Clinical trial NCT00107848: PROVIGIL® (Modafinil) Treatment in Children and Adolescents With Excessive Sleepiness Associated With Narcolepsy or Obstructive Sleep Apnea/Hypopnea Syndrome
Official title: A 1 Year Open Label, Flexible Dosage Extension Study to Assess the Safety and Continued Effectiveness of PROVIGIL® (Modafinil) Treatment in Children and Adolescents With Excessive Sleepiness Associated With Narcolepsy or Obstructive Sleep Apnea/Hypopnea Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Narcolepsy
Sleep Apnea, Obstructive
Keywords: Pediatric Narcolepsy
Pediatric OSA
CPAP
Pediatric Narcolepsy or OSAHS
Lead sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
Sponsor class: INDUSTRY
First posted: 2005-04-11
Enrollment: 280
Sex: ALL
Minimum age (years): 6
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary objective of the study is to evaluate the safety and tolerability of treatment with PROVIGIL in children and adolescents with excessive sleepiness (ES) associated with narcolepsy or OSAHS (obstructive sleep apnea/hypopnea), when administered for up to 12 months. Safety and tolerability will be evaluated throughout the study by means of adverse event information, clinical laboratory test results, vital signs measurements, and body weight and height measurements; quarterly physical examination findings; and 12 lead electrocardiograph (ECG) evaluations at the end of the study. In addition, the cognitive and behavioral effects of PROVIGIL will be assessed quarterly as measured by the Child Behavior Checklist for Ages 6-18 (CBCL/6-18), a brief psychiatric interview, and the Kaufman Brief Intelligence Test (KBIT 2).

Detailed description: PROVIGIL is a registered trademark of Genelco, S.A., licensed to Cephalon, Inc.

Eligibility criteria: Inclusion Criteria:

* Appropriate written assent is obtained from the patient and written informed consent is obtained from the parent or legal guardian (defined by the IEC/IRB)
* A boy or girl aged 6 through 16 years (at the start of the previous double blind study), inclusive, who participated in study C1538/3027/NA/MN or C1538/3028/AP/MN
* Have a diagnosis (as established in the previous double blind study) of narcolepsy (or presumed narcolepsy) or OSAHS according to the criteria established by the International Classification of Sleep Disorders (ICSD) manual of the American Academy of Sleep Medicine (AASM)
* Continue to be in good health as determined by a medical and psychiatric history, ECGs, physical examination findings, serum chemistry, hematology, and urinalysis
* Have blood pressure values greater than those for the 5th percentile and less than the 95th percentile 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 who have a negative urine pregnancy test at the screening/baseline visit, must be using a medically acceptable method of birth control, and must agree to continued 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 contraceptives (oral, topical \[patch\], implanted, and injected) in conjunction with a barrier method; intrauterine device (IUD); or abstinence
* No positive urine drug screen (UDS) for any illicit drug or alcohol (ethanol) at baseline visit, unless a false positive is suspected, in which case the UDS will be repeated. If the patient has a positive drug screen for methylphenidate or amphetamine at screening, the patient must have a negative UDS after a washout period and prior to baseline.
* Have a parent or legal guardian who is willing to participate in the study
* Continue to meet inclusion criteria from the previous study, as appropriate

Exclusion Criteria:

* Have self induced sleep deprivation/poor sleep hygiene
* 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
* A clinically significant drug sensitivity to stimulants such as amphetamine, dextroamphetamine, methylphenidate, or pemoline; and modafinil or any of its components
* 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 ECG or physical examination findings, or clinical laboratory (ie, hematology, serum chemistry, urinalysis) test results at the screening/baseline visit
* Absolute neutrophil count (ANC) below the lower limit of normal at the baseline 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.)
* A seated pulse outside the range of 60 through 115 bpm after resting for 5 minutes
* A total daily intake of more than 500 mg of caffeine per day (eg, approximately ten 12 ounce caffeinated sodas, 5 cups of coffee or tea, or about 25 ounces of chocolate per day) within 1 week of the baseline visit
* Pregnant or lactating/nursing; any child who becomes pregnant during the study will be withdrawn.

