Narcolepsy
Conditions
Keywords
Narcolepsy, Daytime Sleepiness, Daytime sleepiness in narcolepsy
Brief summary
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.
Interventions
DRUGXyrem
Xyrem oral solution at 6 g/day for 4 weeks and 9 g/day for another 4 weeks.
DRUGXyrem Placebo
Xyrem Placebo oral solution 12 ml per day for 4 weeks and 18 ml per day for another 4 weeks.
DRUGModafinil at established dose
Modafinil oral capsules at 200 to 600 mg per day for 8 weeks.
DRUGModafinil (Placebo)
Modafinil Placebo oral capsules 1 to 3 capsules per day for 8 weeks.
Sponsors
Jazz Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Daytime Sleep Latency as Measured by the Maintenance of Wakefulness Test (MWT) | Baseline to Week 8 | 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. |
Countries
France, Germany, Switzerland, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Xyrem Placebo + Modafinil Placebo Xyrem Placebo volume equivalent to 6 grams per day for the first 4 weeks and 9 grams per day for the remaining 4 weeks + Modafinil Placebo equivalent to prior dosage. | 55 |
| Xyrem + Modafinil Placebo Xyrem 6 grams per day for the first 4 weeks and 9 grams per day for the remaining 4 weeks + Modafinil Placebo equivalent to prior dosage. | 50 |
| Xyrem Placebo + Modafinil at Established Dose Xyrem Placebo volume equivalent to 6 grams per day for the first 4 weeks and 9 grams per day for the remaining 4 weeks + Modafinil at participant's prior dosage. | 63 |
| Xyrem + Modafinil at Established Dose Xyrem 6 grams per day for the first 4 weeks and 9 grams per day for the remaining 4 weeks + Modafinil at participant's prior dosage. | 54 |
| Total | 222 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 4 | 1 | 7 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 | 0 |
| Overall Study | Non-Compliance with Trial Medicine | 1 | 0 | 0 | 1 |
| Overall Study | Other | 1 | 5 | 2 | 0 |
| Overall Study | Protocol Violation | 3 | 0 | 0 | 0 |
| Overall Study | Serious Adverse Event | 0 | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Xyrem Placebo + Modafinil Placebo | Xyrem + Modafinil Placebo | Xyrem Placebo + Modafinil at Established Dose | Xyrem + Modafinil at Established Dose | Total |
|---|---|---|---|---|---|
| Age Continuous | 41.0 years STANDARD_DEVIATION 13.35 | 35.1 years STANDARD_DEVIATION 12.86 | 38.9 years STANDARD_DEVIATION 15.62 | 38.9 years STANDARD_DEVIATION 15.87 | 38.6 years STANDARD_DEVIATION 14.6 |
| Race/Ethnicity, Customized Asian | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Black | 11 Participants | 2 Participants | 5 Participants | 3 Participants | 21 Participants |
| Race/Ethnicity, Customized Caucasian | 43 Participants | 47 Participants | 57 Participants | 48 Participants | 195 Participants |
| Race/Ethnicity, Customized Hispanic | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 3 Participants |
| Sex: Female, Male Female | 31 Participants | 24 Participants | 31 Participants | 29 Participants | 115 Participants |
| Sex: Female, Male Male | 24 Participants | 26 Participants | 32 Participants | 25 Participants | 107 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 39 / 56 | 33 / 55 | 34 / 63 | 45 / 57 |
| serious Total, serious adverse events | 2 / 56 | 0 / 55 | 1 / 63 | 1 / 57 |
Outcome results
Primary
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.
Time frame: Baseline to Week 8
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Xyrem Placebo + Modafinil Placebo | Daytime Sleep Latency as Measured by the Maintenance of Wakefulness Test (MWT) | -2.72 Minutes | Standard Deviation 4.535 |
| Xyrem + Modafinil Placebo | Daytime Sleep Latency as Measured by the Maintenance of Wakefulness Test (MWT) | 0.58 Minutes | Standard Deviation 5.675 |
| Xyrem Placebo + Modafinil at Established Dose | Daytime Sleep Latency as Measured by the Maintenance of Wakefulness Test (MWT) | -0.53 Minutes | Standard Deviation 4.358 |
| Xyrem + Modafinil at Established Dose | Daytime Sleep Latency as Measured by the Maintenance of Wakefulness Test (MWT) | 2.68 Minutes | Standard Deviation 5.071 |
p-value: <0.001Dunnett's
p-value: <0.001Dunnett's