Efficacy and Safety of Ramelteon Sublingual as Adjunctive Therapy for Maintenance Treatment of Bipolar I Disorder
NCT ID: NCT01467713
Last Updated: 2016-05-16
Study Results
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View full resultsBasic Information
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TERMINATED
PHASE3
642 participants
INTERVENTIONAL
2011-12-31
2015-03-31
Brief Summary
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Detailed Description
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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
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
QUADRUPLE
Study Groups
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Placebo
Ramelteon SL placebo-matching, tablets, sublingual (SL) \[dissolved under the tongue\], once daily, every night at bedtime for up to 9 months.
Placebo
Ramelteon sublingual (SL) placebo-matching tablets
Ramelteon SL 0.1 mg
Ramelteon SL 0.1 mg, tablets, sublingual, once daily, every night at bedtime for up to 9 months.
Ramelteon SL
Ramelteon sublingual (SL) tablets
Ramelteon SL 0.4 mg
Ramelteon SL 0.4 mg, tablets, sublingual, once daily, every night at bedtime for up to 9 months.
Ramelteon SL
Ramelteon sublingual (SL) tablets
Ramelteon SL 0.8 mg
Ramelteon SL 0.8 mg, tablets, sublingual, once daily, every night at bedtime for up to 9 months.
Ramelteon SL
Ramelteon sublingual (SL) tablets
Interventions
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Ramelteon SL
Ramelteon sublingual (SL) tablets
Placebo
Ramelteon sublingual (SL) placebo-matching tablets
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
2. 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.
3. 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).
4. The participant is a man or woman aged between 18 and 75 years, inclusive.
5. 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.
6. The most recent mood episode (depression, mania, mixed episode) is within the past 9 months from screening.
7. 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.
8. The participant has a Montgomery-Åsberg Depression Rating Scale (MADRS) total score ≤12 at the Screening and Baseline visits.
9. The participant has a Young Mania Rating Scale (YMRS) score of ≤10 both at the Screening and Baseline visits.
10. The participant has a Clinical Global Impression Scale - Severity (CGI-S) score of ≤2 at the Screening and Baseline visits.
11. Hamilton Rating Scale for Anxiety (HAM-A) score is ≤21 at Screening and Baseline visits.
12. The participant's medications for bipolar I disorder are stable i.e., no dose adjustment has been made for at least 8 weeks prior to the randomization
13. A male participant who is nonsterilized and sexually active with a female partner of childbearing potential agrees to use adequate contraception from signing of informed consent through the duration of the study and for 30 days after the last dose.
14. A female participant of childbearing potential who is sexually active with a non sterilized 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.
Exclusion Criteria
2. The participant has ever received ramelteon in a previous clinical study or has ever used ramelteon.
3. 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.
4. 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).
* 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.
5. The participant experienced the first episode of mood disorder after the age of 65 years.
6. The participant is on any other medications other than antidepressants (except fluvoxamine), mood stabilizers (lithium, valproate, lamotrigine), or atypical antipsychotics (risperidone, 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.
7. The participant has received electroconvulsive therapy, vagal nerve stimulation, or repetitive transcranial magnetic stimulation within 6 months prior to Screening.
8. The participant has started receiving formal cognitive or behavioral therapy, systematic psychotherapy within 30 days from screening or plans to initiate such therapy during the study (supportive therapy, marital therapy and bereavement counseling are allowed).
9. The participant has a significant risk of suicide according to the investigator's clinical judgment or has a score ≥5 on item 10 (suicidal thoughts) of the MADRS or has made a suicide attempt in the previous 6 months.
10. The participant is required to take excluded medications or it is anticipated that the participant will require treatment with at least 1 of the disallowed concomitant medications during the study.
11. The participant has a clinically significant unstable illness, for example hepatic impairment or renal insufficiency, or a cardiovascular, pulmonary, gastrointestinal, endocrine, neurological, rheumatologic, immunologic, hematological, infectious, dermatological disorder or metabolic disturbance.
12. The participant has a history or current diagnosis of Fibromyalgia, Chronic Fatigue Syndrome, Chronic Pain Syndrome and Sleep apnea.
13. The participant has a previous history of cancer that had been in remission for less than 5 years prior to the first dose of study medication. This criterion does not include those participants with basal cell or stage I squamous cell carcinoma of the skin.
14. The participant has 1 or more laboratory value outside the normal range, based on the blood or urine samples taken at the Screening Visit, that are considered by the investigator to be clinically significant; or the participant has any of the following values at the Screening Visit:
* A serum creatinine value \>1.5 times the upper limits of normal (xULN).
* A serum total bilirubin value \>1.5 xULN.
* A serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) value \>2 xULN.
15. The participant has glycosylated hemoglobin (HbA1C) ≥7% at screening and no prior diagnosis of diabetes and/or treatment for diabetes. NOTE: Participants with known diabetes are not excluded.
16. The participant has a thyroid stimulating hormone (TSH) value outside the normal range at the Screening Visit that is deemed clinically significant by the investigator. NOTE: T4 will be checked if TSH is out of range. If T4 is abnormal the participant will be excluded.
17. The participant has clinically significant abnormal vital signs as determined by the investigator.
18. The participant has an abnormal electrocardiogram as determined by the central reader and confirmed as clinically significant by the investigator.
19. The participant has a disease or takes medication that, in the opinion of the investigator, could interfere with the assessments of safety, tolerability, or efficacy.
20. The participant has a positive urine drug screen. NOTE: Positive urine drug screens for benzodiazepines and opiates for which the participant has a valid prescription will be allowed.
21. The participant has a disease or takes medication that, in the opinion of the investigator, could interfere with the assessments of safety, tolerability, or efficacy.
22. The participant has a positive urine drug screen. NOTE: Positive urine drug screens for benzodiazepines and opiates for which the participant has a valid prescription will be allowed.
23. The participant, in the opinion of the investigator, is unlikely to comply with the clinical study protocol or is unsuitable for any reason.
18 Years
75 Years
ALL
No
Sponsors
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Takeda
INDUSTRY
Responsible Party
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Principal Investigators
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Medical Director Clinical Science
Role: STUDY_DIRECTOR
Takeda
Locations
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Birmingham, Alabama, United States
Dothan, Alabama, United States
Muscle Shoals, Alabama, United States
Phoenix, Arizona, United States
Little Rock, Arkansas, United States
Bellflower, California, United States
Costa Mesa, California, United States
Garden Grove, California, United States
Harbor City, California, United States
Huntington Park, California, United States
Irvine, California, United States
Lomita, California, United States
Long Beach, California, United States
Los Angeles, California, United States
Murrieta, California, United States
National City, California, United States
Oceanside, California, United States
Orange, California, United States
Paramount, California, United States
Rancho Cucamonga, California, United States
Redondo Beach, California, United States
Riverside, California, United States
Sacramento, California, United States
San Diego, California, United States
San Jose, California, United States
San Ramon, California, United States
Sherman Oaks, California, United States
Torrance, California, United States
Wildomar, California, United States
Colorado Springs, Colorado, United States
Denver, Colorado, United States
Norwalk, Connecticut, United States
Washington D.C., District of Columbia, United States
Clearwater, Florida, United States
Coral Gables, Florida, United States
Coral Springs, Florida, United States
Edgewater, Florida, United States
Hialeah, Florida, United States
Jacksonville, Florida, United States
Leesburg, Florida, United States
Miami, Florida, United States
Miami Beach, Florida, United States
Miami Lakes, Florida, United States
Orange City, Florida, United States
Orlando, Florida, United States
Pembroke Pines, Florida, United States
Plantation, Florida, United States
Port Charlotte, Florida, United States
Saint Cloud, Florida, United States
Tampa, Florida, United States
Vero Beach, Florida, United States
Atlanta, Georgia, United States
Dunwoody, Georgia, United States
East Point, Georgia, United States
Smyrna, Georgia, United States
Suwanee, Georgia, United States
Honolulu, Hawaii, United States
Chicago, Illinois, United States
Chicago, Illinois, United States
Gurnee, Illinois, United States
Libertyville, Illinois, United States
Skokie, Illinois, United States
Brownsburg, Indiana, United States
Manhattan, Kansas, United States
Topeka, Kansas, United States
Wichita, Kansas, United States
Elizabethtown, Kentucky, United States
Lexington, Kentucky, United States
Paducah, Kentucky, United States
Mandeville, Louisiana, United States
Metairie, Louisiana, United States
Baltimore, Maryland, United States
Boston, Massachusetts, United States
Fall River, Massachusetts, United States
Bloomfield Hills, Michigan, United States
Detroit, Michigan, United States
Kalamazoo, Michigan, United States
Flowood, Mississippi, United States
Hazelwood, Missouri, United States
Saint Charles, Missouri, United States
St Louis, Missouri, United States
Washington, Missouri, United States
Lincoln, Nebraska, United States
Las Vegas, Nevada, United States
Cherry Hill, New Jersey, United States
Albuquerque, New Mexico, United States
Brooklyn, New York, United States
Cedarhurst, New York, United States
Fresh Meadows, New York, United States
New York, New York, United States
Rochester, New York, United States
Staten Island, New York, United States
Charlotte, North Carolina, United States
Columbiana, North Carolina, United States
Durham, North Carolina, United States
Greensboro, North Carolina, United States
Raleigh, North Carolina, United States
Salisbury, North Carolina, United States
Wilmington, North Carolina, United States
Fargo, North Dakota, United States
Cincinnati, Ohio, United States
Cleveland, Ohio, United States
Dayton, Ohio, United States
Franklin, Ohio, United States
Oklahoma City, Oklahoma, United States
Portland, Oregon, United States
Allentown, Pennsylvania, United States
Duncansville, Pennsylvania, United States
Harleysville, Pennsylvania, United States
McMurray, Pennsylvania, United States
Media, Pennsylvania, United States
Philadelphia, Pennsylvania, United States
Pittsburgh, Pennsylvania, United States
Lincoln, Rhode Island, United States
Columbia, South Carolina, United States
Greer, South Carolina, United States
Old Point Station, South Carolina, United States
Clarksville, Tennessee, United States
Knoxville, Tennessee, United States
Memphis, Tennessee, United States
Austin, Texas, United States
Bellaire, Texas, United States
Corpus Christi, Texas, United States
Dallas, Texas, United States
Irving, Texas, United States
Nassau Bay, Texas, United States
Plano, Texas, United States
San Antonio, Texas, United States
Bountiful, Utah, United States
Newport News, Virginia, United States
Norfolk, Virginia, United States
Richmond, Virginia, United States
Virginia Beach, Virginia, United States
Kirkland, Washington, United States
Richland, Washington, United States
Seattle, Washington, United States
Clarksburg, West Virginia, United States
Milwaukee, Wisconsin, United States
Buenos Aires, , Argentina
Córdoba, , Argentina
Mendoza, , Argentina
Santa Fe, , Argentina
Antofagasta, , Chile
Arauco, , Chile
Elqui, , Chile
Santiago, , Chile
Bello, Antioquia, Colombia
Antioquia, , Colombia
Barranquilla, , Colombia
Bogotá, , Colombia
Mexicali, Estado de Baja California, Mexico
León, Guanajuato, Mexico
Mexico City, Mexico City, Mexico
Monterrey, Nuevo León, Mexico
Mérida, Yucatán, Mexico
México, , Mexico
Countries
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References
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Mahableshwarkar AR, Calabrese JR, Macek TA, Budur K, Adefuye A, Dong X, Hanson E, Sachs GS. Efficacy and safety of sublingual ramelteon as an adjunctive therapy in the maintenance treatment of bipolar I disorder in adults: A phase 3, randomized controlled trial. J Affect Disord. 2017 Oct 15;221:275-282. doi: 10.1016/j.jad.2017.06.044. Epub 2017 Jun 20.
Related Links
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Other Identifiers
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U1111-1124-4675
Identifier Type: REGISTRY
Identifier Source: secondary_id
TAK-375SL_203
Identifier Type: -
Identifier Source: org_study_id
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