E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Cataplexy in patients with narcolepsy |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028713 |
E.1.2 | Term | Narcolepsy |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10048322 |
E.1.2 | Term | Narcolepsy aggravated |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10021235 |
E.1.2 | Term | Idiopathic narcolepsy |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10007737 |
E.1.2 | Term | Cataplexy |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10048323 |
E.1.2 | Term | Cataplexy aggravated |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Evaluate and compare the efficacy and safety of escalating doses of BF2.649 and BF2.649 add on Modafinil on cataplexy attacks. |
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E.2.2 | Secondary objectives of the trial |
Evaluate the additive/synergistic effect of the combination of BF2.649 and Modafinil on excessive daytime sleepiness (EDS), on vigilance/attention, and on changes in disease severity assessed by investigators in patients with narcolepsy. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Males and females of any ethnic origin, 18 years old and over. 2. De novo patients i.e. with newly diagnosed narcolepsy and cataplexy and not taking any treatment for EDS and cataplexy. Patients with previously diagnosed narcolepsy and cataplexy and not taking any treatment for EDS and cataplexy for more than 3 months 3. Partial or total cataplexy attacks with a frequency of at least 5 per week during a 14-day baseline period and Epworth Sleepiness Scale (ESS) score ≥ 14/24 at the end of baseline period (V2). 4. The patient has expressed a willingness to participate in and complete the study, and signed and dated informed consent prior to beginning protocol required procedures. 5. Women must be surgically sterile or 2 years postmenopausal. Females of child-bearing potential must use a medically accepted effective method of birth control. These women must use oral contraceptives containing at least 0.05 mg Ethinyl estradiol since the effectiveness of steroidal contraceptives may be reduced when used with Modafinil. The steroidal contraceptives at micro and mini doses should be excluded. Patients should agree to continue this method for the duration of the study and for one month after thediscontinuation of Modafinil treatment. Women should be negative to serum pregnancy test performed at the screening visit. Females should not be breast-feeding patient. 6. In the opinion of the investigator, the patient must have adequate support to comply with the entire study requirements as described in the protocol (e.g., transportation to and from trial site, self rating scales and diaries completion, drug compliance, scheduled visits, tests). 7. Patients should be warned that change in tratment as a consequence of inclusion in this study may reduce their ability to drive as well as his / her impaired ability to operate machinery. If indicated by investigator, the patient must be willing to not operate a car or heavy machinery for the duration of the trial or as long as the investigator deems clinically indicated. In addition, the patient should be willing to maintain during the study their usual behaviours which could affect their diurnal sleepiness (e.g., circadian rhythm, caffeine consumption, nocturnal sleep duration). |
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E.4 | Principal exclusion criteria |
1. The use of BF2.649 or any previous investigational drugs within 30-day period prior to initial screening visit (V1) for this trial. 2. Patients who are unable or unwilling to temporarily discontinue non authorized drugs or substances. 3. Current or recent (within one year) history of a substance abuse or dependence disorder including alcohol abuse as defined in Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). 4. Any significant abnormality in the physical examination or clinical laboratory results (e.g. liver or kidney function deficiency). 5. Patients with severe depression (BDI≥16) or with suicidal risk (item G BDI > 0). 6. Any significant serious abnormality of the cardiovascular illness e.g. recent myocardial infarction, angina, hypertension or dysrhythmias (within the prior 6 months), Electrocardiogram Bazett’s corrected QT interval (QT x root from [HR/60]) strickly higher than 450 ms, history of left ventricular hypertrophy or mitral valve prolapse. 7. Patients with Severe hepatic Impairment (e.g. prothrombin ratio < 50% or factor V < 50% for patients receiving anti-vitamin K medication) or with Severe Renal Impairment (e.g. serum creatine greater than 2.0 mg/dl), or with any other significant abnormality in the physical examination or clinical laboratory results. 8. Psychiatric and neurological disorders, such as moderate or severe psychosis or dementia, bipolar illness, severe anxiety, clinical depression, history of seizure disorder or other problem that in the investigator’s opinion would preclude the patient’s participation and completion of this trial or comprise reliable representation of subjective symptoms. 9. Prior severe adverse reactions to CNS stimulants. 10. Known hypersensitivity to the tested treatment including active substance and inactive excipients. 11. Other active clinically significant illness, including unstable cardiovascular, endocrine, neoplastic, gastrointestinal, hematologic, hepatic, immunologic, metabolic, neurological (other than narcolepsy/cataplexy), pulmonary, and/or renal disease which could interfere with the study conduct or counter-indicate the study treatments or place the patient at risk during the trial or compromise the study objectives. 12. Any patients presenting congenital galactosemia, glucose-galactose malabsorption or lactase deficiency due to the presence of lactose in investigational treatments. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary measure of efficacy is the change from baseline in weekly cataplexy attacks. Frequency of cataplexy attacks is collected daily by reporting the number of total and partial cataplexy attacks in patient’s daily sleep diary. The number of weekly cataplexy attacks will be evaluated at baseline and at endpoint corresponding to the end of 8-week double-blind phase or to the time of the last on-study visit for any subject who withdraws prior to study completion.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Information not present in EudraCT |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | Information not present in EudraCT |
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.8.4.1 | Number of sites anticipated in Member State concerned | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 27 |
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 | No |
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 visit of the last subject undergoing the trial. |
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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 | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 10 |