Narcolepsy
Conditions
Keywords
Narcolepsy, Excessive Sleepiness, Cataplexy, Sleep Attacks, Excessive Sleepiness associated with Narcolepsy, Cephalon, Cephalon, Inc, Nuvigil
Brief summary
The primary objective of this study is to determine whether treatment with Armodafinil (CEP-10953) is more effective than placebo treatment for patients with excessive sleepiness associated with narcolepsy by measuring mean sleep latency from the Maintenance of Wakefulness Test (MWT) (20-minute version)(average of 4 naps at 0900, 1100, 1300, and 1500) and by the Clinical Global Impressions of Change (CGI-C) ratings (as related to general condition) at week 12 (or last postbaseline observation)
Interventions
DRUGArmodafinil
Armodafinil 250 mg once daily in the morning
DRUGPlacebo
Matching placebo tablets once daily
Sponsors
Cephalon
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Diagnosis and Criteria for Inclusion: Patients are included in the study if all of the following criteria are met: * Written informed consent is obtained * The patient is an outpatient, man or woman of any ethnic origin, 18 to 65 years of age (inclusive) * The patient has a complaint of excessive sleepiness * The patient has a current diagnosis of narcolepsy according to ICSD criteria. * The patient is in good health as determined by a medical and psychiatric history, physical examination, electrocardiogram (ECG), and serum chemistry, hematology, and urinalysis. * Women must be surgically sterile, 2 years postmenopausal, or, if of child-bearing potential, using a medically accepted method of birth control (ie, barrier method with spermicide, steroidal contraceptive \[oral, implanted, and Depo-Provera contraceptives must be used in conjunction with a barrier method\], or intrauterine device \[IUD\]) and agree to continued use of this method for the duration of the study. * The patient has a mean sleep latency of 6 minutes or less as determined by the Multiple Sleep Latency Test (MSLT) (performed at 0900, 1100, 1300, and 1500). * The patient has a CGI-S (Clinical Global Impression of Severity of Illness) rating of 4 or more. * The patient does not have any medical or psychiatric disorders that could account for the excessive daytime sleepiness. * The patient is able to complete self rating scales and computer-based testing. * The patient is willing and able to comply with study restrictions and to attend regularly scheduled clinic visits as specified in this protocol. Criteria for Exclusion: Patients are excluded from participating in this study if 1 or more of the following criteria are met. The patient: * has any clinically significant, uncontrolled medical or psychiatric conditions (treated or untreated) * has a probable diagnosis of a current sleep disorder other than narcolepsy * consumed caffeine including coffee, tea and/or other caffeine containing beverages or food averaging more than 600 mg of caffeine per day * used any prescription drugs disallowed by the protocol or clinically significant use of over the-counter (OTC) drugs within 7 days before the second screening visit * has a history of alcohol, narcotic, or any other drug abuse as defined by the Diagnostic and Statistical Manual of Mental Disorders of the American Psychiatric Association, 4th Edition (DSM IV) * has a positive UDS at the screening visit, without medical explanation * 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 used an investigational drug within 1 month before the screening visit * has any disorder that may interfere with drug absorption, distribution, metabolism, or excretion (including gastrointestinal surgery) * has a known clinically significant drug sensitivity to stimulants or modafinil
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Maintenance of Wakefullness Test (MWT) Score at 12 Weeks | change from baseline at 12 weeks | The Maintenance of Wakefulness Test (MWT) is an objective assessment of sleepiness that measures the ability of a subject to remain awake. Long latencies to sleep are indicative of a patient's ability to remain awake. The change from baseline in the mean sleep latency from the MWT (average of 4 tests at 0900, 1100, 1300, and 1500) was analyzed at weeks 4, 8, and 12. The primary efficacy variable was the mean change from the baseline assessment in MWT sleep latency as assessed at week 12 (or last post-baseline visit). |
| Change From Baseline in Clinical Global Impression of Change (CGI-C) Score at 12 Weeks | change from baseline at 12 weeks | Number of participants who had at least minimal improvement in CGI-C ratings at Week 12 or last post-baseline visit. The CGI-C uses the following categories and scoring assignments: 1=Very much improved; 2=Much improved; 3=Minimally improved; 4=No change; 5=Minimally worse; 6=Much worse; and 7=Very much worse. Severity of illness was assessed at baseline by the CGI-S, which consists of the following categories: 1=Normal (shows no signs of illness); 2=Borderline ill; 3=Mildly (Slightly) ill; 4=Moderately ill; 5=Markedly ill; 6=Severely ill; and 7=Among the most extremely ill patients. |
Participant flow
Recruitment details
47 centers in the US, Canada, France, Germany, Russia, and Australia. First patient enrolled (treatment): 23 March 2004/ Last patient last visit: 10 January 2005
Pre-assignment details
2 female patients withdrew after randomization but prior to receiving study drug (1 withdrew consent and 1 was lost to follow-up)
Participants by arm
| Arm | Count |
|---|---|
| Armodafinil 250 mg/Day Armodafinil 250 mg once daily in the morning | 67 |
| Armodafinil 150 mg/Day Armodafinil 150 mg once daily in the morning | 65 |
| Placebo Matching placebo tablets once daily in the morning | 64 |
| Total | 196 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 5 | 1 |
| Overall Study | Lack of Efficacy | 2 | 0 | 2 |
| Overall Study | Lost to Follow-up | 0 | 1 | 1 |
| Overall Study | Miscellaneous | 2 | 6 | 1 |
| Overall Study | Physician Decision | 2 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 4 | 4 |
Baseline characteristics
| Characteristic | Placebo | Armodafinil 250 mg/Day | Armodafinil 150 mg/Day | Total |
|---|---|---|---|---|
| Age Categorical <=18 years | 0 participants | 0 participants | 0 participants | 0 participants |
| Age Categorical >=65 years | 0 participants | 1 participants | 0 participants | 1 participants |
| Age Categorical Between 18 and 65 years | 63 participants | 66 participants | 64 participants | 193 participants |
| Age Continuous | 39.2 years STANDARD_DEVIATION 11.98 | 35.0 years STANDARD_DEVIATION 12.52 | 40.4 years STANDARD_DEVIATION 12.52 | 38.1 years STANDARD_DEVIATION 12.5 |
| Gender Female | 31 participants | 42 participants | 36 participants | 109 participants |
| Gender Male | 32 participants | 25 participants | 28 participants | 85 participants |
| Region of Enrollment Australia | 4 participants | 5 participants | 5 participants | 14 participants |
| Region of Enrollment Canada | 12 participants | 12 participants | 12 participants | 36 participants |
| Region of Enrollment France | 3 participants | 3 participants | 3 participants | 9 participants |
| Region of Enrollment Germany | 4 participants | 5 participants | 4 participants | 13 participants |
| Region of Enrollment Russian Federation | 4 participants | 5 participants | 4 participants | 13 participants |
| Region of Enrollment United States | 37 participants | 37 participants | 37 participants | 111 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 29 / 67 | 21 / 64 | 11 / 63 |
| serious Total, serious adverse events | 0 / 67 | 1 / 64 | 0 / 63 |
Outcome results
Primary
Change From Baseline in Clinical Global Impression of Change (CGI-C) Score at 12 Weeks
Number of participants who had at least minimal improvement in CGI-C ratings at Week 12 or last post-baseline visit. The CGI-C uses the following categories and scoring assignments: 1=Very much improved; 2=Much improved; 3=Minimally improved; 4=No change; 5=Minimally worse; 6=Much worse; and 7=Very much worse. Severity of illness was assessed at baseline by the CGI-S, which consists of the following categories: 1=Normal (shows no signs of illness); 2=Borderline ill; 3=Mildly (Slightly) ill; 4=Moderately ill; 5=Markedly ill; 6=Severely ill; and 7=Among the most extremely ill patients.
Time frame: change from baseline at 12 weeks
Population: Safety Analysis set of 194 total patients (received at least 1 dose of study drug): 2 patients withdrew after randomization but prior to receiving study drug (1 withdrew consent and 1 was lost to follow-up).~Full Analysis set of 176 total patients: 18 patients that had withdrawn from the study were non-evaluable for efficacy analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Armodafinil 250 mg/Day | Change From Baseline in Clinical Global Impression of Change (CGI-C) Score at 12 Weeks | 60 Participants |
| Armodafinil 150 mg/Day | Change From Baseline in Clinical Global Impression of Change (CGI-C) Score at 12 Weeks | 58 Participants |
| Placebo | Change From Baseline in Clinical Global Impression of Change (CGI-C) Score at 12 Weeks | 58 Participants |
| Armodafinil Combined Group (250 mg/Day and 150 mg/Day) | Change From Baseline in Clinical Global Impression of Change (CGI-C) Score at 12 Weeks | 118 Participants |
p-value: <0.0001Cochran-Mantel-Haenszel
Primary
Change From Baseline in Maintenance of Wakefullness Test (MWT) Score at 12 Weeks
The Maintenance of Wakefulness Test (MWT) is an objective assessment of sleepiness that measures the ability of a subject to remain awake. Long latencies to sleep are indicative of a patient's ability to remain awake. The change from baseline in the mean sleep latency from the MWT (average of 4 tests at 0900, 1100, 1300, and 1500) was analyzed at weeks 4, 8, and 12. The primary efficacy variable was the mean change from the baseline assessment in MWT sleep latency as assessed at week 12 (or last post-baseline visit).
Time frame: change from baseline at 12 weeks
Population: Safety Analysis set of 194 total patients: 2 patients withdrew after randomization but prior to receiving study drug (1 withdrew consent and 1 was lost to follow-up).~Full Analysis set of 176 total patients: 18 patients that had withdrawn from the study were non-evaluable for efficacy.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Armodafinil 250 mg/Day | Change From Baseline in Maintenance of Wakefullness Test (MWT) Score at 12 Weeks | 2.6 Minutes | Standard Deviation 6.24 |
| Armodafinil 150 mg/Day | Change From Baseline in Maintenance of Wakefullness Test (MWT) Score at 12 Weeks | 1.3 Minutes | Standard Deviation 6.31 |
| Placebo | Change From Baseline in Maintenance of Wakefullness Test (MWT) Score at 12 Weeks | -1.9 Minutes | Standard Deviation 6.87 |
| Armodafinil Combined Group (250 mg/Day and 150 mg/Day) | Change From Baseline in Maintenance of Wakefullness Test (MWT) Score at 12 Weeks | 1.9 Minutes | Standard Deviation 6.28 |
Comparison: Statistical data is for the Armodafinil Combined treatment (250 mg/day and 150 mg/day groups) compared to the placebo treatment groupp-value: 0.002495% CI: [1.02, 4.61]ANCOVA