The average sleep latencies (in minutes) on the MWT at baseline for the 2 controlled trials are shown in Table 1 below, along with the average change from baseline on the MWT at final visit.

The percentages of patients who showed any degree of improvement on the CGI-C in the two clinical trials are shown in Table 2 below.

Similar statistically significant treatment-related improvements were seen on other measures of impairment in narcolepsy, including a patient assessed level of daytime sleepiness on the ESS (p< 0.001 for each dose in comparison to placebo).

Nighttime sleep measured with polysomnography was not affected by the use of PROVIGIL.

Obstructive Sleep Apnea/Hypopnea Syndrome (OSAHS)

The effectiveness of PROVIGIL in reducing the excessive sleepiness associated with OSAHS was established in two clinical trials. In both studies, patients were enrolled who met the International Classification of Sleep Disorders (ICSD) criteria for OSAHS (which are also consistent with the American Psychiatric Association DSM-IV criteria). These criteria include either, 1) excessive sleepiness or insomnia, plus frequent episodes of impaired breathing during sleep, and associated features such as loud snoring, morning headaches and dry mouth upon awakening; or 2) excessive sleepiness or insomnia and polysomnography demonstrating one of the following: more than five obstructive apneas, each greater than 10 seconds in duration, per hour of sleep and one or more of the following: frequent arousals from sleep associated with the apneas, bradytachycardia, and arterial oxygen desaturation in association with the apneas. In addition, for entry into these studies, all patients were required to have excessive sleepiness as demonstrated by a score ≥ 10 on the Epworth Sleepiness Scale, despite treatment with continuous positive airway pressure (CPAP). Evidence that CPAP was effective in reducing episodes of apnea/hypopnea was required along with documentation of CPAP use.

In the first study, a 12-week multicenter placebo-controlled trial, a total of 327 patients were randomized to receive PROVIGIL 200 mg/day, PROVIGIL 400 mg/day, or matching placebo. The majority of patients (80%) were fully compliant with CPAP, defined as CPAP use > 4 hours/night on > 70% nights. The remainder were partially CPAP compliant, defined as CPAP use < 4 hours/night on > 30% nights. CPAP use continued throughout the study. The primary measures of effectiveness were 1) sleep latency, as assessed by the Maintenance of Wakefulness Test (MWT) and 2) the change in the patient's overall disease status, as measured by the Clinical Global Impression of Change (CGI-C) at week 12 or the final visit. (See CLINICAL TRIALS, Narcolepsy section above for a description of these tests.)

Patients treated with PROVIGIL showed a statistically significant improvement in the ability to remain awake compared to placebo-treated patients as measured by the MWT (p< 0.001) at endpoint [Table 1]. PROVIGIL-treated patients also showed a statistically significant improvement in clinical condition as rated by the CGI-C scale (p< 0.001) [Table 2]. The two doses of PROVIGIL performed similarly.

In the second study, a 4-week multicenter placebo-controlled trial, 157 patients were randomized to either PROVIGIL 400 mg/day or placebo. Documentation of regular CPAP use (at least 4 hours/night on 70% of nights) was required for all patients. The primary outcome measure was the change from baseline on the ESS at week 4 or final visit. The baseline ESS scores for the PROVIGIL and placebo groups were 14.2 and 14.4, respectively. At week 4, the ESS was reduced by 4.6 in the PROVIGIL group and by 2.0 in the placebo group, a difference that was statistically significant (p< 0.0001).

Nighttime sleep measured with polysomnography was not affected by the use of PROVIGIL.

Shift Work Sleep Disorder (SWSD)

The effectiveness of PROVIGIL for the excessive sleepiness associated with SWSD was demonstrated in a 12-week placebo-controlled clinical trial. A total of 209 patients with chronic SWSD were randomized to receive PROVIGIL 200 mg/day or placebo. All patients met the International Classification of Sleep Disorders (ICSD-10) criteria for chronic SWSD (which are consistent with the American Psychiatric Association DSM-IV criteria for Circadian Rhythm Sleep Disorder: Shift Work Type). These criteria include 1) either: a) a primary complaint of excessive sleepiness or insomnia which is temporally associated with a work period (usually night work) that occurs during the habitual sleep phase, or b) polysomnography and the MSLT demonstrate loss of a normal sleep-wake pattern (i.e., disturbed chronobiological rhythmicity); and 2) no other medical or mental disorder accounts for the symptoms, and 3) the symptoms do not meet criteria for any other sleep disorder producing insomnia or excessive sleepiness (e.g., time zone change [jet lag] syndrome).

Bookmark this page: