Chronic Shift Work Sleep Disorder
Conditions
Brief summary
The purpose of the study is to compare the overnight efficacy and plasma concentration-time profiles of armodafinil and PROVIGIL, after multiple doses, in patients with excessive sleepiness associated with chronic Shift Work Sleep Disorder (SWSD).
Detailed description
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study of the Efficacy and Multiple-Dose Plasma Concentration-Time Profiles of Armodafinil and PROVIGIL in Patients with Chronic Shift Work Sleep Disorder
Interventions
DRUGPROVIGIL 200 mg
PROVIGIL 200 mg/day
Armodafinil 250 mg/day
DRUGArmodafinil 200 mg
Armodafinil 200 mg/day
Armodafinil 150 mg/day
DRUGPlacebo
Matching placebo tablets
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
Patients are included in the study if all of the following criteria are met: * The patient speaks and writes in English. * The patient is a man or woman of any ethnic origin aged 18 through 65 years. * The patient is in good health as determined by a medical and psychiatric history, medical examination, serum chemistry, and hematology. * The patient has a diagnosis of SWSD according to the International Classification of Sleep Disorders (ICSD) criteria, and must have had excessive sleepiness during night shifts for at least 3 months. * The patient must be planning to work at least 3 to 5 nights (per week), of which at least 3 nights will be consecutive. * The patient must work night shifts that include at least 6 hours between 2200 and 0800 (+30 minutes) and be no longer than 12 hours (+30 minutes) in duration. * The patient has a mean sleep latency of 6 minutes or less as determined by the MSLT (average of naps at 0100, 0300, 0500, and 0700). * The patient has a Clinical Global Impression of Severity of Illness (CGI-S) rating of 4 or more as it pertains to sleepiness during night shifts including the commute from work. * Women of childbearing potential (not surgically sterile or 2 years postmenopausal) must use a medically accepted method of contraception and must agree to continue use of this method for the duration of the study and for 30 days after participation in the study. Acceptable methods of contraception include abstinence, barrier method with spermicide, steroidal contraceptive (oral, transdermal, implanted and injected) in conjunction with a barrier method, and intrauterine device (IUD). * The patient is willing to comply with study restrictions and remain at the clinic overnight as required. * The patient may have been prescribed PROVIGIL or stimulant therapy for their sleep disorder; however, they must have undergone a washout period of at least 7 days prior to screening assessments done at the second screening visit.
Exclusion criteria
Patients are excluded from participating in this study if 1 or more of the following criteria are met: * The patient has any clinically significant medical or psychiatric conditions (treated or untreated). * The patient has a probable diagnosis of a current sleep disorder other than SWSD. * The patient consumes caffeine including coffee, tea, and/or other caffeine-containing beverages or foods averaging more than 600 mg of caffeine/day within 2 weeks of the start of study drug administration. * The patient has medically unexplainable positive urine drug screen (UDS) result at the screening visit. * The patient has clinically significant deviation from normal in clinical laboratory results, vital signs, or physical examination. * The patient has received any investigational drug within 30 days or 5 half-lives (whichever is longer) before study drug administration, or in the case of a new chemical entity, 3 months or 5 half-lives (whichever is longer) before study drug adminstration. * The patient used any prescription drugs disallowed by the protocol or clinical significant use of over-the-counter (OTC) drugs within 7 days before the second screening/baseline visit. * The patient has any disorder (including gastrointestinal surgery) that may interfere with drug absorption, distribution, metabolism, or excretion. * The patient has known or suspected hypersensitivity to stimulants and/or modafinil or any ingredient present in the study drug. * The patient has a history (within the past 5 years) of alcohol, narcotic, or any other drug abuse as defined by the Diagnostic and Statistical Manual or Mental Disorders of the American Psychiatric Association, Fourth Edition, Text Revision (DSM-IV-TR). * The patient is a pregnant or lactating woman. * The patient has donated, within 56 days prior to study drug administration, any blood or plasma in excess of 450 mL.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Multiple Sleep Latency Test (MSLT) | Endpoint (Visit 4) change from baseline (Visit 2) | The Multiple Sleep Latency Test (MSLT) is an objective assessment of sleepiness that measures the likelihood of falling asleep. Five 20-minute (maximum) MSLT naps were performed (at 2300, 0100, 0300, 0500, and 0700) at both the screening/baseline assessment visit (Visit 2) and at endpoint (Visit 4). Each nap was terminated after 20 minutes if no sleep occurred. Sleep latency was measured as the elapsed time from lights out to the first epoch scored as sleep. |
| Psychomotor Vigilance Task (PVT) | Endpoint (Visit 4) change from baseline (Visit 2) | The computer-based PVT took 10 minutes to complete and measured reaction time stimulus in milliseconds. The reaction time consisted of the digits 000 initially appearing in a window on the PVT device, after which the 3-digit numbers increased in milliseconds until the response button was pressed by the patient. The resulting number at the button press was the reaction time in milliseconds. There was a variable 1- to 10-second interstimulus interval. After pressing the button in response to each stimulus, the button was released and the patient awaited the next stimulus. |
Countries
United States
Participant flow
Recruitment details
16 centers in the US. First participant enrolled: 7 September 2005/ Last participant last visit: 1 December 2005
Pre-assignment details
2 male participants withdrew after randomization but prior to receiving study drug (1 for noncompliance and 1 at the request of the sponsor)
Participants by arm
| Arm | Count |
|---|---|
| PROVIGIL 200 mg/Day PROVIGIL 200 mg once daily only on nights worked | 29 |
| Armodafinil 250 mg/Day Armodafinil 250 mg once daily only on nights worked | 28 |
| Armodafinil 200 mg/Day Armodafinil 200 mg once daily only on nights worked | 27 |
| Armodafinil 150 mg/Day Armodafinil 150 mg once daily only on nights worked | 25 |
| Placebo Matching placebo tablets once daily only on nights worked | 27 |
| Total | 136 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 3 | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Miscellaneous | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Physician Decision | 1 | 0 | 1 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | PROVIGIL 200 mg/Day | Armodafinil 250 mg/Day | Armodafinil 200 mg/Day | Armodafinil 150 mg/Day | Placebo | Total |
|---|---|---|---|---|---|---|
| Age Categorical <=18 years | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Age Categorical >=65 years | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Age Categorical Between 18 and 65 years | 29 participants | 28 participants | 26 participants | 25 participants | 26 participants | 134 participants |
| Age Continuous | 36.8 years STANDARD_DEVIATION 8.92 | 34.3 years STANDARD_DEVIATION 9.87 | 34.5 years STANDARD_DEVIATION 7.6 | 38.3 years STANDARD_DEVIATION 12.83 | 38.0 years STANDARD_DEVIATION 9.83 | 36.3 years STANDARD_DEVIATION 9.9 |
| Gender Female | 18 participants | 12 participants | 13 participants | 8 participants | 6 participants | 57 participants |
| Gender Male | 11 participants | 16 participants | 13 participants | 17 participants | 20 participants | 77 participants |
| Region of Enrollment United States | 29 participants | 28 participants | 26 participants | 25 participants | 26 participants | 134 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 29 | 8 / 28 | 9 / 26 | 4 / 25 | 3 / 26 |
| serious Total, serious adverse events | 0 / 29 | 0 / 28 | 0 / 26 | 0 / 25 | 0 / 26 |
Outcome results
Primary
Multiple Sleep Latency Test (MSLT)
The Multiple Sleep Latency Test (MSLT) is an objective assessment of sleepiness that measures the likelihood of falling asleep. Five 20-minute (maximum) MSLT naps were performed (at 2300, 0100, 0300, 0500, and 0700) at both the screening/baseline assessment visit (Visit 2) and at endpoint (Visit 4). Each nap was terminated after 20 minutes if no sleep occurred. Sleep latency was measured as the elapsed time from lights out to the first epoch scored as sleep.
Time frame: Endpoint (Visit 4) change from baseline (Visit 2)
Population: * 1 Placebo Patient did not have an MSLT but did complete the other Primary Measure (PVT) and other requirements. This patient was termed a Completer.~* 1 Patient in the Armodafinil 200 mg/day group had an MSLT performed but then discontinued the study drug before reaching the study endpoint and was termed a Non-Completer for the Study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PROVIGIL 200 mg/Day | Multiple Sleep Latency Test (MSLT) | 2.0 Minutes | Standard Deviation 3.05 |
| Armodafinil 250 mg/Day | Multiple Sleep Latency Test (MSLT) | 3.7 Minutes | Standard Deviation 4.33 |
| Armodafinil 200 mg/Day | Multiple Sleep Latency Test (MSLT) | 3.7 Minutes | Standard Deviation 5.07 |
| Armodafinil 150 mg/Day | Multiple Sleep Latency Test (MSLT) | 2.7 Minutes | Standard Deviation 4.24 |
| Placebo | Multiple Sleep Latency Test (MSLT) | 1.1 Minutes | Standard Deviation 3.76 |
Comparison: Sample size requirements were not based on statistical considerations. The null hypothesis was Ho: μplacebo = μ150 = μ200 = μ250 = μprovigil versus Ha: at least 2 of the means are different, where μ represented the change from baseline to the endpoint.p-value: 0.1236ANCOVA
Primary
Psychomotor Vigilance Task (PVT)
The computer-based PVT took 10 minutes to complete and measured reaction time stimulus in milliseconds. The reaction time consisted of the digits 000 initially appearing in a window on the PVT device, after which the 3-digit numbers increased in milliseconds until the response button was pressed by the patient. The resulting number at the button press was the reaction time in milliseconds. There was a variable 1- to 10-second interstimulus interval. After pressing the button in response to each stimulus, the button was released and the patient awaited the next stimulus.
Time frame: Endpoint (Visit 4) change from baseline (Visit 2)
Population: Of the patients who completed the study, 1 patient in the PROVIGIL 200 mg/day treatment group and 1 patient in the Armodafinil 150 mg/day treatment group did not complete their PVT assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PROVIGIL 200 mg/Day | Psychomotor Vigilance Task (PVT) | -16.5 Milliseconds | Standard Deviation 27.58 |
| Armodafinil 250 mg/Day | Psychomotor Vigilance Task (PVT) | -29.8 Milliseconds | Standard Deviation 38.35 |
| Armodafinil 200 mg/Day | Psychomotor Vigilance Task (PVT) | -37.4 Milliseconds | Standard Deviation 63.16 |
| Armodafinil 150 mg/Day | Psychomotor Vigilance Task (PVT) | -33.1 Milliseconds | Standard Deviation 44.52 |
| Placebo | Psychomotor Vigilance Task (PVT) | 2.4 Milliseconds | Standard Deviation 34.52 |
Comparison: Sample size requirements were not based on statistical considerations. The null hypothesis was Ho: μplacebo = μ150 = μ200 = μ250 = μprovigil versus Ha: at least 2 of the means are different, where μ represented the change from baseline to the endpoint .p-value: 0.0945ANCOVA