NUVIGIL improves wakefulness throughout the day in patients with excessive sleepiness associated with treated OSA, SWD, and narcolepsy1

NUVIGIL has been studied in 4 pivotal trials.1

  • Studied in 1108 patients1–4
    • In four 12-week, double-blind, randomized, placebo-controlled trials
    • In patients with treated obstructive sleep apnea (OSA), shift work disorder (SWD), and narcolepsy

Primary efficacy measures

The primary efficacy measures in the pivotal trials for NUVIGIL were the Maintenance of Wakefulness Test (MWT) or Multiple Sleep Latency Test (MSLT), and the Clinical Global Impression of Change (CGI-C).2–4

MWT3,5

An objective physiologic assessment of sleepiness that measures a subject's ability to sustain wakefulness.

  • In the OSA and narcolepsy studies, a coprimary endpoint was the average of 4 MWT sessions from 9 am to 3 pm
  • In the clinical studies of NUVIGIL, patients were instructed to try to remain awake in a darkened room while in a semireclined position during a series of 30-minute (for the OSA studies) or 20-minute (for the narcolepsy study) periods at scheduled times
  • Sleep latency was defined as the time to onset of the first of 3 consecutive epochs of:
    • Stage 1 sleep
    • The time to onset of any epoch of stage 2, 3, 4 sleep
    • REM sleep
  • Epochs were individually scored using the 50% (or 16-second) rule
    • If patients fell asleep, they were awakened immediately but were required to stay in bed, and they were prevented from falling asleep again for the remainder of the test session

MSLT3,5

An objective assessment of sleepiness that measures the likelihood of falling asleep.

  • In the SWD study, a coprimary endpoint was the average of 4 MSLT sessions from 2 am to 8 am
  • In the clinical study for NUVIGIL conducted in patients with SWD, five 20-minute (maximum) MSLT naps were performed at scheduled 2-hour intervals
  • The patient was instructed to lie quietly and attempt to sleep. Each MSLT nap continued until:
    • 3 consecutive 30-second epochs of stage 1 sleep were reached or
    • Any single 30-second epoch of stage 2, 3, 4, or REM sleep was reached
  • Sleep latency was defined as the elapsed time from lights-out to the first epoch scored as sleep. With a 30-second scoring epoch, this criterion was reached when sleep occupied at least 16 seconds of any epoch. Each nap was terminated after 20 minutes if no sleep occurred. If patients fell asleep, they were awakened and kept awake while remaining in bed

CGI-C

A standard assessment tool used to measure the impact of symptoms or disease on a patient’s overall clinical condition, as well as changes in response to treatment. Change in overall condition is assessed using the CGI-C, a 7-point scale that ranges from Very Much Improved to Very Much Worse.

Secondary efficacy measures

Efficacy as measured by the Epworth Sleepiness Scale (ESS) or the Karolinska Sleep Scale (KSS) was a secondary endpoint in the pivotal trials for NUVIGIL.2–4

ESS6,7

A validated self-report scale for measurement of sleep propensity in various situations of daily living. Patients rate their chance of dozing off or falling asleep in 8 different situations (eg, sitting and reading, talking to someone, or being stopped in traffic).

Scores from the 8 situations are added to yield a final score ranging from 0 to 24. Scores ≥10 are generally defined as pathologic levels of sleepiness.

KSS8

A validated self-report instrument used to measure the level of sleepiness on a 9-point scale ranging from 1=very alert to 9=very sleepy, great effort to stay awake, fighting sleep.

References: 1. NUVIGIL [package insert]. Frazer, PA: Cephalon, Inc; 2008. 2. Roth T, White D, Schmidt-Nowara W, et al. Effects of armodafinil in the treatment of residual excessive sleepiness associated with obstructive sleep apnea/hypopnea syndrome: a 12-week, multicenter, double-blind, randomized, placebo-controlled study in nCPAP-adherent adults. Clin Ther. 2006;28(5):689-706. 3. Data on file. Cephalon, Inc. 4. Harsh JR, Hayduk R, Rosenberg R, et al. The efficacy and safety of armodafinil as treatment for adults with excessive sleepiness associated with narcolepsy. Curr Med Res Opin. 2006;22(4):761-774. 5. Littner MR, Kushida C, Wise M, et al. Practice parameters for clinical use of the Multiple Sleep Latency Test and the Maintenance of Wakefulness Test. Sleep. 2005;28(1):113-121. 6. Johns MW. Reliability and factor analysis of the Epworth Sleepiness Scale. Sleep. 1992;15(4):376-381. 7. Johns MW. A new method for measuring daytime sleepiness: the Epworth Sleepiness Scale. Sleep. 1991;14(6):540-545. 8. Akerstedt T, Gillberg M. Subjective and objective sleepiness in the active individual. Int J Neurosci. 1990;52(1-2):29-37.

Please see Important Safety Information below and full prescribing information for NUVIGIL.

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Important Information for Physicians


Indications

NUVIGIL is indicated to improve wakefulness in patients with excessive sleepiness associated with obstructive sleep apnea/hypopnea syndrome (OSA), shift work sleep disorder and narcolepsy.

In OSA, NUVIGIL is indicated as an adjunct to standard treatment(s) for the underlying obstruction. If continuous positive airway pressure (CPAP) is the treatment of choice, the encouragement of and periodic assessment of CPAP compliance is necessary and a maximal effort to treat with CPAP for an adequate period of time should be made prior to initiating NUVIGIL. Careful attention to the diagnosis and treatment of the underlying sleep disorder(s) is important. Prescribers should be aware that some patients may have more than one sleep disorder contributing to their excessive sleepiness.

Important Safety Information

Warnings

Serious rash requiring hospitalization and discontinuation of treatment has been reported in adults in association with the use of armodafinil and in adults and children in association with use of modafinil, a racemic mixture of S and R modafinil (the latter is armodafinil, the active ingredient in NUVIGIL).

No serious skin rashes have been reported in adult clinical trials (0 per 1,595) of armodafinil. However, cases of serious rash have been reported in adults in postmarketing experience. Because armodafinil is the R isomer of modafinil, a similar risk of serious rash in pediatric patients with armodafinil cannot be ruled out.

In clinical trials of modafinil, the incidence of rash resulting in discontinuation was approximately 0.8% (13 per 1,585) in pediatric patients; these rashes included 1 case of possible Stevens-Johnson Syndrome (SJS) and 1 case of apparent multi-organ hypersensitivity reaction. Several of the cases were associated with fever and other abnormalities (e.g., vomiting, leukopenia). No serious skin rashes have been reported in adult clinical trials of modafinil. Rare cases of serious or life-threatening rash, including SJS, Toxic Epidermal Necrolysis (TEN) and Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) have been reported in adults and children in postmarketing experience with modafinil.

Although benign rashes occur with NUVIGIL, it is not possible to reliably predict which rashes will prove to be serious. NUVIGIL should ordinarily be discontinued at the first sign of rash unless the rash is clearly not drug-related.

NUVIGIL has not been studied in pediatric patients in any setting and is not approved for use in pediatric patients for any indication.

One serious case of angioedema and one case of hypersensitivity (with rash, dysphagia, and bronchospasm) were observed among patients treated with NUVIGIL. Patients should be advised to discontinue therapy and immediately report to their physician any signs or symptoms suggesting angioedema or anaphylaxis.

Multi-organ hypersensitivity reactions, including at least 1 fatality postmarketing, have occurred in close temporal association to the initiation of modafinil. If a multi-organ hypersensitivity reaction is suspected, NUVIGIL should be discontinued.

Patients should be advised that their level of wakefulness may not return to normal. Patients should be frequently reassessed for their degree of sleepiness and, if appropriate, advised to avoid driving or any other potentially dangerous activity.

Psychiatric adverse experiences have been reported in patients treated with modafinil. Postmarketing adverse events associated with the use of modafinil have included mania, delusions, hallucinations, suicidal ideation and aggression, some resulting in hospitalization. In controlled trials in adults administered NUVIGIL, psychiatric symptoms resulting in treatment discontinuation were anxiety, agitation, nervousness, and irritability. Caution should be exercised when NUVIGIL is given to patients with a history of psychosis, depression, or mania. Consider discontinuing NUVIGIL if psychiatric symptoms develop.

Precautions

  • Although NUVIGIL has not been shown to produce functional impairment, any drug affecting the CNS may alter judgment, thinking or motor skills. Patients should be cautioned about operating an automobile or other hazardous machinery until reasonably certain that NUVIGIL therapy will not adversely affect their ability to engage in such activities.
  • Patients with a recent history of myocardial infarction or unstable angina should be treated with caution. NUVIGIL should not be used in patients with a history of left ventricular hypertrophy or in patients with mitral valve prolapse who have experienced mitral valve prolapse syndrome when previously receiving CNS stimulants. There were also a greater proportion of patients on NUVIGIL requiring new or increased use of antihypertensive medications compared to patients on placebo. Increased monitoring of blood pressure may be appropriate in patients on NUVIGIL.
  • NUVIGIL may interact with drugs that inhibit, induce, or are metabolized by cytochrome P450 isoenzymes.
  • The effectiveness of steroidal contraceptives may be reduced when used with NUVIGIL and for one month after discontinuation of therapy.
  • The concomitant use of NUVIGIL and alcohol has not been studied and should be avoided.

Common Adverse Reactions

In clinical trials, the most commonly reported adverse events (≥5%) were headache, nausea, dizziness, and insomnia. Most adverse experiences were rated as mild to moderate.

Drug Abuse and Dependence

NUVIGIL is a Schedule IV drug. Although the abuse potential of NUVIGIL has not been studied, its abuse potential is likely to be similar to that of modafinil. Modafinil produces psychoactive and euphoric effects, alterations in mood, perception, thinking and feelings typical of other CNS stimulants. Physicians should follow patients closely, especially those with a history of drug and/or stimulant abuse.

Please see full prescribing information for NUVIGIL.

If you are a patient, CLICK HERE