Dose finding phase IIb study of Bavisant to evaluate its safety and efficacy in treatment of excessive daytime sleepiness (EDS) in parkinson’s Disease (PD).

INTERVENTION: Product Name: Bavisant Product Code: JNJ‐31001074 Pharmaceutical Form: Tablet INN or Proposed INN: Bavisant dihydrochloride monohydrate Other descriptive name: BAVISANT HYDROCHLORIDE MONOHYDRATE Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 0.5‐ Pharmaceutical form of the placebo: Tablet Route of administration of the placebo: Oral use Product Name: Bavisant Product Code: JNJ‐31001074 Pharmaceutical Form: Tablet INN or Proposed INN: Bavisant dihydrochloride monohydrate Other descriptive name: BAVISANT HYDROCHLORIDE MONOHYDRATE Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 1‐ Pharmaceutical form of the placebo: Tablet Route of administration of the placebo: Oral use Product Name: Bavisant Product Code: JNJ‐31001074 Pharmaceutical Form: Tablet INN or Proposed INN: Bavisant dihydrochloride monohydrate Other descriptive name: BAVISANT HYDROCHLORIDE MONOHYDRATE Concentration unit: millilitre(s)/gram Concentration type: equal Concentration number: 3‐ Pharmaceutical form of the placebo: Tablet Route of administration of the placebo: Oral use CONDITION: Excessive daytime sleepiness with Parkinson's Disease ; MedDRA version: 20.0 Level: PT Classification code 10061536 Term: Parkinson's disease System Organ Class: 10029205 ‐ Nervous system disorders Therapeutic area: Diseases [C] ‐ Nervous System Diseases [C10] PRIMARY OUTCOME: Main Objective: To assess the efficacy of Bavisant compared to placebo after a 6‐week treatment period on the excessive daytime sleepiness in Parkinson's disease. Primary end point(s): The primary endpoint will be the mean absolute change of treatment groups in the Epworth Sleepiness Scale (ESS) from baseline to the end of the 6‐week treatment period, assessed as both the intragroup change compared to baseline and intergroup change compared to placebo. Secondary Objective: To assess the efficacy and safety assessment of Bavisant compared to placebo after 2 weeks and 6 weeks of treatment. The efficacy assessment will include excessive daytime sleepiness, motor control, and depression. Timepoint(s) of evaluation of this end point: From baseline to the end of the 6‐week treatment period. SECONDARY OUTCOME: Secondary end point(s): Efficacy in Excessive Daytime Sleepiness (EDS):; • Mean absolute change in the Epworth Sleepiness Scale (ESS) from baseline to the end of the 2‐week treatment period.; • ESS clinical response, defined as ESS absolute decrease from baseline of at least 3.0 points, after 2 and 6 weeks of treatment.; • ESS clinical response, defined as ESS = 10 after 2 and 6 weeks of treatment.; • ESS clinical response, defined as either ESS = 10 after 2 and 6 weeks of treatment or ESS absolute decrease from baseline of at least 3.0 points after 2 and 6 weeks of treatment. ; • Mean relative change in the Epworth Sleepiness Scale (ESS) from baseline to the end of the 2‐week and 6‐week treatment periods (percentage of absolute decrease compared to baseline ESS).; • Mean absolute change in the Scales for Outcome in Parkinson’s Disease Sleep (SCOPA‐ Sleep) from baseline to the end of the 2‐week and 6‐week treatment period.; • Mean absolute change in the Parkinson's Disease Sleep Scale (PDSS‐2) from baseline to the end of the 2‐week and 6‐week treatment period.; • Mean absolute change in the Maintenance of Wakefulness Test (MWT) from baseline to the end of the 6‐week treatment period.; • Mean absolute change in the polysomnography from baseline to the end of the 6‐week treatment period.; Efficacy in Parkinson's disease (PD):; • Mean absolute change in the MDS‐UDPRS scale Part III (motor control) from baseline to the end of the 2‐week and 6‐week treatment period.; • Mean absolute change in the depression BDI‐II score from screening/baseline to the end of the 6‐week treatment period.; The safety of Bavisant compared to placebo will be assessed by the evaluation of the following:; • Incidence of Adverse Events (AEs), Serious Adverse Events (SAEs), and Adverse Events of Special Interest (AESIs) as headache, nausea and insomnia; • Incidence of physical examination, vital signs and laboratory tests findings (haematology and biochemistry); • Incidence of cardiovascular safety findings (blood pressure, heart rate, ECG including QT/QTc); • Incidence of slit lamp examination findings Timepoint(s) of evaluation of this end point: From baseline to the end of the 6‐week treatment period. INCLUSION CRITERIA: (1) Signed informed consent (no study‐related procedures may be performed before the subject has signed the consent form). (2) Subjects of either sex aged 50 to 80 years (both inclusive and relative to Day 1). (3) Subjects with previous diagnosis of Parkinson's disease (following the UK Parkinson’s disease society brain bank clinical diagnostic criteria). (4) Subjects capable of understanding and complying with protocol requirements. (5) Subjects with medical history of excessive daytime sleepiness. (6) Subjects with moderate or severe excessive daytime sleepiness indicated by an Epworth Sleepiness Score (ESS) > 12 at screening . (7) Subjects with stable nocturnal sleep hygiene practices (e.g. temperature, darkness, quiet, place to lie down and stretch out) as per investigator's judgement. (8) Male subjects who are nonsterilized and sexually active with a female partner of childbearing potential agree to use adequate contraception from signi