E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Excessive sleepiness associated with Narcolepsy or Obstructive Sleep Apnea/Hypopnea Syndrome. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 7.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10015595 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the safety and tolerability of treatment with Provigil in children and adolescents with excessive sleepiness (ES) associates with narcolepsy or obstructive sleep apnea/hypopnea syndrome (OSAHS), when administered for up to 6 months. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the long term effectiveness of Provigil in children and adolescents with excessive sleepiness (ES) associates with narcolepsy or obstructive sleep apnea/hypopnea syndrome (OSAHS), when administered for up to 6 months. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
(a) written informed consent/assent is obtained (b) a boy or girl aged 6 to 16 years, inclusive (c) 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) or OSAHSORhave a previous diagnosis of narcolepsy or OSAHS within 2 years of the screening visit (d) have a complaint of ES (e) are in good health as determined by a medical and psychiatric history, physical examination, ECG, and clinical laboratory tests (f) 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 (g) 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 (h) able to swallow a tablet similar in size and shape to the study drug tablet (i) 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 (j) have a parent or legal representative who is willing to participate in the study |
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E.4 | Principal exclusion criteria |
(a) have self-induced sleep deprivation/poor sleep hygiene (b) 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 (c) have a history of suicide attempt, or are at suicidal risk (d) a clinically significant drug sensitivity to stimulants such as amfetamine, dexamfetamine, or methylphenidate; and/or modafinil or any of its components (e) 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 if the patient has been on a stable dose for at least 1 month.) (f) received any investigational drug (except modafinil) within 4 weeks of the baseline visit (g) any disorder that could interfere with drug absorption, distribution, metabolism, or excretion (including previous gastrointestinal surgery) (h) active, clinically significant gastrointestinal, cardiovascular, hepatic, renal, hematologic, neoplastic, endocrine, neurologic, immunodeficiency, pulmonary, or other major clinically significant disorder/disease (i) 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 (j) 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.) (k) seated pulse outside the range of 60 to 115 bpm after resting for 5 minutes (l) 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 (m) a total daily intake of more than 500 mg of caffeine per day (eg, approximately ten 330-mL cans of caffeinated soft drinks, 5 cups of coffee or tea, or about 750 g of chocolate per day) within 1 week of the baseline visit (n) pregnant or lactating/nursing girl; any girl who becomes pregnant during the study will be withdrawn (o) a clinically significant illness within 4 weeks of the baseline visit; or is symptomatic for any clinically significant illness at the baseline visit |
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety: - clinical laboratory tests at all postbaseline visits - physical examinations at months 3, and 6, or early termination - vital signs at all postbaseline visits - body weight and height (using a height measuring stick) at all monthly visits (months 1 – 6) - 12-lead ECGs at months 3, and 6, or early termination - CBCL/6-18 at months 3, and 6, or early termination
Efficacy: - the CGI-S ratings (for severity of ES) at months 3,and 6, or last postbaseline observation - the PDSS at months 3, and 6, or last postbaseline observation |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Last patient completing follow up period |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 12 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 12 |