Primary outcomes:
measure: The primary objective of the study is to evaluate the safety and tolerability of treatment with PROVIGIL in children and adolescents with excessive sleepiness (ES) associated with narcolepsy or OSAHS, when administered for up to 12 months.
Secondary outcomes:
measure: The secondary objective of the study is to evaluate long-term effectiveness by using: the Clinical Global Impression of Change (CGI C) ratings for severity of ES and the total score from the Pediatric Daytime Sleepiness Scale (PDSS)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Robert Doekel, Jr., M.D.
state: Alabama
city: Birmingham
country: United States
facility: Chris M. Makris, M.D.
state: Alabama
city: Phoenix
country: United States
facility: Barbara Harris, Ph.D.
state: Arizona
city: Tucson
country: United States
facility: Derek Loewy, Ph.D.
state: Arizona
city: Fort Smith
country: United States
facility: Joseph McCarty, M.D.
state: Arkansas
city: Little Rock
country: United States
facility: Samuel Boellner, M.D.
state: Arkansas
city: Huntington Beach
country: United States
facility: Julie Thompson-Dobkin, D.O.
state: California
city: Long Beach
country: United States
facility: Mark Buchfuhrer, M.D.
state: California
city: Los Angeles
country: United States
facility: Yury Furman, M.D.
state: California
city: Palm Springs
country: United States
facility: Stuart Menn, M.D.
state: California
city: Rolling Hills Estates
country: United States
facility: Lawrence Sher, M.D.
state: California
city: San Diego
country: United States
facility: Milton K. Erman, M.D.
state: California
city: Stanford
country: United States
facility: Jed Black, M.D.
state: California
city: Norwalk
country: United States
facility: Edward O'Malley
state: Connecticut
city: Gainesville
country: United States
facility: Elias H. Sarkis
state: Florida
city: Miami
country: United States
facility: Americo Padilla, M.D.
state: Florida
city: Naples
country: United States
facility: Martin A. Cohn, M.D.
state: Florida
city: Atlanta
country: United States
facility: D. Alan Lankford, Ph.D.
state: Georgia
city: Atlanta
country: United States
facility: Gary Montgomery, M.D.
state: Georgia
city: Atlanta
country: United States
facility: Jerry Silverboard, M.D.
state: Georgia
city: Macon
country: United States
facility: Charles Wells, Jr., M.D.
state: Georgia
city: Savannah
country: United States
facility: Joel Greenberg
state: Georgia
city: Stockbridge
country: United States
facility: Robert M. Cohen
state: Georgia
city: Chicago
country: United States
facility: Stephen H. Sheldon, D.O., FAAP
state: Illinois
city: Chicago
country: United States
facility: Michael Kohrman, M.D.
state: Illinois
city: Danville
country: United States
facility: James Cook, M.D.
state: Indiana
city: Topeka
country: United States
facility: William Leeds, D.O.
state: Kansas
city: Louisville
country: United States
facility: Karen Waters, M.D.
state: Kentucky
city: Shreveport
country: United States
facility: Margaret Ann Springer, M.D.
state: Louisiana
city: Chevy Chase
country: United States
facility: Helene A. Emsellem, M.D.
state: Maryland
city: Frederick
country: United States
facility: Marc Raphaelson
state: Maryland
city: Flint
country: United States
facility: George Zureikat, M.D.
state: Michigan
city: Hattiesburg
country: United States
facility: John Harsh, Ph.D., DABSM
state: Mississippi
city: Reno
country: United States
facility: William Torch, M.D., MS
state: Nevada
city: Mount Laurel
country: United States
facility: Kathleen Ryan, M.D.
state: New Jersey
city: Newark
country: United States
facility: Monroe Karetzky, M.D.
state: New Jersey
city: Princeton
country: United States
facility: Lee Brooks, M.D.
state: New Jersey
city: Trenton
country: United States
facility: Marc Seelagy, M.D.
state: New Jersey
city: New York
country: United States
facility: Gary Zammit, M.D.
state: New York
city: Cleveland
country: United States
facility: Carol Rosen
state: Ohio
city: Toledo
country: United States
facility: Michael Neeb, Ph.D.
state: Ohio
city: Toledo
country: United States
facility: Ramalinga Reddy
state: Ohio
city: Oklahoma City
country: United States
facility: William C. Orr, Ph.D.
state: Oklahoma
city: Oklahoma City
country: United States
facility: Jorg Pahl, M.D.
state: Oklahoma
city: Providence
country: United States
facility: Judith Owens, M.D., MPH
state: Rhode Island
city: Columbia
country: United States
facility: Richard Bogan, M.D., FCCP
state: South Carolina
city: Morristown
country: United States
facility: Julie Jacques, D.O.
state: Tennessee
city: Austin
country: United States
facility: John Hudson, M.D.
state: Texas
city: Dallas
country: United States
facility: David Sperry, M.D.
state: Texas
city: Houston
country: United States
facility: Todd J. Swick, M.D.
state: Texas
city: San Antonio
country: United States
facility: Jerry J. Tomasovic, M.D.
state: Texas
city: Salt Lake City
country: United States
facility: Radiant Research, Salt Lake City
state: Utah
city: Salt Lake City
country: United States
facility: James M. Ferguson, M.D.
state: Utah
city: Fairfax
country: United States
facility: James Perlstrom
state: Virginia
city: Seattle
country: United States
facility: Robert J. Reichler
state: Washington
city: Calgary
country: Canada
facility: Adam Moscovitch, M.D.
state: Alberta
city: Edmonton
country: Canada
facility: Manisha Witmans
state: Alberta
city: Parry Sound
country: Canada
facility: Lawrence Reinish
state: Ontario
city: Scarborough
country: Canada
facility: Leonid Kayumov, M.D.
state: Ontario
city: Toronto
country: Canada
facility: Mortimer Mamelak, M.D.
state: Ontario
city: Toronto
country: Canada
facility: Colin Shapiro, Ph.D.
state: Ontario
Study officials:
References: