The subject has a YMRS total score of ≤10 both at the Screening and Baseline Visits.
• The subject has a MADRS total score of ≥24 at the Screening and Baseline Visits.
• The subject has a CGI-S score of ≥4 at the Screening and Baseline Visits.
• The subject has HAM- A total score of ≤21 at Screening and Baseline Visits.
• The subject is on lithium and/or one other mood stabilizer (lamotrigine or valproic acid) and/or one atypical antipsychotic (risperidone or olanzapine or aripiprazole or ziprasidone). Patients may be on one, two, or three medications but no more than one from each group.
• If the subject is on lithium and/or valproic acid, the trough serum levels must be less than 1.2 mEq/L for lithium and the trough serum must be less than 125 mcg/ml for valproic acid. Downward dose adjustment is allowed to lower trough serum levels for lithium and/or valproic acid below the maximum allowed. This must be confirmed at least two weeks prior to baseline.
• The subject screened must have \<25% improvement in MADRS total score from screening to baseline visit with a minimum of two weeks between screening and baseline visits.
• 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 of the study drug.
• A male subject who is nonsterilized and sexually active with 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 of study drug.

You may not qualify if:

• The subject has received any investigational compound \<30 days before Screening or 5 half-lives whichever is longer prior to Screening.
• The subject has received TAK-375 or TAK-375SL in a previous clinical study or has ever used ramelteon.
• The subject is an immediate family member, study site employee, or is in a dependant 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, Most Recent Episode Depressed as defined in the DSM-IV-TR, as assessed by the SCID.
• Current or history of: schizophrenia, schizoaffective disorder, unipolar depression with psychotic features, bipolar depression with psychotic features, any other psychotic disorder (with the exception of psychosis associated with a manic or mixed episode), mental retardation, organic mental disorders, OCD, 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). Note that a positive drug screen for opiates and benzodiazepines is allowed 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). Note that a positive drug screen for opiates and benzodiazepines is allowed provided the subject has a valid prescription.
• 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.
• History of Rapid Cycling Bipolar Disorder: Patients 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 current depressive symptoms of the subject are considered by the investigator to have been resistant to 2 adequate treatment trials with any of the mood stabilizers (specifically started to treat the current depressive episode) and/or medications approved for acute bipolar depression (e.g. quetiapine, olanzapine + fluoxetine \[US only\]) for at least 6 weeks duration each.
• The subject is on any psychotropic medications other than the protocol allowed medications for at least 2 weeks prior to the Baseline visit. If a subject is taking any protocol excluded medications (e.g. antidepressants, typical antipsychotics) or is taking more than one of the allowed mood stabilizer and/or atypical antipsychotic medications, and if the patient is considered appropriate by the PI, these medications must be washed out for at least 2 weeks prior to the Baseline visit.

Sponsors & Collaborators

• Takeda: lead

Study Sites (104)

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Birmingham, Alabama, United States

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Anaheim, California, United States

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Glendale, California, United States

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Imperial, California, United States

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Los Angeles, California, United States

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Oakland, California, United States

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Oceanside, California, United States

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Pico Rivera, California, United States

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San Diego, California, United States

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Stanford, California, United States

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Hartford, Connecticut, United States

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Coral Springs, Florida, United States

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Deerfield Beach, Florida, United States

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Gainesville, Florida, United States

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Jacksonville, Florida, United States

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Maitland, Florida, United States

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Oakland Park, Florida, United States

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Orlando, Florida, United States

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Tampa, Florida, United States

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West Palm Beach, Florida, United States

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Chicago, Illinois, United States

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Joliet, Illinois, United States

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Naperville, Illinois, United States

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Oak Brook, Illinois, United States

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Lafayette, Indiana, United States

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Boston, Massachusetts, United States

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St Louis, Missouri, United States

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Buffalo, New York, United States

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New York, New York, United States

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Staten Island, New York, United States

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The Bronx, New York, United States

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Avon Lake, Ohio, United States

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Cincinnati, Ohio, United States

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Garfield Heights, Ohio, United States

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Mason, Ohio, United States

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Oklahoma City, Oklahoma, United States

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Memphis, Tennessee, United States

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San Antonio, Texas, United States

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Bothell, Washington, United States

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Spokane, Washington, United States

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Waukesha, Wisconsin, United States

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Burgas, Bulgaria

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Kazanlak, Bulgaria

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Lovech, Bulgaria

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Novi Iskar, Bulgaria

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Pleven, Bulgaria

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Plovdiv, Bulgaria

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Rousse, Bulgaria

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Sofia, Bulgaria

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Tzerova Koria, Bulgaria

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Varna, Bulgaria

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Brno, Czechia

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Litoměřice, Czechia

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Olomouc, Czechia

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Pilsen, Czechia

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Prague, Czechia

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Bochum, North Rhine-Westphalia, Germany

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Berlin, State of Berlin, Germany

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Berlin, Germany

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Westerstede, Germany

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Bialystok, Poland

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Choroszcz, Poland

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Oradea, Bihor County, Romania

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Cluj-Napoca, Cluj, Romania

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Craiova, Dolj, Romania

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Târgovişte, Dâmbovița County, Romania

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Bucharest, Romania, Romania

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Arad, Romania

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Bucharest, Romania

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Cluj-Napoca, Romania

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Craiova, Romania

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Iași, Romania

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Târgovişte, Romania

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Talagi, Arkhangelskaya oblast, Russia

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Orenburg, Orenburg Oblast, Russia

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Staritsa Settlement, Orenburg Oblast, Russia

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Saint Petersburg, Sankt-Peterburg, Russia

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Town. Tonnelniy, Stavropol Region, Russia

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Arkhangelsk, Russia

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Moscow, Russia

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Nizhny Novgorod, Russia

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Saint Petersburg, Russia

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Smolensk, Russia

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Stavropol, Russia

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Belgrade, Serbia, Serbia

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Kragujevac, Sumadija, Serbia

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Novi Sad, Vojvodina, Serbia

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Belgrade, Serbia

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Kragujevac, Serbia

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Niš, Serbia

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Novi Kneževac, Serbia

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Simferopol, Autonomous Republic of Crimea, Ukraine

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Oleksandrivka, Kominternivske District, Odesa Oblast, Ukraine

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Simferopol, The Autonomous Republic of Crimea, Ukraine

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Vinnytsia, Vinnytsia Oblast, Ukraine

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Kharkiv, Ukraine

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Luhansk, Ukraine

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Odesa, Ukraine

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Poltava, Ukraine

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Ternopil, Ukraine

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Oxford, Oxfordshire, United Kingdom

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Birmingham, United Kingdom

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London, United Kingdom

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Newcastle upon Tyne, United Kingdom

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Related Links

• Rozerem Package Insert

MeSH Terms

Conditions

Bipolar Disorder

Interventions

ramelteon

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders

Results Point of Contact

• Title: Medical Director
• Organization: Takeda

clinicaltrialregistry@tpna.com

+1-877-825-3327

Study Officials

• Medical Director Clinical Science

  Takeda Global Research and Development Center, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

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 29, 2012
• First Posted: August 31, 2012
• Study Start: August 1, 2012
• Primary Completion: August 1, 2014
• Study Completion: September 1, 2014
• Last Updated: March 16, 2016
• Results First Posted: March 16, 2016

Record last verified: 2016-02

Locations

UA (9); DE (4); BU (10); US (41); RU (11); PL (2); CZ (5); GB (4); RO (11); SE (7)