Primary Objectives: 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 narcolepsy, 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
Inclusion Criteria:
Diagnosis and Main Criteria for Inclusion (Patients are included in the study if all of the
following criteria are met):
- 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
narcolepsy (or presumed narcolepsy) as assessed by all of the following: *clinical
history;
- NPSG (nocturnal polysomnogram) (as evaluated by the investigator) to rule out
other sleep disorders (ie, obstructive sleep apnea/hypopnea syndrome [OSAHS] or
periodic limb movement with sleep [PLMs]);
- narcolepsy (or presumed narcolepsy) as identified by at least 1 of the following:
MSLT (as evaluated by the investigator) (mean sleep latency [from 4 naps] <10
minutes); 2 sleep onset REM periods (SOREMP); cataplexy; sleep paralysis;
hypnogogic hallucinations - OR- *have a previous diagnosis of narcolepsy on the
basis of NPSG and/or MSLT at any time before the screening visit
- Have ES (MSLT <10 minutes and/or CGI S ≥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
- 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 a washout period and before the
baseline visit
- Have a parent or legal guardian who is willing to participate in the study
Exclusion Criteria:
Main Criteria for Exclusion (Patients are excluded from participating in this study if 1 or
more of the following criteria are met):
- 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 a history of suicide attempt, or are at suicidal risk
- Have an average of 5 or more apneic/hypopneic episodes per hour of nocturnal sleep as
assessed by NPSG at the baseline visit
- 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 (Note:
Medications for the treatment of cataplexy will be permitted if the patient has been
on a stable dose for at least 1 month.)
- Use of any MAO (monoamine oxidase) inhibitors or SSRIs (Selective Serotonin Reuptake
Inhibitors) within 2 weeks of the baseline visit (unless used for cataplexy)
- 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
Robert Doekel, Jr., M.D., Birmingham, Alabama 35213, United States
Chris M. Makris, M.D., Birmingham, Alabama 35233, United States
Adam Moscovitch, M.D., Calgary, Alberta T2X2A8, Canada
Barbara Harris, Ph.D., Phoenix, Arizona 85050, United States
Derek Loewy, Ph.D., Tucson, Arizona 85712, United States
Stuart Quan, M.D., Tucson, Arizona 85724, United States
Samuel Boellner, M.D., Little Rock, Arkansas 72205, United States
John L. Carroll, M.D., Little Rock, Arkansas 72202, United States
Joseph McCarty, M.D., Fort Smith, Arkansas 72913, United States
Jed Black, M.D., Stanford, California 94305, United States
Stephen Brooks, M.D., San Francisco, California 94109, United States
Mark Buchfuhrer, M.D., Long Beach, California 90806, United States
Milton K. Erman, M.D., San Diego, California 92121, United States
Yury Furman, M.D., Los Angeles, California 90048, United States
Paul Haberman, M.D., Santa Monica, California 90404, United States
Lawrence Sher, M.D., Rolling Hills Estates, California 90274, United States
Richard Shubin, M.D., Pasadena, California 91105, United States
Stuart Menn, M.D., Palm Springs, California 92262, United States
Julie Thompson-Dobkin, D.O., Huntington Beach, California 92648, United States
Martin A. Cohn, M.D., Naples, Florida 34110, United States
Amerigo Padilla, M.D., Miami, Florida 33173, United States
D. Alan Lankford, Ph.D., Atlanta, Georgia 30342, United States
Gary Montgomery, M.D., Atlanta, Georgia 30342, United States
Jerry Silverboard, M.D., Atlanta, Georgia 30342, United States
Charles Wells, Jr., M.D., Macon, Georgia 31208, United States
Anna Ivanenko, M.D., Ph.D., Maywood, Illinois 60153, United States
Michael Kohrman, M.D., Chicago, Illinois 60637, United States
Henry Lahmeyer, M.D., Northfield, Illinois 60093, United States
Stephen H. Sheldon, D.O., FAAP, Chicago, Illinois 60614, United States
James Cook, M.D., Danville, Indiana 46122, United States
William Leeds, D.O., Topeka, Kansas 66606, United States
Karen Waters, M.D., Louisville, Kentucky 40202, United States
Margaret Ann Springer, M.D., Shreveport, Louisiana 71103, United States
Helene A. Emsellem, M.D., Chevy Chase, Maryland 20815, United States
Marc Raphaelson, M.D., Frederick, Maryland 21702, United States
Daniela Minecan, M.D., Ann Arbor, Michigan 48109, United States
George Zureikat, M.D., Flint, Michigan 48503, United States
John Harsh, Ph.D., DABSM, Hattiesburg, Mississippi 39401, United States
Pradeep Sahota, M.D., Columbia, Missouri 65212, United States
William Torch, M.D., MS, Reno, Nevada 89502, United States
Lee Brooks, M.D., Princeton, New Jersey 08540, United States
Monroe Karetzky, M.D., Newark, New Jersey 07112, United States
Sushmita Mikkilineni, M.D., New Brunswick, New Jersey 08903, United States
Kathleen Ryan, M.D., Mount Laurel, New Jersey 08054, United States
Marc Seelagy, M.D., Trenton, New Jersey 08629, United States
Gary Zammit, M.D., New York, New York 10025, United States
James Lee, M.D., Charlotte, North Carolina 28226, United States
Raouf Amin, MD, Cincinnati, Ohio 45229, United States
Michael Neeb, Ph.D., Toledo, Ohio 43608, United States
Martin Scharf, Ph.D., Cincinnati, Ohio 45246, United States
Markus H. Schmidt, M.D., Ph.D., Dublin, Ohio 43017, United States
Carol Rosen, M.D., Cleveland, Ohio 44106, United States
Bruce Corser, M.D., Cincinnati, Ohio 45219, United States
William C. Orr, Ph.D., Oklahoma City, Oklahoma 73112, United States
Jorg Pahl, M.D., Oklahoma City, Oklahoma 73118, United States
Allen Denys, M.D., Windsor, Ontario N9A1C9, Canada
Leonid Kayumov, M.D., Scarborough, Ontario M1S1T7, Canada
Mortimer Mamelak, M.D., Toronto, Ontario M2J2K9, Canada
Colin Shapiro, Ph.D., Toronto, Ontario M5T2S8, Canada
Dainis Irbe, M.D., Eugene, Oregon 97401, United States
Guillermo Borrero, M.D., Clairton, Pennsylvania 15025, United States
Lee Brooks, M.D., Philadelphia, Pennsylvania 19104, United States
Jeffery Gould, M.D., Bethlehem, Pennsylvania 18015, United States
William Pistone, M.D., Allentown, Pennsylvania 18104, United States
Judith Owens, M.D., MPH, Providence, Rhode Island 02903, United States
Richard Bogan, M.D., FCCP, Columbia, South Carolina 29201, United States
Julie Jacques, D.O., Morristown, Tennessee 37814, United States
John Hudson, M.D., Austin, Texas 78756, United States
David Sperry, M.D., Dallas, Texas 75230, United States
Todd J. Swick, M.D., Houston, Texas 77024, United States
Jerry J. Tomasovic, M.D., San Antonio, Texas 78258, United States
James M. Ferguson, M.D., Salt Lake City, Utah 84107, United States
Ralph A. Pascualy, M.D., Seattle, Washington 98122, United States
