The primary objectives of the study are to determine the effectiveness of PROVIGIL treatment, compared to placebo treatment, in children and adolescents with excessive sleepiness (ES) associated with obstructive sleep apnea/hypopnea syndrome (OSAHS), as assessed by:

• mean sleep latency from the Multiple Sleep Latency Test (MSLT) (average of 4 naps performed at 0900, 1100, 1300, and 1500) at the last post baseline observation (week 6 or early termination)
• the Clinical Global Impression of Change (CGI–C) ratings for ES, at the last post baseline observation (week 6 or early termination).

Condition	Treatment or Intervention	Phase
Sleep Apnea, Obstructive	Drug: Modafinil	Phase III

Further Study Details: 

Primary Outcomes: Mean sleep latency from the Multiple Sleep Latency Test (MSLT) (average of 4 naps performed at 0900, 1100, 1300, and 1500) at the last post baseline observation (week 6 or early termination); The Clinical Global Impression of Change (CGI–C) ratings for ES, at the last post baseline observation (week 6 or early termination)
Secondary Outcomes: The Clinical Global Impression of Change (CGI-C) ratings for severity of ES; The total score from the Pediatric Daytime Sleepiness Scale (PDSS)
Expected Total Enrollment:  140

PROVIGIL is a trademark of Genelco, SA, licensed to Cephalon, Inc.

Ages Eligible for Study:  6 Years   -   16 Years,  Genders Eligible for Study:  Both

Accepts Healthy Volunteers

Criteria

Inclusion Criteria:

• Written informed consent/assent is obtained
• A boy or girl aged 6 through 16 years, inclusive
• Meet the minimal criteria established by the International Classification of Sleep Disorders (ICSD) manual of the American Academy of Sleep Medicine (AASM) for OSAHS as assessed by all of the following: *clinical history; *have a previous diagnosis of OSAHS on the basis of NPSG (nocturnal polysomnogram) and/or MSLT at any time before the screening visit. If the patient is a current user of CPAP (continuous positive airway pressure) therapy and is appropriately titrated on CPAP, the AHI ≥5 inclusion criterion is not applicable; *NPSG (nocturnal polysomnogram) (as evaluated by the investigator) to rule out other sleep disorders (ie, narcolepsy and periodic limb movement with sleep [PLMs]).
• Have ES (CGI-S [Clinical Global Impression of Severity] ≥4) that is not a direct result of inadequate sleep hygiene or other medical disorder
• Are in good health as determined by a medical and psychiatric history, physical examination, ECG, and clinical laboratory tests
• For patients who are not current users of CPAP therapy or who are not appropriately titrated on CPAP: have an average of 5 or more apneic/hypopneic episodes per hour of nocturnal sleep, as assessed by the NPSG at the baseline visit (AHI [apnea/hypopnea index] ≥5)
• Are currently users of CPAP therapy or have tried and not tolerated the current standards of care for OSAHS and continue to have residual sleepiness (ie, patients who comply with CPAP use, patients who are unable to tolerate or comply with CPAP therapy, patients who have had surgical removal of tonsils and adenoids or for whom this surgery is not warranted, and patients who have attempted or are on an ongoing weight loss program)
• Have an O2 saturation of at least 85%, based on the investigator’s assessment of the patient’s health
• Have blood pressure values greater than those for the 5th percentile and less than the 95th percentile for age on the National High Blood Pressure Education Program guidelines for blood pressure levels for boys and girls ages 6 through 16 years
• Girls who are post menarche or sexually active must have a negative urine pregnancy test prior to the baseline visit, must be using a medically acceptable method of birth control, 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 birth control include: barrier method with spermicide; steroidal contraceptive (eg, oral, transdermal, implanted, or injected) in conjunction with a barrier method; intrauterine device (IUD); or abstinence.
• Be able to swallow a placebo tablet the same size and shape as the study drug tablet
• Negative UDS (urine drug screen) for any illicit drug, alcohol (ethanol), stimulants, or modafinil at screening; if positive for stimulants or modafinil (prescribed for ES) at the screening visit, UDS to be repeated after washout period and before the baseline visit
• Have a parent or legal guardian who is willing to participate in the study

Exclusion Criteria:

• Have any other disorder(s) that could be considered the primary cause of ES (eg, self induced sleep deprivation)
• Have a past or present seizure disorder (except history of a single febrile seizure), a history of psychosis, or of clinically significant head trauma (eg, brain damage) or past neurosurgery
• Have periodic limb movement (PLM) arousal index greater than 5 (ie, >5 PLMs with arousals per hour of sleep)
• Have a history of suicide attempt, or are at suicidal risk
• A clinically significant drug sensitivity to stimulants such as amphetamine, dextroamphetamine, methylphenidate, or pemoline; and/or modafinil or any of its components
• Use of any prescription (eg, clonidine, guanfacine) or nonprescription (over the counter [OTC]) medications, including dietary supplements with psychoactive properties (eg, any OTC medications or supplements containing ephedrine [ie, ma huang or ephedra], pseudoephedrine, caffeine, or phenylpropanolamine) or sedating properties (ie, antihistamines or sedative hypnotics) within 1 week of the baseline visit
• Use of any MAO (monoamine oxidase) inhibitors or SSRIs (selective serotonin reuptake inhibitors) within 2 weeks of the baseline visit
• Received any investigational drug (except modafinil) within 4 weeks of the baseline visit
• Any disorder that could interfere with drug absorption, distribution, metabolism, or excretion (including previous gastrointestinal surgery)
• Active, clinically significant gastrointestinal, cardiovascular, hepatic, renal, hematologic, neoplastic, endocrine, neurologic, immunodeficiency, pulmonary, or other major clinically significant disorder/disease
• Any clinically significant deviation from the normal range(s) in the physical examination or ECG findings, or clinical laboratory test results (ie, serum chemistry, hematology, and urinalysis) at the screening or baseline visit
• ANC (absolute neutrophil count) below the lower limit of normal at the screening visit (NOTE: If the ANC is below the lower limit of normal at the baseline visit, the medical monitor will be consulted for continued eligibility in the study.)
• Seated pulse outside the range of 60 through 115 bpm after resting for 5 minutes
• A history of alcohol, narcotic, or any other substance abuse or dependence as defined by the Diagnostic and Statistical Manual of the American Psychiatric Association, 4th Edition (DSM IV) criteria
• A total daily intake of more than 250 mg of caffeine per day (eg, approximately five 12 ounce caffeinated sodas, 2.5 cups of coffee or tea, or about 12.5 ounces of chocolate per day) within 1 week of the baseline visit
• Pregnant or lactating/nursing girl; any girl who becomes pregnant during the study will be withdrawn
• A clinically significant illness within 4 weeks of the baseline visit; or is symptomatic for any clinically significant illness at the screening or baseline visit.

Patrick Young      610-738-6587    pjyoung@cephalon.com
Nancy Harvey      610-738-6615    nharvey@cephalon.com

Alabama
      Robert Doekel, Jr., M.D., Birmingham,  Alabama,  35213,  United States; Recruiting
Arizona
      Derek Loewy, Ph.D., Tucson,  Arizona,  85712,  United States; Not yet recruiting
      Stuart Quan, M.D., Tucson,  Arizona,  85724,  United States; Not yet recruiting
Arkansas
      John L. Carroll, M.D., Little Rock,  Arkansas,  72202,  United States; Not yet recruiting
      Joseph McCarty, M.D., Fort Smith,  Arkansas,  72913,  United States; Recruiting
California
      Jed Black, M.D., Stanford,  California,  94305,  United States; Not yet recruiting
      Julie Thompson-Dobkin, D.O., Huntington Beach,  California,  92648,  United States; Not yet recruiting
      Lawrence Sher, M.D., Rolling Hills Estates,  California,  90274,  United States; Not yet recruiting
      Mark Buchfuhrer, M.D., Long Beach,  California,  90806,  United States; Not yet recruiting
      Milton K. Erman, M.D., San Diego,  California,  92121,  United States; Not yet recruiting
      Paul Haberman, M.D., Santa Monica,  California,  90404,  United States; Not yet recruiting
      Richard Shubin, M.D., Pasadena,  California,  91105,  United States; Not yet recruiting
      Stephen Brooks, M.D., San Francisco,  California,  94109,  United States; Not yet recruiting
      Stuart Menn, M.D., Palm Springs,  California,  92262,  United States; Not yet recruiting
      Yury Furman, M.D., Los Angeles,  California,  90048,  United States; Not yet recruiting
Florida
      Amerigo Padilla, M.D., Miami,  Florida,  33173,  United States; Not yet recruiting
      Martin A. Cohn, M.D., Naples,  Florida,  34110,  United States; Not yet recruiting
Georgia
      D. Alan Lankford, Ph.D., Atlanta,  Georgia,  30342,  United States; Recruiting
      Gary Montgomery, M.D., Atlanta,  Georgia,  30342,  United States; Recruiting
      Jerry Silverboard, M.D., Atlanta,  Georgia,  30342,  United States; Not yet recruiting
Illinois
      Anna Ivanenko, M.D., Ph.D., Maywood,  Illinois,  60153,  United States; Not yet recruiting
      Henry Lahmeyer, M.D., Northfield,  Illinois,  60093,  United States; Not yet recruiting
      Michael Kohrman, M.D., Chicago,  Illinois,  60637,  United States; Not yet recruiting
      Stephen H. Sheldon, D.O., FAAP, Chicago,  Illinois,  60614,  United States; Not yet recruiting
Indiana
      James Cook, M.D., Danville,  Indiana,  46122,  United States; Not yet recruiting
Kansas
      William Leeds, D.O., Topeka,  Kansas,  66606,  United States; Not yet recruiting
Kentucky
      Karen Waters, M.D., Louisville,  Kentucky,  40202,  United States; Not yet recruiting
Louisiana
      Margaret Ann Springer, M.D., Shreveport,  Louisiana,  71103,  United States; Not yet recruiting
Maryland
      Helene A. Emsellem, M.D., Chevy Chase,  Maryland,  20815,  United States; Not yet recruiting
      Marc Raphaelson, M.D., Frederick,  Maryland,  21702,  United States; Not yet recruiting
Michigan
      Daniela Minecan, M.D., Ann Arbor,  Michigan,  48109,  United States; Not yet recruiting
      George Zureikat, M.D., Flint,  Michigan,  48503,  United States; Not yet recruiting
Missouri
      Pradeep Sahota, M.D., Columbia,  Missouri,  65212,  United States; Not yet recruiting
Nevada
      William Torch, M.D., MS, Reno,  Nevada,  89502,  United States; Not yet recruiting
New Jersey
      Kathleen Ryan, M.D., Mount Laurel,  New Jersey,  08054,  United States; Not yet recruiting
      Lee Brooks, M.D., Princeton,  New Jersey,  08540,  United States; Not yet recruiting
      Marc Seelagy, M.D., Trenton,  New Jersey,  08629,  United States; Not yet recruiting
      Monroe Karetzky, M.D., Newark,  New Jersey,  07112,  United States; Recruiting
      Sushmita Mikkilineni, M.D., New Brunswick,  New Jersey,  08903,  United States; Not yet recruiting
New York
      Gary Zammit, M.D., New York,  New York,  10025,  United States; Not yet recruiting
North Carolina
      James Lee, M.D., Charlotte,  North Carolina,  28226,  United States; Not yet recruiting
Ohio
      Markus H. Schmidt, M.D., Ph.D., Dublin,  Ohio,  43017,  United States; Not yet recruiting
      Martin Scharf, Ph.D., Cincinnati,  Ohio,  45246,  United States; Not yet recruiting
      Michael Neeb, Ph.D., Toledo,  Ohio,  43608,  United States; Not yet recruiting
      Raouf Amin, MD, Cincinnati,  Ohio,  45229,  United States; Not yet recruiting
Oklahoma
      Jorg Pahl, M.D., Oklahoma City,  Oklahoma,  73118,  United States; Recruiting
      William C. Orr, Ph.D., Oklahoma City,  Oklahoma,  73112,  United States; Not yet recruiting
Oregon
      Dainis Irbe, M.D., Eugene,  Oregon,  97401,  United States; Not yet recruiting
Pennsylvania
      Guillermo Borrero, M.D., Clairton,  Pennsylvania,  15025,  United States; Not yet recruiting
      Jeffery Gould, M.D., Bethlehem,  Pennsylvania,  18015,  United States; Not yet recruiting
      William Pistone, M.D., Allentown,  Pennsylvania,  18104,  United States; Not yet recruiting
Rhode Island
      Judith Owens, M.D., MPH, Providence,  Rhode Island,  02903,  United States; Recruiting
South Carolina
      Richard Bogan, M.D., FCCP, Columbia,  South Carolina,  29201,  United States; Recruiting
Tennessee
      Julie Jacques, D.O., Morristown,  Tennessee,  37814,  United States; Not yet recruiting
Texas
      David Sperry, M.D., Dallas,  Texas,  75230,  United States; Not yet recruiting
      Jerry J. Tomasovic, M.D., San Antonio,  Texas,  78258,  United States; Recruiting
      John Hudson, M.D., Austin,  Texas,  78756,  United States; Not yet recruiting
      Todd J. Swick, M.D., Houston,  Texas,  77024,  United States; Recruiting
Utah
      James M. Ferguson, M.D., Salt Lake City,  Utah,  84107,  United States; Recruiting
Washington
      Ralph A. Pascualy, M.D., Seattle,  Washington,  98122,  United States; Not yet recruiting
Canada, Alberta
      Adam Moscovitch, M.D., Calgary,  Alberta,  T2X2A8,  Canada; Not yet recruiting
Canada, Ontario
      Allen Denys, M.D., Windsor,  Ontario,  N9A1C9,  Canada; Not yet recruiting
      Leonid Kayumov, M.D., Scarborough,  Ontario,  M1S1T7,  Canada; Not yet recruiting
      Mortimer Mamelak, M.D., Toronto,  Ontario,  M2J2K9,  Canada; Recruiting

Study ID Numbers:  C1538/3028/AP/MN-OSAHS
Record last reviewed:  March 2005
Last Updated:  April 11, 2005
Record first received:  April 8, 2005
ClinicalTrials.gov Identifier:  NCT00107809
Health Authority: United States: Food and Drug Administration; Health Canada (Awaiting confirmation)
ClinicalTrials.gov processed this record on 2005-04-14