MedPath

Study of PROVIGIL ® (Modafinil) Treatment in Children and Adolescents With Excessive Sleepiness Associated With Narcolepsy

Phase 3
Completed
Conditions
Narcolepsy
Registration Number
NCT00107796
Lead Sponsor
Cephalon
Brief Summary

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 post-baseline observation (week 6 or early termination).

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
140
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Primary Outcome Measures
NameTimeMethod
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 Outcome Measures
NameTimeMethod
Clinical Global Impression of Change (CGI-C) ratings for ES at weeks 3 and 6
Total score from the Pediatric Daytime Sleepiness Scale (PDSS) at weeks 3 and 6, and last postbaseline observation
Mean sleep latency from the MSLT (average of 4 naps performed at 0900, 1100, 1300, and 1500) at week 6

Trial Locations

Locations (72)

Joseph McCarty, M.D.

🇺🇸

Fort Smith, Arkansas, United States

Anna Ivanenko, M.D., Ph.D.

🇺🇸

Maywood, Illinois, United States

Carol Rosen, M.D.

🇺🇸

Cleveland, Ohio, United States

Stephen H. Sheldon, D.O., FAAP

🇺🇸

Chicago, Illinois, United States

Gary Montgomery, M.D.

🇺🇸

Atlanta, Georgia, United States

Michael Kohrman, M.D.

🇺🇸

Chicago, Illinois, United States

Martin Scharf, Ph.D.

🇺🇸

Cincinnati, Ohio, United States

Stephen Brooks, M.D.

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San Francisco, California, United States

Amerigo Padilla, M.D.

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Miami, Florida, United States

Todd J. Swick, M.D.

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Houston, Texas, United States

James M. Ferguson, M.D.

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Salt Lake City, Utah, United States

Julie Thompson-Dobkin, D.O.

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Huntington Beach, California, United States

Mark Buchfuhrer, M.D.

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Long Beach, California, United States

Yury Furman, M.D.

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Los Angeles, California, United States

John L. Carroll, M.D.

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Little Rock, Arkansas, United States

Richard Shubin, M.D.

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Pasadena, California, United States

Stuart Quan, M.D.

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Tucson, Arizona, United States

Lawrence Sher, M.D.

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Rolling Hills Estates, California, United States

Markus H. Schmidt, M.D., Ph.D.

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Dublin, Ohio, United States

Milton K. Erman, M.D.

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San Diego, California, United States

Bruce Corser, M.D.

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Cincinnati, Ohio, United States

James Lee, M.D.

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Charlotte, North Carolina, United States

Michael Neeb, Ph.D.

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Toledo, Ohio, United States

Monroe Karetzky, M.D.

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Newark, New Jersey, United States

Jeffery Gould, M.D.

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Bethlehem, Pennsylvania, United States

Judith Owens, M.D., MPH

🇺🇸

Providence, Rhode Island, United States

Allen Denys, M.D.

🇨🇦

Windsor, Ontario, Canada

John Hudson, M.D.

🇺🇸

Austin, Texas, United States

Marc Seelagy, M.D.

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Trenton, New Jersey, United States

Richard Bogan, M.D., FCCP

🇺🇸

Columbia, South Carolina, United States

David Sperry, M.D.

🇺🇸

Dallas, Texas, United States

Raouf Amin, MD

🇺🇸

Cincinnati, Ohio, United States

Gary Zammit, M.D.

🇺🇸

New York, New York, United States

Julie Jacques, D.O.

🇺🇸

Morristown, Tennessee, United States

Dainis Irbe, M.D.

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Eugene, Oregon, United States

Lee Brooks, M.D.

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Philadelphia, Pennsylvania, United States

William Pistone, M.D.

🇺🇸

Allentown, Pennsylvania, United States

Mortimer Mamelak, M.D.

🇨🇦

Toronto, Ontario, Canada

Adam Moscovitch, M.D.

🇨🇦

Calgary, Alberta, Canada

Jerry J. Tomasovic, M.D.

🇺🇸

San Antonio, Texas, United States

Robert Doekel, Jr., M.D.

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Birmingham, Alabama, United States

Chris M. Makris, M.D.

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Birmingham, Alabama, United States

Barbara Harris, Ph.D.

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Phoenix, Arizona, United States

William C. Orr, Ph.D.

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Oklahoma City, Oklahoma, United States

Jorg Pahl, M.D.

🇺🇸

Oklahoma City, Oklahoma, United States

Derek Loewy, Ph.D.

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Tucson, Arizona, United States

Stuart Menn, M.D.

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Palm Springs, California, United States

Jed Black, M.D.

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Stanford, California, United States

Paul Haberman, M.D.

🇺🇸

Santa Monica, California, United States

Martin A. Cohn, M.D.

🇺🇸

Naples, Florida, United States

D. Alan Lankford, Ph.D.

🇺🇸

Atlanta, Georgia, United States

Charles Wells, Jr., M.D.

🇺🇸

Macon, Georgia, United States

James Cook, M.D.

🇺🇸

Danville, Indiana, United States

Jerry Silverboard, M.D.

🇺🇸

Atlanta, Georgia, United States

Henry Lahmeyer, M.D.

🇺🇸

Northfield, Illinois, United States

Helene A. Emsellem, M.D.

🇺🇸

Chevy Chase, Maryland, United States

John Harsh, Ph.D., DABSM

🇺🇸

Hattiesburg, Mississippi, United States

Margaret Ann Springer, M.D.

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Shreveport, Louisiana, United States

Marc Raphaelson, M.D.

🇺🇸

Frederick, Maryland, United States

William Torch, M.D., MS

🇺🇸

Reno, Nevada, United States

Sushmita Mikkilineni, M.D.

🇺🇸

New Brunswick, New Jersey, United States

Kathleen Ryan, M.D.

🇺🇸

Mount Laurel, New Jersey, United States

Ralph A. Pascualy, M.D.

🇺🇸

Seattle, Washington, United States

Guillermo Borrero, M.D.

🇺🇸

Clairton, Pennsylvania, United States

Leonid Kayumov, M.D.

🇨🇦

Scarborough, Ontario, Canada

Colin Shapiro, Ph.D.

🇨🇦

Toronto, Ontario, Canada

William Leeds, D.O.

🇺🇸

Topeka, Kansas, United States

George Zureikat, M.D.

🇺🇸

Flint, Michigan, United States

Pradeep Sahota, M.D.

🇺🇸

Columbia, Missouri, United States

Karen Waters, M.D.

🇺🇸

Louisville, Kentucky, United States

Daniela Minecan, M.D.

🇺🇸

Ann Arbor, Michigan, United States

Samuel Boellner, M.D.

🇺🇸

Little Rock, Arkansas, United States

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