Trial Comparing Effects of Xyrem Taken Orally and Modafinil With Placebo in Treating Daytime Sleepiness in Narcolepsy

Study Overview
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Brief Summary
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This study will be conducted as a randomized, double blind, double-dummy, placebo-controlled, parallel-group trial in patients diagnosed with narcolepsy. Volunteers for this trial will be required to make 5 visits over up to 14 weeks to a participating expert physician practitioner for various sleep and narcolepsy evaluations and diaries will also be collected. Participants will take assigned medications during the course of the trial. Subjects will have a 25% probability of receiving placebo for both drugs (modafinil and Xyrem). All subject volunteers must meet criteria for narcolepsy and have evidence of daytime sleepiness. Patients will not incur any personal medical expenses due to participation in this trial. The sponsor is covering all visit costs not covered by insurance and there are some funds for patient expenses such as travel.

Official Title
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Randomized, Double-Blind, Double-Dummy, Placebo-Controlled, Parallel-Group, Multi-Center Trial Comparing the Effects of Orally Administered Xyrem (Sodium Oxybate) and Modafinil With Placebo in Treatment of Daytime Sleepiness in Narcolepsy

Conditions
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Narcolepsy

Intervention / Treatment
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* Drug: Xyrem
* Drug: Xyrem Placebo
* Drug: Modafinil at established dose
* Drug: Modafinil (Placebo)


Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA Patients will be included in the trial if they: Have signed and dated an informed consent prior to beginning protocol required procedures. Are willing and able to complete the entire trial as described in the protocol. Are 18 years of age or older. Fulfill the International Classification of Sleep Disorders criteria for the diagnosis of narcolepsy. Are taking stable doses of modafinil (200 to 600 mg/day) for the treatment of daytime sleepiness for a period of three months or greater and the modafinil dose has been stable for at least 1 month prior to entering this trial Females may be included who are surgically sterile, two years post-menopausal, or if of child-bearing potential, using a medically accepted method of birth control (e.g., barrier method with spermicide, oral contraceptive, or abstinence) and agree to continue use of this method for the duration of the trial. In the opinion of the investigator have adequate support for the duration of the trial to include transportation to and from the trial site. In addition, if in the investigator's assessment it is clinically indicated, the patient is willing to not operate a car or heavy machinery for the duration of the trial or for as long as the investigator deems clinically indicated. EXCLUSION CRITERIA Patients will be excluded from the trial if they: Have received gamma-hydroxybutyrate in the last 30 days. Have taken any investigational therapy within the 30-day period prior to the initial screening visit (Visit 1) for this trial. Have sleep apnea syndrome, defined as an Apnea Index > 10 per hour or an AHI (Apnea Hypopnea Index) greater than 15 per hour, or have any other cause of daytime sleepiness, and have any other disorder(s) that can be considered a primary cause of excessive daytime sleepiness (e.g., severe periodic leg movement syndrome as determined by the investigator, sleep apnea, sleep deprivation). Are taking hypnotics, tranquilizers, antihistamines (except for non-sedating antihistamines), benzodiazepines or clonidine at the start of the baseline period. Patients taking anticonvulsants are not eligible to participate event if they are willing to washout anticonvulsants for the trial. Are experiencing any major illness, including unstable cardiovascular, endocrine, neoplastic, gastrointestinal, hematologic, hepatic, immunologic, metabolic, neurological (other than narcolepsy/cataplexy), pulmonary, and/or renal disease which would place the patient at risk during the trial or compromise the objectives outlined in the protocol. Have psychiatric disorders, major affective or psychotic disorders, or other problems that, in the investigator's opinion, would preclude the patient's participation and completion of this trial or compromise reliable representation of subjective symptoms. Have a current or recent (within one year) history of a substance use disorder including alcohol abuse as defined by the DSM-IV. Have a serum creatinine greater than 2.0 mg/dL, abnormal liver function tests (SGOT [AST] or SGPT [ALT] more than twice the upper limit of normal), or elevated serum bilirubin (more than 1.5 times the upper limit of normal), or pre-trial ECG results demonstrating clinically significant arrhythmias, greater than a first degree AV block or a history of myocardial infarction within the last six months. Have an occupation that requires variable shift work or routine night shift. Have a clinically significant history of seizure disorder either past or present, a history of clinically significant head trauma (i.e., concussion resulting in clinically significant loss of consciousness) or past invasive intracranial surgery, and are taking anticonvulsant medications.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1.<br>Xyrem + Modafinil Placebo | Drug: Xyrem<br>* Xyrem oral solution at 6 g/day for 4 weeks and 9 g/day for another 4 weeks.<br>* Other names: Sodium Oxybate;Drug: Modafinil (Placebo)<br>* Modafinil Placebo oral capsules 1 to 3 capsules per day for 8 weeks.<br>* Other names: Provigil Placebo;|
| Placebo Comparator: Group 2:<br>Xyrem Placebo + Modafinil Placebo | Drug: Xyrem Placebo<br>* Xyrem Placebo oral solution 12 ml per day for 4 weeks and 18 ml per day for another 4 weeks.<br>* Other names: Sodium Oxybate Placebo;Drug: Modafinil (Placebo)<br>* Modafinil Placebo oral capsules 1 to 3 capsules per day for 8 weeks.<br>* Other names: Provigil Placebo;|
| Active Comparator: Group 3<br>Xyrem Placebo + Modafinil at established dose | Drug: Xyrem Placebo<br>* Xyrem Placebo oral solution 12 ml per day for 4 weeks and 18 ml per day for another 4 weeks.<br>* Other names: Sodium Oxybate Placebo;Drug: Modafinil at established dose<br>* Modafinil oral capsules at 200 to 600 mg per day for 8 weeks.<br>* Other names: Provigil;|
| Experimental: Group 4:<br>Xyrem + Modafinil at established dose | Drug: Xyrem<br>* Xyrem oral solution at 6 g/day for 4 weeks and 9 g/day for another 4 weeks.<br>* Other names: Sodium Oxybate;Drug: Modafinil at established dose<br>* Modafinil oral capsules at 200 to 600 mg per day for 8 weeks.<br>* Other names: Provigil;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Daytime Sleep Latency as Measured by the Maintenance of Wakefulness Test (MWT) | The Maintenance of Wakefulness Test consisted of four 20 minute tests of the patient's ability to remain awake in soporific conditions. The Mean change from baseline to week 8 in the average MWT number of minutes until sleep onset was the primary endpoint. | Baseline to Week 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Narcolepsy, Daytime Sleepiness, Daytime sleepiness in narcolepsy