Clinical trial NCT00107809: Study of PROVIGIL ® (Modafinil) Treatment in Children and Adolescents With Excessive Sleepiness Associated With Obstructive Sleep Apnea/Hypopnea Syndrome
Official title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Assess the Efficacy and Safety of PROVIGIL ® (Modafinil) Treatment (100, 200, and 400 mg/Day) in Children and Adolescents With Excessive Sleepiness Associated With Obstructive Sleep Apnea/Hypopnea Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Sleep Apnea, Obstructive
Keywords: Pediatric Obstructive sleep Apnea
Excessive sleepiness
CPAP
Pediatric OSAHS
Lead sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
Sponsor class: INDUSTRY
First posted: 2005-04-11
Enrollment: 140
Sex: ALL
Minimum age (years): 6
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).

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

Eligibility criteria: Inclusion Criteria:

* 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.

Primary outcomes:
measure: 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)
measure: The Clinical Global Impression of Change (CGI-C) ratings for ES, at the last post baseline observation (week 6 or early termination)
Secondary outcomes:
measure: The Clinical Global Impression of Change (CGI-C) ratings for severity of ES
measure: 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: Tucson
country: United States
facility: Derek Loewy, Ph.D.
state: Arizona
city: Tucson
country: United States
facility: Stuart Quan, M.D.
state: Arizona
city: Fort Smith
country: United States
facility: Joseph McCarty, M.D.
state: Arkansas
city: Little Rock
country: United States
facility: John L. Carroll, 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: Pasadena
country: United States
facility: Richard Shubin, 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: San Francisco
country: United States
facility: Stephen Brooks, M.D.
state: California
city: Santa Monica
country: United States
facility: Paul Haberman, M.D.
state: California
city: Stanford
country: United States
facility: Jed Black, M.D.
state: California
city: Miami
country: United States
facility: Amerigo 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: 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: Maywood
country: United States
facility: Anna Ivanenko, M.D., Ph.D.
state: Illinois
city: Northfield
country: United States
facility: Henry Lahmeyer, 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, M.D.
state: Maryland
city: Ann Arbor
country: United States
facility: Daniela Minecan, M.D.
state: Michigan
city: Flint
country: United States
facility: George Zureikat, M.D.
state: Michigan
city: Columbia
country: United States
facility: Pradeep Sahota, M.D.
state: Missouri
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: New Brunswick
country: United States
facility: Sushmita Mikkilineni, 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: Charlotte
country: United States
facility: James Lee, M.D.
state: North Carolina
city: Cincinnati
country: United States
facility: Raouf Amin, MD
state: Ohio
city: Cincinnati
country: United States
facility: Martin Scharf, Ph.D.
state: Ohio
city: Dublin
country: United States
facility: Markus H. Schmidt, M.D., Ph.D.
state: Ohio
city: Toledo
country: United States
facility: Michael Neeb, Ph.D.
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: Eugene
country: United States
facility: Dainis Irbe, M.D.
state: Oregon
city: Allentown
country: United States
facility: William Pistone, M.D.
state: Pennsylvania
city: Bethlehem
country: United States
facility: Jeffery Gould, M.D.
state: Pennsylvania
city: Clairton
country: United States
facility: Guillermo Borrero, M.D.
state: Pennsylvania
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: James M. Ferguson, M.D.
state: Utah
city: Seattle
country: United States
facility: Ralph A. Pascualy, M.D.
state: Washington
city: Calgary
country: Canada
facility: Adam Moscovitch, M.D.
state: Alberta
city: Scarborough
country: Canada
facility: Leonid Kayumov, M.D.
state: Ontario
city: Toronto
country: Canada
facility: Mortimer Mamelak, M.D.
state: Ontario
city: Windsor
country: Canada
facility: Allen Denys, M.D.
state: Ontario
Study officials:
References: