Clinical Trials Register

Summary
EudraCT Number:	2017-000877-35
Sponsor's Protocol Code Number:	BB-2001-201b
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2017-07-17
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

UK - MHRA

A.2

EudraCT number

2017-000877-35

A.3

Full title of the trial

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).

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

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.

A.3.2

Name or abbreviated title of the trial where available

Treatment of excessive daytime sleepiness with Bavisant in Parkinson’s Disease Patients (CASPAR)

A.4.1

Sponsor's protocol code number

BB-2001-201b

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	BenevolentAI Bio
B.1.3.4	Country	United Kingdom
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	BenevolentAI Bio
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	BenevolentAI Bio
B.5.2	Functional name of contact point	Adepeju Oshisanya
B.5.3	Address:
B.5.3.1	Street Address	40 Churchway
B.5.3.2	Town/ city	London
B.5.3.3	Post code	W1 1LW
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+44203096 0737
B.5.6	E-mail	adepeju.oshisanya@benevolent.ai

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Bavisant
D.3.2	Product code	JNJ-31001074
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Bavisant dihydrochloride monohydrate
D.3.9.3	Other descriptive name	BAVISANT HYDROCHLORIDE MONOHYDRATE
D.3.9.4	EV Substance Code	SUB30870
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.5
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Bavisant
D.3.2	Product code	JNJ-31001074
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Bavisant dihydrochloride monohydrate
D.3.9.3	Other descriptive name	BAVISANT HYDROCHLORIDE MONOHYDRATE
D.3.9.4	EV Substance Code	SUB30870
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 3
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Bavisant
D.3.2	Product code	JNJ-31001074
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Bavisant dihydrochloride monohydrate
D.3.9.3	Other descriptive name	BAVISANT HYDROCHLORIDE MONOHYDRATE
D.3.9.4	EV Substance Code	SUB30870
D.3.10	Strength
D.3.10.1	Concentration unit	millilitre(s)/gram
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	3
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Excessive daytime sleepiness with Parkinson's Disease

E.1.1.1

Medical condition in easily understood language

Parkinson's Disease

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10061536
E.1.2	Term	Parkinson's disease
E.1.2	System Organ Class	10029205 - Nervous system disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To assess the efficacy of Bavisant compared to placebo after a 6-week treatment period on the excessive daytime sleepiness in Parkinson's disease.

E.2.2

Secondary objectives of the trial

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.

E.2.3

Trial contains a sub-study

E.3

Principal 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.

E.4

Principal 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 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 ≥ 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) Subejcts 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 employee(s), or is an immediate family member (ie, spouse, parent, child, sibling) of a study site employee(s) involved in conduct of this study.

E.5 End points

E.5.1

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.

E.5.1.1

Timepoint(s) of evaluation of this end point

From baseline to the end of the 6-week treatment period.

E.5.2

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 HAM-D score from screening/baseline to the end of the 6-week treatment period.
• 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) 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 slit lamp examination findings

E.5.2.1

Timepoint(s) of evaluation of this end point

From baseline to the end of the 6-week treatment period.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

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

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

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

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

Czech Republic

Germany

Italy

Poland

Spain

United Kingdom

United States

E.8.7

Trial has a data monitoring committee

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

LVLS

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

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

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

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

210

F.4.2.2

In the whole clinical trial

240

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

All subjects will perform a Follow-up visit 28 days after last IMP administration and the End of Study Visit to check their health or followup on Adverse Events. Subjects will return to standard treatment after the end of the study

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2017-07-25

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-08-08

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2019-05-28

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials