- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00383643
Xyrem(Sodium Oxybate) and Ambien(Zolpidem Tartrate) in the Treatment of Chronic Insomnia.
Xyrem(Sodium Oxybate) and Ambien(Zolpidem Tartrate) in the Treatment of Chronic Insomnia: A Randomized, Double-Blind, Double-Dummy, Placebo-Controlled, Parallel-Group Study.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Primary aim:
1. To assess the long term efficacy of sodium oxybate and zolpidem tartrate in reducing insomnia and improving sleep quality as assessed by a range of self-reported measures.
Questionnaires and Rating Scales: Subjects completed the following questionnaires and scales: Insomnia Severity Index, Epworth Sleepiness Scale (ESS), Beck Depression Inventory, Pittsburgh Sleep Quality Index (PSQI), Profile of Mood States-Fatigue (POMS). These questionnaires were administered at study baseline, treatment week 4, 8 and 12.
Clinical Global Impression (CGI). The CGI is a clinician-rated scale composed of two subscales that measure disease severity and degree of change, respectively. CGI-Severity (CGI-S) is a single-item, global scale of disease severity that requires the investigator to compare the patient's symptoms with those of all other patients who have the disorder. It is scored from 1 (normal) to 6 (among the most extremely ill of patients). CGI-Change (CGI-C) is a single-item scale of symptomatic improvement or worsening that requires the investigator to compare the patient's status at the time of assessment with baseline severity (baseline CGI-S). One study investigator performed all CGI-S and CGI-C ratings for all subjects.
Randomization. After completing all baseline procedures, eligible subjects were randomized to receive either a combination of active SXB and placebo ZOL (pZOL), active ZOL and placebo SXB (pSXB), or pSXB and pZOL, in a 1:1:1 parallel double-dummy design. A member of the study team who had no contact with subjects and no other role in this study was responsible for preparing study medications according to a randomization schedule. ZOL was encapsulated in lactose powder filled gelatin capsules to be indistinguishable from placebo capsules. Liquid pSXB was designed to match active SXB in appearance, taste and consistency. Subjects were given both liquid and capsule study medications, to maintain the double dummy design. Due to the flexible dose design of this study, subjects and investigators were not blinded to the dosages of study medication/placebo. All subjects were instructed to start study medication at 2.25 grams of SXB/pSXB and 5mg of ZOL/pZOL at bedtime. One study investigator reviewed all potential known side effects of SXB and ZOL prior to dosing, and subjects were instructed to take study medications at the bedside immediately before attempting to sleep, as is the standard administration for SXB.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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California
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Stanford, California, United States, 94305
- Stanford University School of Medicine
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Written informed consent is obtained.
- The patient is an outpatient, man or woman of any ethnic origin, 18-75 years of age (inclusive).
- Patient reports insomnia for at least six months, and insomnia causes the patient distress.
- The Investigator determines that the patient meets diagnostic criteria for Chronic Insomnia according to International Classification of Sleep Disorders (ICSD) criteria.
- Sleep diary based screening shows sleep onset latency >30 minutes, and /or wake after sleep onset >30 minutes per night at least 3 nights per week, with combined wake-time-in-bed _> 45 minutes.
- The patient is in good health as determined by a medical and psychiatric history, and physical examination.
- Women must be surgically sterile, 2 years post-menopausal, or if of child-bearing potential, using a medically accepted method of birth control, and agree to continued use of this method for the duration of the study.
- The patient is willing and able to comply with study restrictions and to attend regularly scheduled clinic visits as specified in this protocol.
Exclusion Criteria:
- Has any clinically significant, uncontrolled medical or psychiatric conditions. (treated or untreated)
- Has a probable diagnosis of a current sleep disorder other than Chronic Insomnia.
- Used any prescription drugs disallowed by the protocol or clinically significant use of over-the counter(OTC) drugs within 14 days before the screening visit.
- Has a history of alcohol, narcotic, or any other abuse as defined by the DSM-V.
- Has a clinically significant deviation from normal in the physical examination.
- Is a pregnant or lactating woman. (Any woman becoming pregnant during the study will be withdrawn from the study.)
- Has any disorder that may interfere with drug absorption, distribution, metabolism, or excretion (including gastrointestinal surgery and succinic semialdehyde dehydrogenase deficiency)
- Has a known clinically significant drug sensitivity to sodium oxybate or sedative hypnotics.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Placebo Comparator: Placebo
Eligible subjects randomized to this arm received placebo as gelatin capsule and a liquid capsule to fully maintain the blind.
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Other Names:
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Active Comparator: Zolpidem tartrate
Eligible subjects randomized to this arm received zolpidem as gelatin capsule and a placebo liquid capsule to fully maintain the blind.
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Other Names:
Other Names:
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Active Comparator: Sodium oxybate
Eligible subjects randomized to this arm received placebo as gelatin capsule and a sodium oxybate capsule to fully maintain the blind.
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Other Names:
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Assessment of Clinical Global Impression-change.
Time Frame: Baseline to week 12
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Clinician assessment of Clinical Global Impression-Change score at week 12 of treatment intervention.
The Clinical Global Impression - Change scale is a 7 point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the current time point.
It is rated as: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse.
One one clinician provided the ratings in this trial.
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Baseline to week 12
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Assessment of Insomnia Severity Index
Time Frame: 12 weeks
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Current self-report on Insomnia Severity Index at week 12 of treatment intervention. This is a seven-item questionnaire where the sum of the answers indicate the severity of insomnia. Total score categories: 0-7 = No clinically significant insomnia 8-14 = Subthreshold insomnia 15-21 = Clinical insomnia (moderate severity) 22-28 = Clinical insomnia (severe) |
12 weeks
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Assessment of Pittsburgh Sleep Quality Index (PSQI)
Time Frame: One month
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Current self-report on Pittsburgh Sleep Quality Index (PSQI) at week 12 of intervention. Consisting of 19 items, the PSQI measures several different aspects of sleep which can be combined into one global score. Each item measure is scored on a scale of 0 to 3 where 3 is the extreme negative. The composite PSQI score is then calculated by totaling the seven component scores, providing an overall score ranging from 0 to 21, where lower scores denote a healthier sleep quality. Based on this questionnaire, a composite score of 5 or greater is indicative of poor sleep quality. |
One month
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Assessment of Fatigue
Time Frame: One month
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Current self-report on Profile of Mood State -- Fatigue (POMS-F) at week 12 of intervention.
This subscale of the POMS consists of 7 items each scored on a scale of 0 (not at all) to 4 (extremely) which are summed to provide a composite score of fatigue.
The range is 0 to 28 for this subscale.
Higher scores indicate more fatigue.
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One month
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Assessment of Sleepiness
Time Frame: One month
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Current self-report on Epworth Sleepiness Scale (ESS) at week 12 of intervention.
This measure consists of 8 scenarios in which the participant is asked to assess how likely s/he is to fall asleep.
Scale: 0 = would never doze; 1 = slight chance of dozing; 2 = moderate chance of dozing; 3 = high chance of dozing.
Responses are summed for a total score ranging from 0 to 24.
The higher the score, the greater the self-reported sleepiness.
Scores of 9 and below are considered in the normal range.
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One month
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Jed E Black, MD, Stanford University
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Mental Disorders
- Nervous System Diseases
- Sleep Disorders, Intrinsic
- Dyssomnias
- Sleep Wake Disorders
- Sleep Initiation and Maintenance Disorders
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Central Nervous System Depressants
- Anesthetics, Intravenous
- Anesthetics, General
- Anesthetics
- Hypnotics and Sedatives
- Adjuvants, Anesthesia
- GABA Agents
- Sleep Aids, Pharmaceutical
- GABA-A Receptor Agonists
- GABA Agonists
- Zolpidem
- Sodium Oxybate
Other Study ID Numbers
- 95900
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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