Prospective, randomized, double-blind study, parallel-group, multi-center trial assessing the effects of escalating doses of BF2.649 and BF2.649 add on Modafinil on cataplexy in patients with narcolepsy (HARMONY II) - Harmony II

INTERVENTION: Product Code: BF 2.649 Pharmaceutical Form: Capsule* Current Sponsor code: BF2.649 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 10‐ Pharmaceutical form of the placebo: Capsule* Route of administration of the placebo: Oral use Product Code: BF 2.649 Pharmaceutical Form: Capsule* Current Sponsor code: BF2.649 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 20‐ Pharmaceutical form of the placebo: Capsule* Route of administration of the placebo: Oral use Product Code: BF 2.649 Pharmaceutical Form: Capsule* Current Sponsor code: BF2.649 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 40‐ Pharmaceutical form of the placebo: Capsule* Route of administration of the placebo: Oral use Trade Name: Modiodal Product Name: Modafinil Product Code: N06BA07 Pharmaceutical Form: Capsule* INN or Proposed INN: Modafinil Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 100‐ Pharmaceutical form of the placebo: Capsule* Route of administration of the placebo: Oral use CONDITION: Cataplexy in patients with narcolepsy ; MedDRA version: 9.1 Level: LLT Classification code 10028713 Term: Narcolepsy ; MedDRA version: 9.1 Level: LLT Classification code 10048322 Term: Narcolepsy aggravated ; MedDRA version: 9.1 Level: LLT Classification code 10021235 Term: Idiopathic narcolepsy ; MedDRA version: 9.1 Level: LLT Classification code 10007737 Term: Cataplexy ; MedDRA version: 9.1 Level: LLT Classification code 10048323 Term: Cataplexy aggravated PRIMARY OUTCOME: Main Objective: Evaluate and compare the efficacy and safety of escalating doses of BF2.649 and BF2.649 add on Modafinil on cataplexy attacks. 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.; Secondary Objective: 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. 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