Armodafinil (CEP-10953) in Treatment of Excessive Sleepiness Associated With Obstructive Sleep Apnea/Hypopnea Syndrome(OSAHS)
Condition: Obstructive Sleep Apnea; Hypopnea
MeSH terms: Apnea; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Sleepiness
Intervention: Armodafinil 250 mg/day; Armodafinil 150 mg/day; Placebo
Intervention description: Armodafinil 250 mg once daily in the morning; Armodafinil 150 mg once daily in the morning; Matching placebo tablets once daily in the morning
Intervention MeSH terms: Modafinil
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Enrollment: 395.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Excessive Sleepiness; Obstructive Sleep Apnea; Obstructive Sleep Hypopnea; nCPAP; Cephalon; Cephalon, Inc; NUVIGIL

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 obstructive sleep apnea/hypopnea syndrome (OSAHS) by measuring mean sleep
      latency from the Maintenance of Wakefulness Test (MWT) (30-minute version) (average of 4 naps
      at 0900, 1100, 1300, and 1500) and by Clinical Global Impression of Change (CGI-C) ratings
      (as related to general condition) at week 12, or last post-baseline visit.
    

Eligibility criteria:

        Inclusion Criteria:

        Patients are included in the study if all of the following criteria are met:

          1. Written informed consent is obtained.

          2. The patient is an outpatient, man or woman of any ethnic origin, 18 to 65 years of age
             (inclusive).

          3. The patient has a complaint of excessive sleepiness despite nCPAP therapy being
             effective and being a regular user of nCPAP therapy.

          4. The patient has a current diagnosis of OSAHS according to International Classification
             of Sleep Disorders (ICSD) criteria.

          5. The patient meets the following nCPAP therapy requirements:

               -  Adequate education and intervention efforts to encourage nCPAP therapy use must
                  be documented.

               -  A patient's nCPAP therapy regimen must be stable for at least 4 weeks.

               -  nCPAP therapy is shown to be effective, with effectiveness defined as having an
                  apnea-hypopnea index (AHI) of 10 or less during nocturnal PSG, and, in the
                  opinion of the investigator, nCPAP is effective therapy.

               -  Following demonstration of effectiveness, evidence of regular nCPAP usage must be
                  shown during a 2-week evaluation period (ie, nCPAP usage for at least 4
                  hours/night on at least 70% of the nights).

          6. The patient is in good health as determined by a medical and psychiatric history,
             physical examination, ECG, and serum chemistry and hematology.

          7. 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.

          8. The patient has a Clinical Global Impression of Severity of Illness (CGI-S) rating of
             4 or more.

          9. The patient has an ESS score of 10 or more.

         10. The patient does not have any medical or psychiatric disorders that could account for
             the excessive sleepiness.

         11. The patient is able to complete self rating scales and computer-based testing.

         12. The patient is willing and able to comply with study restrictions and to attend
             regularly scheduled clinic visits as specified in this protocol.

        Exclusion Criteria:

        Patients are excluded from participating in this study if 1 or more of the following
        criteria are met:

          1. has any clinically significant, uncontrolled medical or psychiatric conditions
             (treated or untreated)

          2. has a probable diagnosis of a current sleep disorder other than OSAHS

          3. consumes caffeine including coffee, tea and/or other caffeine containing beverages or
             food averaging more than 600 mg of caffeine per day

          4. 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

          5. 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)

          6. has a positive urine drug screen (UDS)

          7. has a clinically significant deviation from normal in the physical examination

          8. is a pregnant or lactating woman. (Any woman becoming pregnant during the study will
             be withdrawn from the study.)

          9. has used an investigational drug within 1 month before the initial screening visit

         10. has any disorder that may interfere with drug absorption, distribution, metabolism, or
             excretion (including gastrointestinal surgery)

         11. has a known clinically significant drug sensitivity to stimulants or modafinil