Study to Evaluate Armodafinil Treatment in Improving Prefrontal Cortical Activation and Working Memory Performance
Condition: Excessive Sleepiness
MeSH terms: Disorders of Excessive Somnolence; Sleepiness
Intervention: Armodafinil; Placebo
Intervention description: Armodafinil once-daily (50 mg/day (1 tablet) on Day 1; increased to 100 mg/day (2 tablets) starting on Day 2; increased to 150 mg/day (3 tablets) starting on Day 5; increased to 200 mg/day (4 tablets) starting on Day 8). Then continue 200 mg/day dosage through Day 14.; Matching Placebo dosed once-daily (50 mg/day (1 tablet) on Day 1; increased to 100 mg/day (2 tablets) starting on Day 2; increased to 150 mg/day (3 tablets) starting on Day 5; increased to 200 mg/day (4 tablets) starting on Day 8). Then continue 200 mg/day dosage through Day 14.
Intervention MeSH terms: Modafinil
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 40.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: No

Summary:

      The primary objective of this study is to determine whether treatment with armodafinil will
      provide improvements in prefrontal cortical activation in patients with OSAHS (Obstructive
      Sleep Apnea/Hypopnea Syndrome) who have residual sleepiness despite receiving nCPAP therapy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patient has a current diagnosis of OSAHS and has a complaint of excessive sleepiness
             despite effective nCPAP therapy.

          -  Patient has excessive sleepiness as evidenced by a mean sleep latency of less than 8
             minutes, as determined by the MSLT.

          -  Patient has an ESS score of 10 or more at the initial screening visit.

          -  Patient has a habitual sleep time beginning no earlier than 2100 and ending no later
             than 0700.

          -  Patient is right-handed. Patients who are ambidextrous may be eligible following
             consultation with the medical monitor.

          -  Women of childbearing potential 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.

          -  Patient exhibits reasonable accuracy (≥80%) on the 2-back working memory task during
             the training session at the second screening visit.

        Exclusion Criteria:

        The Patient:

          -  The patient is a current smoker or has a prior history of smoking (defined as ≥1
             pack-year) within 2 years prior to the screening visit.

          -  consumes caffeine including coffee, tea and/or other caffeine-containing beverages or
             food averaging more than 400 mg of caffeine per day (approximately equivalent to 4 or
             more cups of coffee).

          -  has NART-predicted verbal IQ and QIDS-SR16 scores within protocol-specific
             exclusionary ranges.

          -  has a clinically significant, uncontrolled medical or psychiatric conditions (treated
             or untreated).

          -  has a confirmed or probable diagnosis of a current sleep disorder other than OSAHS.

          -  has used any excluded prescription drugs or procedures for prohibited and allowed
             drugs within the excluded timeframe.

          -  has a history of alcohol, narcotic, or any other drug abuse.

          -  has a positive UDS, without medical explanation, at the screening visit.

          -  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 a past or present seizure disorder, head trauma that is clinically significant, or
             past neurosurgery.

          -  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 hypersensitivity to armodafinil or modafinil, or any other component of
             the study drug tablets.

          -  has a history of any clinically significant cutaneous drug reaction, or a history of
             clinically significant hypersensitivity reaction, including multiple allergies or drug
             reactions.

          -  has known human immunodeficiency virus (HIV).

          -  has clinical laboratory test value(s) outside the range(s) specified in the Protocol,
             or presents a clinically significant laboratory abnormality without prior written
             approval by the medical monitor.

          -  has worked the night shift within 28 days of the baseline visit, or will work the
             night shift during the double-blind segment of the study.

          -  anticipates any travel across more than 3 time zones at any time during the study.

          -  needs to use any of the excluded medications identified in this protocol.

          -  is unable to complete neuroimaging studies, performance tasks, self-rating scales, and
             all other study assessments.

          -  has a contraindication to fMRI scanning, (such as an implanted
             pacemaker/defibrillator, aneurysm clips, drug infusion device or metallic foreign
             body).

          -  is suspected to be unable to tolerate fMRI scanning (eg, claustrophobic) and/or the
             testing paradigm.

          -  has physical or other characteristics that suggest imaging data will be unobtainable
             or degraded.