A phase IIb, randomized, double blind, parallel group, placebo control, multicentre, 6-week dose-finding study to assess the efficacy and safety of Bavisant for the treatment of excessive daytime sleepiness in subjects with Parkinson's disease.

• Register: EUCTR
• Last refreshed on: 30 June 2019
• Main ID: EUCTR2017-000877-35-CZ
• Date of registration: 05/06/2017
• Prospective Registration: Yes
• Primary sponsor: BenevolentAI Bio
• Public title: A phase IIb, randomized, double blind, parallel group, placebo control, multicentre, 6-week dose-finding study to assess the efficacy and safety of Bavisant for the treatment of excessive daytime sleepiness in subjects with Parkinson's disease.
• Scientific title: 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). - Treatment of excessive daytime sleepiness with Bavisant in Parkinson’s Disease Patients (CASPAR)
• Date of first enrolment: 09/08/2017
• Target sample size: 240
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-000877-35
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 4
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Czech Republic, Germany, Italy, Poland, Spain, United Kingdom, United States

Contacts

• Name: Adepeju Oshisanya
• Affiliation: BenevolentAI Bio

• Name: Adepeju Oshisanya
• Affiliation: BenevolentAI Bio

Key inclusion & exclusion criteria

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)* of minimum 3 months before informed consent date.
(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 is nonsterilized and sexually active with a female partner of childbearing potential who agrees to use adequate contraception from signing of informed consent throughout the duration of the study and for 4 weeks after last dose
(9) Female subjects of childbearing potential who are sexually active with a nonsterilized male partner agrees to use routinely adequate contraception from signing of informed consent throughout the duration of the study and for 4 weeks after last dose
(10) Subjects on stable permitted concomitant medication for at least 4 weeks before screening.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 120
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 120

Exclusion criteria:
(1) Subjects with excessive daytime sleepiness due to conditions other than Parkinson's disease (including narcolepsy)
(2) Subjects with significant eye disease which may substantially impact the subject's mobility and ability to have eye examination conducted as per investigator's judgement.
(3) Subjects with a recent history of suicide attempt (defined as an active, interrupted or aborted attempt within the past 1 year), or reports suicidal ideation in the past 3 months as indicated by a positive response on the C-SSRS at screening visit (an answer of ‘yes’ to any of the 6 questions)
(4) Subjects with clinical evidence of depression with significant psychiatric comorbidities (Hamilton Rating Scale for Depression – HAM-D score = 17; with or without treatment)
(5) Subjects with evidence of significant Cognitive Impairment (Montreal Cognitive Assessment - MoCA score = 22 at screening)
(6) Subjects with evidence of significant fatigue (Fatigue Severity Scale - FSS = 36)
(7) Subjects with high risk of sleep apnoea (Berlin questionnaire with = 2 categories where the score is positive)
(8) Subjects taking any of the following prohibited medications at screening:
• Alerting agents, including r-modafinil, modafinil or methylphenidate
• Benzodiazepines
• Histamine active agents
• Hypnotics
• Cholinergics
• Skeletal muscle relaxants
• Clozapine
• Atomoxetine
• Amitriptyline
• Any other daytime medications which affect sleep
(9) Subjects with chronic oral and / or ophthalmic steroidal use
(10) Subjects with either renal or hepatic impairment defined by laboratory parameters >1.5x age-adjusted limits of normal range
• Hepatic damage: Alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase, or total bilirubin
• Renal damage: Blood creatinine, blood urea nitrogen [BUN], or estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73m2
(11) Subjects with abnormal ECG time intervals at baseline including QTc (> 450 for males and > 470 for females)
(12) Subjects with known history of lung malignancy.
(13) Subjects with known history of abuse of alcohol or other addictive substances in the 6 months prior to inclusion.
(14) Subjects with known allergies or hypersensitivity to Bavisant or any of its excipients.
(15) Subjects who are pregnant or lactating.
(16) Subjects who do not wish to or cannot comply with study procedures.
(17) Subjects currently receiving, or having received within 3 months prior to enrolment into this clinical study, any investigational drug.
(18) Subjects who are study-site employees, or are immediate family members (i.e., spouse, parent, child, sibling) of a study site employee involved in conduct of this study.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

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]

Intervention(s)

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: mg milligram(s)
Concentration type: equal
Concentration number: 3-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

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.

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.

Timepoint(s) of evaluation of this end point: From baseline to the end of the 6-week treatment period.

Secondary Outcome(s)

Secondary end point(s): • 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 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 HAM-D score from screening/baseline to the end of the the 2-week and 6-week treatment period and safety follow-up.
• Mean absolute change in the Montreal Cognitive Assessment – MoCA score from screening/baseline to the end of the 6-week treatment period.
• Mean absolute change in the Fatigue Severity Scale – FSS 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) such as headache, nausea and insomnia
• Incidence of suicidal ideation (C-SSRS) findings from screening/baseline to the end of the 2-week and the 6-week treatment period and safety follow-up
• Incidence of positive psychotic symptoms (BPRS+) findings from screening/baseline to the end of the 2-week and the 6-week treatment period and safety follow-up
• 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 eye exam findings

Timepoint(s) of evaluation of this end point: From baseline to the end of the 6-week treatment period.

Secondary ID(s)

BB-2001-201b

Source(s) of Monetary Support

BenevolentAI Bio

Ethics review

Status: Approved
Approval date:
Contact: