Facilitation of Zolpidem (≥10 mg) Discontinuation Through Use of Ramelteon in Subjects With Chronic Insomnia - Full Text View

Sponsor:	Takeda Global Research & Development Center, Inc.
Information provided by:	Takeda Global Research & Development Center, Inc.
ClinicalTrials.gov Identifier:	NCT00492232

Purpose

The purpose of this study is to assess whether once-daily ramelteon administration can facilitate the discontinuation of zolpidem in subjects with chronic insomnia.

Condition	Intervention	Phase
Chronic Insomnia	Drug: Ramelteon and zolpidem Drug: Placebo and zolpidem	Phase IV

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	Randomized, Double Blind, Placebo-Controlled Study to Assess Whether the Administration of Ramelteon Could Facilitate the Discontinuation of Zolpidem (Ambien®) ≥10 mg Therapy in Subjects With Chronic Insomnia

Resource links provided by NLM:

Drug Information available for: Zolpidem Ramelteon

U.S. FDA Resources

Further study details as provided by Takeda Global Research & Development Center, Inc.:

Primary Outcome Measures:

Percentage of Subjects Who Discontinued Zolpidem Therapy [ Time Frame: Week 10 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Change From Baseline in Weekly Zolpidem Dosage During Weeks 1-2 [ Time Frame: Baseline and Weeks 1-2 ] [ Designated as safety issue: No ]
Change From Baseline in Weekly Zolpidem Dosage During Weeks 3-4 [ Time Frame: Baseline and Weeks 3-4 ] [ Designated as safety issue: No ]
Change From Baseline in Weekly Zolpidem Dosage During Weeks 5-6 [ Time Frame: Baseline and Weeks 5-6 ] [ Designated as safety issue: No ]
Change From Baseline in Weekly Zolpidem Dosage During Weeks 7-8 [ Time Frame: Baseline and Weeks 7-8 ] [ Designated as safety issue: No ]
Change From Baseline in Weekly Zolpidem Dosage During Weeks 9-10 [ Time Frame: Baseline and Weeks 9-10 ] [ Designated as safety issue: No ]
Change From Baseline in Weekly Zolpidem Frequency During Weeks 1-2 [ Time Frame: Baseline and Weeks 1-2 ] [ Designated as safety issue: No ]
Change From Baseline in Weekly Zolpidem Frequency During Weeks 3-4 [ Time Frame: Weeks 3-4 ] [ Designated as safety issue: No ]
Change From Baseline in Weekly Zolpidem Frequency During Weeks 5-6 [ Time Frame: Weeks 5-6 ] [ Designated as safety issue: No ]
Change From Baseline in Weekly Zolpidem Frequency During Weeks 7-8 [ Time Frame: Baseline and Weeks 7-8 ] [ Designated as safety issue: No ]
Change From Baseline in Weekly Zolpidem Frequency During Weeks 9-10 [ Time Frame: Baseline and Weeks 9-10 ] [ Designated as safety issue: No ]
Subjects Who Completely Discontinued Zolpidem at the End of Double-Blind Treatment Period, by Method of Discontinuation [ Time Frame: Weeks 1-10 ] [ Designated as safety issue: No ]
Subjects Who Achieved a 50% Reduction in Zolpidem Dosage at the End of the Double-Blind Treatment Period [ Time Frame: Baseline and Week 10 ] [ Designated as safety issue: No ]
Subjects Who Achieved a 50% Reduction in Zolpidem Dosage at Any Time During the Double-Blind Treatment Period [ Time Frame: Baseline and Weeks 1-10 ] [ Designated as safety issue: No ]

Enrollment:	135
Study Start Date:	April 2007
Study Completion Date:	May 2008
Primary Completion Date:	March 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental	Drug: Ramelteon and zolpidem Ramelteon 8 mg, tablets, orally, once daily and current zolpidem therapy incrementally reduced by dose, frequency, or both for up to 10 weeks.
2: Placebo Comparator	Drug: Placebo and zolpidem Ramelteon placebo-matching tablets, orally, once daily and current zolpidem therapy incrementally reduced by dose, frequency, or both for up to 10 weeks.

Detailed Description:

Approximately 60 to 70 million adults in the United States alone are affected by insomnia. Daytime symptoms of insomnia include tiredness, lack of energy, difficulty concentrating, and irritability. Recent epidemiologic research focusing on the quality of life has identified significant insomnia-related morbidities that relate to work productivity, health care utilization, and risk of depression. Insomnia is associated with diminished work output, absenteeism, and greater rates of accidents.

Zolpidem is the most commonly prescribed hypnotic in the United States for patients suffering from insomnia.

The purpose of this study is to assess whether ramelteon therapy can facilitate the discontinuation of benzodiazepine therapy in long term users. Subject participation in this study is anticipated to be about 17 weeks.

Subjects were screened and enrolled in a 4-week placebo run-in period, may have been randomized to a 10-week double-blind treatment period, and may have completed with a 2-week open-label treatment period. In the double-blind treatment period, subjects were randomized to one of two treatments: either ramelteon 8 mg tablets taken orally once-daily with concomitant current zolpidem therapy or to placebo-matching tablets once daily with concomitant current zolpidem therapy. Subjects incrementally reduced zolpidem therapy by dose, frequency, or both for up to 10 weeks. Only those subjects who completed the double-blind treatment period and had achieved a 50% reduction in zolpidem therapy during the double-blind treatment period participated in the open-label treatment period in which 8 mg ramelteon was administered. Zolpidem consumed during the open-label treatment period was recorded.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria

Chronic insomnia and taking greater than or equal to 10 mg zolpidem at least 4 times per week.
Has been prescribed zolpidem for difficulty in initiating sleep.
Must report chronic use of zolpidem greater than or equal to10 mg therapy for a minimum of 3 months prior to entry into Period 1 of the study.
Must have taken zolpidem greater than or equal to 10 mg therapy for at least 4 of 7 days each week of the 4 weeks immediately prior to entry into the double blind phase, Period 2.
Expressed a willingness to discontinue zolpidem therapy.
Habitual bedtime is between 9:00 PM and 1:00 AM based on sleep history.
Negative test result for hepatitis B surface antigen and hepatitis C virus antibody.
Females of childbearing potential who are sexually active must agree to use adequate contraception, and can neither be pregnant nor lactating from Screening throughout the duration of the study.

Exclusion Criteria

Known hypersensitivity to ramelteon, zolpidem, or melatonin.
Participated in any other investigational study and/or taken any investigational drug within 30 days prior to the first dose of run-in study medication.
Sleep schedule changes required by employment (eg, shift worker) within 3 months prior to the first night of run-in study medication.
History of fibromyalgia, history of seizures, sleep apnea, restless leg syndrome, periodic leg syndrome, chronic obstructive pulmonary disease, schizophrenia, bipolar disorder, mental retardation, or cognitive disorder.
History of drug addiction or drug abuse within the past 12 months.
History of alcohol abuse within the past 12 months, as defined in Diagnostic and Statistical Manual of Mental Disorders, 4th Edition revised and/or regularly consumes more than 2 alcoholic drinks per day.
Current significant hepatic, renal, endocrine, cardiovascular, gastrointestinal, pulmonary, hematological, or metabolic disease, unless currently controlled and stable with protocol-allowed medication, within 30 days prior to the first night of run-in study medication.
Body mass index of less than 18 or greater than 34 (weight /height2).
Any clinically important abnormal finding as documented by a medical history, physical examination, electrocardiogram, or clinical laboratory tests, as determined by the investigator.
Positive hepatitis panel.
Known history of human immunodeficiency virus.
Any additional conditions(s) that in the investigator's opinion would affect:
- sleep/wake function
- prohibit the subject from completing the study
- indicate that continuation in the study would not be in the best interests of the subject.
Is required to take or continues taking any disallowed medication, prescription medication, herbal treatment or over-the counter medication, including:
- Melatonin
- Anxiolytics
- Antipsychotics
- Over-the-counter and prescription sedatives
- Hypnotics (excluding zolpidem)
- Narcotic analgesics
- Antidepressants
- Beta-blockers (exception is that Atenolol is permissible)
- Anticonvulsants
- St. John's wort
- Sedating H1 antihistamines
- Kava-kava
- Systemic steroids
- Ginkgo-biloba
- Respiratory stimulants
- Over-the-counter and prescription diet aids
- Sedating Decongestants

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00492232

Show 41 Study Locations

Sponsors and Collaborators

Takeda Global Research & Development Center, Inc.

Investigators

Study Director:

Medical Director Clinical Science

Takeda Global Research & Development Center

More Information

Additional Information:

Rozerem Package Insert This link exits the ClinicalTrials.gov site

FDA Safety Alerts and Recalls This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Takeda Global Research & Development Center, Inc. ( Sr. VP, Clinical Science )
Study ID Numbers:	01-06-TL-375-071
Study First Received:	June 25, 2007
Results First Received:	May 28, 2009
Last Updated:	August 17, 2009
ClinicalTrials.gov Identifier:	NCT00492232 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by Takeda Global Research & Development Center, Inc.:

Chronic Insomnia
Sleep Initiation and Maintenance Disorder
Drug Therapy

Additional relevant MeSH terms:

Sleep Initiation and Maintenance Disorders
Zolpidem
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Nervous System Diseases
Physiological Effects of Drugs
Central Nervous System Depressants
Dyssomnias
Sleep Disorders

Pharmacologic Actions
Sleep Disorders, Intrinsic
Mental Disorders
Therapeutic Uses
GABA Agonists
Hypnotics and Sedatives
GABA Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on February 08, 2010