Assess the Safety and Effectiveness of PROVIGIL Treatment in Children and Adolescents With Excessive Sleepiness

Condition(s) targeted: Excessive Daytime Sleepiness; Narcolepsy

Intervention: PROVIGIL (modafinil) (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: Cephalon

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 obstructive sleep apnea/hypopnea syndrome (OSAHS), when administered for up to 6 months.

Official title: A 6-Month Open Label, Flexible-Dosage Study to Assess the Safety and Effectiveness of PROVIGIL (Modafinil) Treatment in Children and Adolescents With Excessive Sleepiness Associated With Narcolepsy or Obstructive Sleep Apnea/Hypopnea Syndrome

Study design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety Study

Primary outcome: Evaluate the safety and tolerability of treatment with PROVIGIL in children and adolescents with excessive daytime sleepiness associated with narcolepsy and obstructive sleep apnea/hypopnea syndrome, when administered for up to 6 months.

Secondary outcome: Evaluate long-term effective by using: the clinical global impression of change (CGI-C) ratings for severity of ES and total score from the Pediatric Daytime Sleepiness Scale (PDSS).

Minimum age: 6 Years. Maximum age: 16 Years. Gender(s): Both.

Criteria:

Inclusions Criteria:

- written informed consent/assent is obtained

- meet 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) or OSAHS OR have a previous diagnosis of narcolepsy or OSAHS before the screening visit

- have a complaint of ES

- 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 on the National High Blood Pressure Education Program guidelines for blood pressure levels for boys and girls ages 6 to 16 years

- girls who are postmenarche or sexually active, have a negative urine pregnancy test at

screening, 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 2 cycles after participation in the study); acceptable methods of birth control include: barrier method with spermicide; steroidal contraceptives (oral, transdermal, implanted, or injected) in conjunction with a barrier method; intrauterine device (IUD); or abstinence

- able to swallow a tablet similar in size and shape to the study drug tablet

- negative urine drug screen (UDS) for any illicit drug, alcohol (ethanol), stimulants

at screening; if positive for stimulants (prescribed for excessive sleepiness) at screening, UDS to be repeated after a washout period and before baseline

- have a parent or legal representative who is willing to participate in the study

Exclusion Criteria: Patients are excluded for participating in this if 1 or more of the following criteria are met:

- have self-induced sleep deprivation/poor sleep hygiene

- have a past or present seizure disorder (except history of 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 amfetamine,

dexamfetamine, or methylphenidate; and/or modafinil or any of its components

- use of any monoamine oxidase (MAO) inhibitors or selective serotonin reuptake

inhibitors (SSRIs) within 2 weeks of the baseline visit (NOTE: SSRIs will be allowed for cataplexy if the patient has been on a stable dose for atleast 1 month.)

- 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) at the screening or baseline visit

- absolute neutrophil count (ANC) below the lower limit of normal at screening (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 to 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 500mg of caffeine per day (eg, approximately ten

330-ml cans of caffeinated soft drinks, 5 cups of coffee or tea, or about 750g 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 baseline visit

Princess Margaret Children's H, Perth WA 6100, Australia

Charles University, Prague 12800, Czech Republic

Rinnekoti Research Center, Espoo FI 02980, Finland

University of Oulu, Oulu, Finland

Sleep Research Unit Dentalia, Turku, Finland

University of Kuopio, Kuopio, Finland

CHU Grenoble, Grenoble 38043, France

Hopital Robert Debre, Paris 75019, France

Dana Children's Hospital, Tel Aviv 64239, Israel

Pediatric Sleep Clinic, Beer Sheva, Israel

Meyer Children's Hospital, Haifa 31096, Israel

Centro per lo Studio del Sonno, Troina 94018, Italy

Centro per ldisturbi del sonno, Milano 20017, Italy

Clinica Pediatrica, Roma 0189, Italy

Centro per lo Studio, Bologna 40123, Italy

Centro Del Sonno, Roma 0185, Italy

Centro di Chirurgia, Milan 20126, Italy

Centro Medical de Especialidad, Monterrey 64060, Mexico

Hosp. Reg. del ISSSTE-Puebla, Puebla, Mexico

Instituto Nacional, Mexico City D.F. 06720, Mexico

Instituto Nacional, Mexico City D.F. 14000, Mexico

Hospital General de Mexico, Mexico City D.F. 06720, Mexico

Hosp Gen Univ Gregorio Maranon, Madrid 28007, Spain

Instituto Universitario Dexeus, Barcelona 08017, Spain

Servicio de Neurofisiologia, Granada 18014, Spain

Hospital Son Dureta, Palma de Mallorca 07014, Spain

Clinica Quiron, Valencia 46609, Spain

Hospital La Paz, Madrid 28046, Spain

CHU Hopital Roger Salengro, Lille, Cedex 59037, France

Hopital Guy de Chauliac, Montpellier, Cedex 05 34295, France

Hopital Debrousse, Lyon, Cedex 05 69322, France

Park Hospital for Children, Headington, Oxford OX37LQ, United Kingdom

Last updated: April 20, 2006