Study of PROVIGIL ® (Modafinil) Treatment in Children and Adolescents With Excessive Sleepiness Associated With Obstructive Sleep Apnea/Hypopnea Syndrome

Sleep Apnea, Obstructive Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00107809
• Other study ID #: C1538/3028/AP/MN-OSAHS
• Status: Completed
• Phase: Phase 3
• First received: April 8, 2005
• Last updated: May 8, 2014
• Start date: October 2004
• Est. completion date: September 2005

Study information

• Verified date: May 2014
• Source: Teva Pharmaceutical Industries
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationHealth Canada:
• Study type: Interventional

Clinical Trial 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).

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 140
• Est. completion date: September 2005
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 6 Years to 16 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Apnea
• Disorders of Excessive Somnolence
• Sleep Apnea Syndromes
• Sleep Apnea, Obstructive

Intervention

Drug:
• Modafinil

Locations

Country	Name	City	State
Canada	Adam Moscovitch, M.D.	Calgary	Alberta
Canada	Leonid Kayumov, M.D.	Scarborough	Ontario
Canada	Mortimer Mamelak, M.D.	Toronto	Ontario
Canada	Allen Denys, M.D.	Windsor	Ontario
United States	William Pistone, M.D.	Allentown	Pennsylvania
United States	Daniela Minecan, M.D.	Ann Arbor	Michigan
United States	D. Alan Lankford, Ph.D.	Atlanta	Georgia
United States	Gary Montgomery, M.D.	Atlanta	Georgia
United States	Jerry Silverboard, M.D.	Atlanta	Georgia
United States	John Hudson, M.D.	Austin	Texas
United States	Jeffery Gould, M.D.	Bethlehem	Pennsylvania
United States	Robert Doekel, Jr., M.D.	Birmingham	Alabama
United States	James Lee, M.D.	Charlotte	North Carolina
United States	Helene A. Emsellem, M.D.	Chevy Chase	Maryland
United States	Michael Kohrman, M.D.	Chicago	Illinois
United States	Stephen H. Sheldon, D.O., FAAP	Chicago	Illinois
United States	Martin Scharf, Ph.D.	Cincinnati	Ohio
United States	Raouf Amin, MD	Cincinnati	Ohio
United States	Guillermo Borrero, M.D.	Clairton	Pennsylvania
United States	Pradeep Sahota, M.D.	Columbia	Missouri
United States	Richard Bogan, M.D., FCCP	Columbia	South Carolina
United States	David Sperry, M.D.	Dallas	Texas
United States	James Cook, M.D.	Danville	Indiana
United States	Markus H. Schmidt, M.D., Ph.D.	Dublin	Ohio
United States	Dainis Irbe, M.D.	Eugene	Oregon
United States	George Zureikat, M.D.	Flint	Michigan
United States	Joseph McCarty, M.D.	Fort Smith	Arkansas
United States	Marc Raphaelson, M.D.	Frederick	Maryland
United States	Todd J. Swick, M.D.	Houston	Texas
United States	Julie Thompson-Dobkin, D.O.	Huntington Beach	California
United States	John L. Carroll, M.D.	Little Rock	Arkansas
United States	Mark Buchfuhrer, M.D.	Long Beach	California
United States	Yury Furman, M.D.	Los Angeles	California
United States	Karen Waters, M.D.	Louisville	Kentucky
United States	Anna Ivanenko, M.D., Ph.D.	Maywood	Illinois
United States	Amerigo Padilla, M.D.	Miami	Florida
United States	Julie Jacques, D.O.	Morristown	Tennessee
United States	Kathleen Ryan, M.D.	Mount Laurel	New Jersey
United States	Martin A. Cohn, M.D.	Naples	Florida
United States	Sushmita Mikkilineni, M.D.	New Brunswick	New Jersey
United States	Gary Zammit, M.D.	New York	New York
United States	Monroe Karetzky, M.D.	Newark	New Jersey
United States	Henry Lahmeyer, M.D.	Northfield	Illinois
United States	Jorg Pahl, M.D.	Oklahoma City	Oklahoma
United States	William C. Orr, Ph.D.	Oklahoma City	Oklahoma
United States	Stuart Menn, M.D.	Palm Springs	California
United States	Richard Shubin, M.D.	Pasadena	California
United States	Lee Brooks, M.D.	Princeton	New Jersey
United States	Judith Owens, M.D., MPH	Providence	Rhode Island
United States	William Torch, M.D., MS	Reno	Nevada
United States	Lawrence Sher, M.D.	Rolling Hills Estates	California
United States	James M. Ferguson, M.D.	Salt Lake City	Utah
United States	Jerry J. Tomasovic, M.D.	San Antonio	Texas
United States	Milton K. Erman, M.D.	San Diego	California
United States	Stephen Brooks, M.D.	San Francisco	California
United States	Paul Haberman, M.D.	Santa Monica	California
United States	Ralph A. Pascualy, M.D.	Seattle	Washington
United States	Margaret Ann Springer, M.D.	Shreveport	Louisiana
United States	Jed Black, M.D.	Stanford	California
United States	Michael Neeb, Ph.D.	Toledo	Ohio
United States	William Leeds, D.O.	Topeka	Kansas
United States	Marc Seelagy, M.D.	Trenton	New Jersey
United States	Derek Loewy, Ph.D.	Tucson	Arizona
United States	Stuart Quan, M.D.	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Cephalon

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	The Clinical Global Impression of Change (CGI-C) ratings for ES, at the last post baseline observation (week 6 or early termination)
Secondary	The Clinical Global Impression of Change (CGI-C) ratings for severity of ES
Secondary	The total score from the Pediatric Daytime Sleepiness Scale (PDSS)