Efficacy and Safety of Ramelteon Sublingual in Adult Patients With Acute Depressive Episodes Associated With Bipolar I Disorder

NCT01467700 | Terminated Phase 3 Results

• 2 other identifiers: TAK-375SL_201U1111-1122-7380
• Study Type: interventional
• Target: 490
• Locations: 5 countries
• Sites: 161

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.

Conditions

Acute Depressive Episode

Keywords

Drug Therapy

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at 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.

  Baseline and Week 6

Secondary Outcomes (8)

• 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 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

• Change From Baseline in Clinical Global Impression Scale-Severity (CGI-S) at Week 6

  Baseline and Week 6

Study Arms (4)

Ramelteon SL 0.1 mg

EXPERIMENTAL

Ramelteon SL 0.1 mg, tablets, sublingual (SL) \[dissolved under the tongue\], once daily (QD), every night at bedtime for up to 8 weeks.

Drug: Ramelteon SL

Ramelteon SL 0.4 mg

EXPERIMENTAL

Ramelteon SL 0.4 mg, tablets, sublingual, once daily, every night at bedtime for up to 8 weeks.

Drug: Ramelteon SL

Ramelteon SL 0.8 mg

EXPERIMENTAL

Ramelteon SL 0.8 mg tablets, sublingual, once daily, every night at bedtime for up to 8 weeks.

Drug: Ramelteon SL

Placebo

PLACEBO COMPARATOR

Ramelteon SL placebo-matching, tablets, sublingual, once daily, every night at bedtime for up to 8 weeks.

Drug: Placebo

Interventions

Ramelteon SL DRUG

Ramelteon SL tablets

Also known as: TAK-375SL

Ramelteon SL 0.1 mg; Ramelteon SL 0.4 mg; Ramelteon SL 0.8 mg

Placebo DRUG

Ramelteon placebo-matching tablets

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 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.
• A female participant of childbearing potential who is sexually active and 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.
• 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.

You may not qualify if:

• 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.
• History of Rapid Cycling Bipolar Disorder: Patients who have more than 8 episodes of mood disorder per year.
• The participant experienced the first episode of mood disorder after the age of 65 years.
• The current depressive symptoms of the participant 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 antidepressant medications of at least 6 weeks duration each.
• The participant is on any other psychotropic medications except for lithium (serum levels 0.8 to mEq/L) or valproate (serum levels 50 to 125 mcg/ml) at the Screening visit.
• The participant is on lithium and/or valproate for less than 30 days prior to screening.

Sponsors & Collaborators

• Takeda: lead

Study Sites (161)

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Birmingham, Alabama, United States

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Dothan, Alabama, United States

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Muscle Shoals, Alabama, United States

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Phoenix, Arizona, United States

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Fayetteville, Arkansas, United States

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Little Rock, Arkansas, United States

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Bellflower, California, United States

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Costa Mesa, California, United States

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Garden Grove, California, United States

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Harbor City, California, United States

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Huntington Park, California, United States

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Irvine, California, United States

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Lomita, California, United States

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Long Beach, California, United States

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Los Angeles, California, United States

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Murrieta, California, United States

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National City, California, United States

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Oceanside, California, United States

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Orange, California, United States

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Paramount, California, United States

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Rancho Cucamonga, California, United States

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Redondo Beach, California, United States

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Riverside, California, United States

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Sacramento, California, United States

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San Diego, California, United States

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San Jose, California, United States

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San Ramon, California, United States

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Sherman Oaks, California, United States

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Torrance, California, United States

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Wildomar, California, United States

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Colorado Springs, Colorado, United States

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Denver, Colorado, United States

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Norwalk, Connecticut, United States

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Washington D.C., District of Columbia, United States

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Clearwater, Florida, United States

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Coral Gables, Florida, United States

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Coral Springs, Florida, United States

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Edgewater, Florida, United States

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Hialeah, Florida, United States

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Jacksonville, Florida, United States

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Leesburg, Florida, United States

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Miami, Florida, United States

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Miami Beach, Florida, United States

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Miami Lakes, Florida, United States

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Orange City, Florida, United States

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Orlando, Florida, United States

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Pembroke Pines, Florida, United States

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Plantation, Florida, United States

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Port Charlotte, Florida, United States

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Saint Cloud, Florida, United States

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Tampa, Florida, United States

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Vero Beach, Florida, United States

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Atlanta, Georgia, United States

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Dunwoody, Georgia, United States

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East Point, Georgia, United States

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Smyrna, Georgia, United States

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Suwanee, Georgia, United States

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Honolulu, Hawaii, United States

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Chicago, Illinois, 60610, United States

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Chicago, Illinois, United States

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Gurnee, Illinois, 60610, United States

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Hoffman Estates, Illinois, United States

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Libertyville, Illinois, United States

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Skokie, Illinois, United States

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Brownsburg, Indiana, United States

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Manhattan, Kansas, United States

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Topeka, Kansas, United States

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Wichita, Kansas, United States

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Elizabethtown, Kentucky, United States

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Lexington, Kentucky, United States

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Paducah, Kentucky, United States

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Mandeville, Louisiana, United States

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Metairie, Louisiana, United States

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Baltimore, Maryland, United States

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Boston, Massachusetts, United States

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Fall River, Massachusetts, United States

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Bloomfield Hills, Michigan, United States

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Detroit, Michigan, United States

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Kalamazoo, Michigan, United States

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Flowood, Mississippi, United States

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Hazelwood, Missouri, United States

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Saint Charles, Missouri, United States

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St Louis, Missouri, United States

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Washington, Missouri, United States

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Lincoln, Nebraska, United States

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Las Vegas, Nevada, United States

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Cherry Hill, New Jersey, United States

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Albuquerque, New Mexico, United States

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Brooklyn, New York, United States

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Cedarhurst, New York, United States

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Fresh Meadows, New York, United States

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New York, New York, United States

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Rochester, New York, United States

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Staten Island, New York, United States

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Charlotte, North Carolina, United States

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Columbiana, North Carolina, United States

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Durham, North Carolina, United States

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Greensboro, North Carolina, United States

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Raleigh, North Carolina, United States

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Salisbury, North Carolina, United States

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Wilmington, North Carolina, United States

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Fargo, North Dakota, United States

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Cincinnati, Ohio, United States

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Cleveland, Ohio, United States

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Dayton, Ohio, United States

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Franklin, Ohio, United States

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Oklahoma City, Oklahoma, United States

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Portland, Oregon, United States

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Allentown, Pennsylvania, United States

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Duncansville, Pennsylvania, United States

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Harleysville, Pennsylvania, United States

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McMurray, Pennsylvania, United States

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Media, Pennsylvania, United States

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Philadelphia, Pennsylvania, United States

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Pittsburgh, Pennsylvania, United States

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Lincoln, Rhode Island, United States

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Columbia, South Carolina, United States

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Greer, South Carolina, United States

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Old Point Station, South Carolina, United States

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Clarksville, Tennessee, United States

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Knoxville, Tennessee, United States

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Memphis, Tennessee, United States

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Austin, Texas, United States

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Bellaire, Texas, United States

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Corpus Christi, Texas, United States

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Dallas, Texas, United States

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Houston, Texas, United States

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Irving, Texas, United States

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Nassau Bay, Texas, United States

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Plano, Texas, United States

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San Antonio, Texas, United States

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Bountiful, Utah, United States

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Newport News, Virginia, United States

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Norfolk, Virginia, United States

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Richmond, Virginia, United States

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Virginia Beach, Virginia, United States

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Kirkland, Washington, United States

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Richland, Washington, United States

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Seattle, Washington, United States

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Clarksburg, West Virginia, United States

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Milwaukee, Wisconsin, United States

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Buenos Aires, Argentina

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Córdoba, Argentina

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Mendoza, Argentina

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Santa Fe, Argentina

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Antofagasta, Chile

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Arauco, Chile

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Elqui, Chile

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Santiago, Chile

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Bello, Antioquia, Colombia

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Antioquia, Colombia

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Barranquilla, Colombia

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Bogotá, Colombia

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Mexicali, Estado de Baja California, Mexico

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León, Guanajuato, Mexico

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Mexico City, Mexico City, Mexico

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Monterrey, Nuevo León, Mexico

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San Lucas, Tepetlacalco, Mexico

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Mérida, Yucatán, Mexico

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México, Mexico

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San Luis Potosí City, Mexico

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Related Links

• Rozerem Package Insert

Results Point of Contact

• Title: Medical Director, Clinical Science
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Director Clinical Science

  Takeda

  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: November 4, 2011
• First Posted: November 9, 2011
• Study Start: December 1, 2011
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: May 16, 2016
• Results First Posted: May 16, 2016

Record last verified: 2016-04

Locations

AR (4); ME (8); CO (4); US (141); CL (4)