Safety of Ramelteon in Subjects With Mild to Moderate Obstructive Sleep Apnea - Full Text View

Sponsor:	Takeda Global Research & Development Center, Inc.
Information provided by:	Takeda Global Research & Development Center, Inc.
ClinicalTrials.gov Identifier:	NCT00672061

Purpose

The purpose of this study is to assess the safety of ramelteon, once daily (QD), in individuals with obstructive sleep apnea.

Condition	Intervention	Phase
Sleep Apnea, Obstructive	Drug: Ramelteon or Placebo	Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Crossover Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Phase II Safety Study of TAK-375 in Subjects With Mild to Moderate Obstructive Sleep Apnea

Resource links provided by NLM:

MedlinePlus related topics: Oxygen Therapy Sleep Apnea

Drug Information available for: Ramelteon

U.S. FDA Resources

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

Primary Outcome Measures:

Apnea Hypopnea Index measured by Respiratory Inductance Plethysmography (RIP) [ Time Frame: Periods 1 and 2. ] [ Designated as safety issue: Yes ]
Central Apnea Index. [ Time Frame: Periods 1 and 2. ] [ Designated as safety issue: Yes ]
Mean Oxygen Saturation for the entire night. [ Time Frame: Periods 1 and 2. ] [ Designated as safety issue: Yes ]
Obstructive Apnea Index. [ Time Frame: Periods 1 and 2. ] [ Designated as safety issue: Yes ]
Hypopnea Index. [ Time Frame: Periods 1 and 2. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Mean Oxygen Saturation for the entire night. [ Time Frame: Periods 1 and 2. ] [ Designated as safety issue: Yes ]
Oxygen Saturation Means for Awake Sleep Stage. [ Time Frame: Periods 1 and 2. ] [ Designated as safety issue: Yes ]
Oxygen Saturation Means for Non-Rapid Eye Movement Sleep Stage. [ Time Frame: Periods 1 and 2. ] [ Designated as safety issue: Yes ]
Oxygen Saturation Means for Rapid Eye Movement Sleep Stage. [ Time Frame: Periods 1 and 2. ] [ Designated as safety issue: Yes ]
Percentage of oxygen saturation is less than 80%. [ Time Frame: Periods 1 and 2. ] [ Designated as safety issue: Yes ]
Latency to Persistent Sleep. [ Time Frame: Periods 1 and 2. ] [ Designated as safety issue: No ]
Total Sleep Time. [ Time Frame: Periods 1 and 2. ] [ Designated as safety issue: No ]
Sleep Efficiency. [ Time Frame: Periods 1 and 2. ] [ Designated as safety issue: No ]
Awake Time after Persistent Sleep. [ Time Frame: Periods 1 and 2. ] [ Designated as safety issue: No ]
Number of Awakenings after Persistent Sleep. [ Time Frame: Periods 1 and 2. ] [ Designated as safety issue: No ]
Subjective Sleep Latency. [ Time Frame: Crossover Period 1 AM; Crossover Period 2 AM ] [ Designated as safety issue: No ]
Subjective Total Sleep Time. [ Time Frame: Periods 1 and 2. ] [ Designated as safety issue: No ]
Subjective Sleep Quality. [ Time Frame: Periods 1 and 2. ] [ Designated as safety issue: No ]
Subjective Number of Awakenings. [ Time Frame: Periods 1 and 2. ] [ Designated as safety issue: No ]
Subjective Ease of Falling Back to Sleep after Awakening. [ Time Frame: Periods 1 and 2. ] [ Designated as safety issue: No ]
Subjective Level of Alertness. [ Time Frame: Periods 1 and 2. ] [ Designated as safety issue: No ]
Subjective Ability to Concentrate. [ Time Frame: Periods 1 and 2. ] [ Designated as safety issue: No ]
Percentage of Total Sleep Time in REM sleep [ Time Frame: Periods 1 and 2. ] [ Designated as safety issue: No ]
Percentage of Total Sleep Time in Stage 1 NREM sleep [ Time Frame: Periods 1 and 2. ] [ Designated as safety issue: No ]
Percentage of Total Sleep Time in Stage 2 NREM sleep [ Time Frame: Periods 1 and 2. ] [ Designated as safety issue: No ]
Percentage of Total Sleep Time in Stage 3/4 NREM sleep [ Time Frame: Periods 1 and 2. ] [ Designated as safety issue: No ]
Percentage of Total Sleep Time in latency to REM as determined by polysomnography [ Time Frame: Periods 1 and 2. ] [ Designated as safety issue: No ]

Enrollment:	26
Study Start Date:	July 2003
Study Completion Date:	December 2003
Primary Completion Date:	December 2003 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Ramelteon 16 mg QD or Placebo QD	Drug: Ramelteon or Placebo Ramelteon 16 mg, tablet, orally, once daily for Periods 1 or 2 and ramelteon placebo-matching tablets, orally, once daily for Periods 1 or 2. Other Names: Rozerem ramelteon TAK-375

Detailed Description:

Insomnia is characterized by difficulties initiating and maintaining sleep, or complaints of non-restorative and non-refreshing sleep. Transient insomnia affects approximately one-third to one-half of the US population, based on the results of 2 surveys of representative samples of the adult US population conducted by the Gallup Organization in which respondents were asked if they had "ever had difficulty sleeping." Based on reports of "regular" or "frequent" sleep difficulty, results from the same studies suggest that approximately one-tenth of the US population experiences chronic insomnia. The ideal treatment for insomnia would reduce the latency to onset of sleep and increase total sleep time, without a negative impact on sleep architecture and without safety concerns or next-day effects.

Ramelteon is under global development by Takeda Chemical Industries, Ltd., for the treatment of transient and chronic insomnia and for the treatment of Circadian Rhythm Sleep Disorders.

This study is being conducted to assess the safety of Ramelteon in subjects with obstructive sleep apnea. Participation this this study is anticipated to be about 1.5 months.

Eligibility

Ages Eligible for Study:	21 Years to 64 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria

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.
Clinical history of chronic obstructive pulmonary disease and a confirmatory diagnosis based on pulmonary function tests at screening.
Moderate: forced expiratory volume in one second/ forced vital capacity less than 70% and forced expiratory volume 135-75% of predicted.
Post-bronchodilator forced expiratory volume in one second change from baseline of less than 12%.
Negative chest x-ray at screening, other than findings consistent with mild to moderate chronic obstructive pulmonary disease, within the last 6 months.
Arterial oxygen saturation during sleep greater than 85% for at least 99% of the recording period, with no arterial oxygen saturation readings less than 80% as assessed by pulse oximetry at polysomnography screening.
Arterial oxygen saturation during wakefulness greater than 91% (both supine and sitting) as assessed by pulse oximetry at screening.
Habitual bedtime is between 8:30 p.m. and 12:00 a.m.
Body mass index between 18 and 34, inclusive.
Agrees to remain in the study center for three overnight stays.

Exclusion Criteria:

Known hypersensitivity to ramelteon or related compounds, including melatonin.
Known hypersensitivity to Ventolin® or related compounds.
Previously participated in a study involving ramelteon.
Participated in any other investigational study and/or taken any investigational drug within 30 days or five half-lives prior to Day 1 of study medication, whichever is longer.
Clinical history of acute or chronic respiratory failure, severe chronic obstructive pulmonary disease, or hypercapnia (Partial Pressure of Oxygen in Arterial Blood greater than or equal to45 mmHg).
History of or currently has right ventricular hypertrophy on electrocardiogram or right heart failure.
Periodic leg movement with arousal index (per hour of sleep) greater than 20 as seen at polysomnography screening.
Apnea hypopnea index greater than 15 as seen at polysomnography screening.
Acute clinically significant illness within 2 weeks or has been hospitalized within 4 weeks of study participation.
Sleep schedule changes required by employment within three months prior to Day 1 of study medication, or has flown across greater than three time zones within seven days prior to screening.
Participated in a weight loss program or has substantially altered their exercise routine within 30 days prior to Day 1 of study medications.
History of seizures, sleep apnea, restless leg syndrome, period limb movement disorder, other known sleep disorders, schizophrenia, bipolar disease, mental retardation, or cognitive disorder.
History of psychiatric disorder within the past 12 months.
History of drug addiction or drug abuse within the past 12 months.
History of alcohol abuse within the past 12 months and/or regularly consumes 4 or more alcoholic drinks per day.
Unable to discontinue the use of hypnotics for the duration of the study.
Any clinically important abnormal finding, other than chronic obstructive pulmonary disease, as determined by medical history, physical examination, electrocardiogram, or clinical laboratory tests, as determined by the investigator.
Current significant neurological, hepatic, renal, endocrine, cardiovascular, gastrointestinal, pulmonary, hematologic, or metabolic disease, unless currently controlled and stable with protocol-allowed medication 30 days prior to Day 1 of study medication.
Hematocrit value greater than 55% at screening.
Positive hepatitis panel.
Any additional condition(s) that in the Investigator's opinion would:
- affect sleep-wake function
- prohibit the subject from completing the study
- not be in the best interest of the subject
Is required to take or continues taking any disallowed medication, prescription medication, herbal treatment or over-the counter medication, including:
- Anxiolytics
- Hypnotics
- Antidepressants
- Anticonvulsants
- Sedating H1 antihistamines
- Systemic steroids
- Decongestants
- Over-the-counter and prescription stimulants
- Over-the-counter and prescription diet aids
- Central nervous system active drugs and narcotic analgesics
- Lipophilic beta blockers
- Melatonin
- St. John's Wort
- Kava-kava
- Gingko biloba

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00672061

Locations

United States, Alabama

Birmingham, Alabama, United States
United States, California

Palm Springs, California, United States

Santa Monica, California, United States
United States, Florida

Winter Park, Florida, United States
United States, Ohio

Cincinnati, Ohio, United States

Sponsors and Collaborators

Takeda Global Research & Development Center, Inc.

Investigators

Study Director:

VP Clinical Science

Takeda Global Research & Development Center, Inc.

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

Publications:

Kryger M, Wang-Weigand S, Roth T. Safety of ramelteon in individuals with mild to moderate obstructive sleep apnea. Sleep Breath. 2007 Sep;11(3):159-64.

Responsible Party:	VP, Clinical Science, Takeda Global Research & Development Center, Inc.
ClinicalTrials.gov Identifier:	NCT00672061 History of Changes
Other Study ID Numbers:	01-03-TL-375-039, U1111-1115-1494
Study First Received:	May 2, 2008
Last Updated:	May 31, 2010
Health Authority:	United States: Food and Drug Administration

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

Sleep Apnea, Obstructive
Insomnia
Drug Therapy

Additional relevant MeSH terms:

Apnea
Sleep Apnea Syndromes
Sleep Apnea, Obstructive
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms, Respiratory

Signs and Symptoms
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Disorders
Nervous System Diseases

ClinicalTrials.gov processed this record on February 09, 2012