CASPAR: BEN-2001 in Parkinson Disease Patients With Excessive Daytime Sleepiness

• Sponsor: BenevolentAI Bio (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03194217
• Collaborator: (none)
• Enrollment: 244
• Location: 1
• Arms: 4
• Actual Duration (Months): 18.5
• Patients Per Site Per Month: 13.2

Study Details

Study Description

Brief Summary

This phase 2b study is designed as multicentre, multinational, randomized, double blind, parallel group and placebo controlled with three doses of Bavisant (0.5, 1, and 3 mg/d) in subjects with excessive daytime sleepiness with Parkinson's disease.

Condition or Disease	Intervention/Treatment	Phase
Excessive Daytime Sleepiness; Parkinson Disease	Drug: BEN-2001; Drug: Placebo	Phase 2

Detailed Description

Phase 2b study will be conducted with the aim of investigating the efficacy and safety of three fixed doses of Bavisant (0.5, 1 and 3 mg/d) compared to placebo for the treatment of excessive daytime sleepiness (EDS) in subjects with Parkinson's disease.

Study Design

• Study Type: Interventional
• Actual Enrollment: 244 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official 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).
• Actual Study Start Date: Nov 10, 2017
• Actual Primary Completion Date: May 28, 2019
• Actual Study Completion Date: May 28, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: BEN-2001, 0.5mg Experimental treatment	Drug: BEN-2001; Bavisant dihydrochloride monohydrate for oral use; Other Names: Bavisant
Placebo Comparator: Placebo Placebo comparator	Drug: Placebo; Placebo
Experimental: BEN-2001, 1.0mg Experimental treatment	Drug: BEN-2001; Bavisant dihydrochloride monohydrate for oral use; Other Names: Bavisant
Experimental: BEN-2001, 3.0mg Experimental treatment	Drug: BEN-2001; Bavisant dihydrochloride monohydrate for oral use; Other Names: Bavisant

Outcome Measures

Primary Outcome Measures

1. Measurement of Sleepiness Using the Epworth Sleepiness Scale (ESS) at Baseline and Post Dose. [6 weeks]

   Mean absolute change of Bavisant treatment groups in the Epworth Sleepiness Scale (ESS) from baseline to the end of the 6-week treatment period. The ESS score (sum of 8 item scores) ranges from 0 to 24 with higher score corresponding to higher average sleep propensity in daily life (higher daytime sleepiness). Eligibility determined based on ESS score of 13 and above.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subjects of either sex aged 50 to 80 years Subjects with previous diagnosis of Parkinson's disease (following the UK Parkinson's disease society brain bank clinical diagnostic criteria)

• Subjects capable of understanding and complying with protocol requirements

• Subjects with medical history of excessive daytime sleepiness

Exclusion Criteria:

• Subjects with excessive daytime sleepiness due to conditions other than Parkinson's disease (including narcolepsy)

• Subjects with clinical evidence of depression with significant psychiatric comorbidities (Hamilton Rating Scale for Depression - HAM-D score greater than or equal to 17; with or without treatment)

• Subjects with evidence of significant fatigue (Fatigue Severity Scale - FSS greater than or equal to 36

• Subjects with known history of abuse of alcohol or other addictive substances in the 6 months prior to inclusion.

• Subjects with known allergies or hypersensitivity to Bavisant or any of its excipients.

• Subjects who are pregnant or lactating.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	MaxBlue Institute	Miami	Florida	United States	33018

Sponsors and Collaborators

• BenevolentAI Bio

Investigators

• Principal Investigator: William G Ondo, M.D, Methodist Neurological Institute

Study Documents (Full-Text)

• Study Protocol - Nov 7, 2018
• Statistical Analysis Plan - Oct 25, 2018

More Information

Publications

None provided.

• Responsible Party: BenevolentAI Bio
• ClinicalTrials.gov Identifier: NCT03194217
• Other Study ID Numbers: BB-2001-201b
• First Posted: Jun 21, 2017
• Last Update Posted: Nov 24, 2020
• Last Verified: Jul 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Parkinson Disease; Disorders of Excessive Somnolence; Sleepiness

Study Results

Participant Flow

Arm/Group Title	Placebo	BEN-2001, 0.5mg	BEN-2001, 1.0mg	BEN-2001, 3.0mg
Arm/Group Description	Placebo comparator Placebo: Placebo	Experimental treatment BEN-2001: Bavisant dihydrochloride monohydrate for oral use	Experimental treatment BEN-2001: Bavisant dihydrochloride monohydrate for oral use	Experimental treatment BEN-2001: Bavisant dihydrochloride monohydrate for oral use
Period Title: Overall Study
STARTED	60	60	60	64
COMPLETED	60	57	56	60
NOT COMPLETED	0	3	4	4

Baseline Characteristics

Arm/Group Title	Placebo	BEN-2001, 0.5mg	BEN-2001, 1.0mg	BEN-2001, 3.0mg	Total
Arm/Group Description	Placebo comparator Placebo: Placebo	Experimental treatment BEN-2001: Bavisant dihydrochloride monohydrate for oral use	Experimental treatment BEN-2001: Bavisant dihydrochloride monohydrate for oral use	Experimental treatment BEN-2001: Bavisant dihydrochloride monohydrate for oral use	Total of all reporting groups
Overall Participants	60	60	60	64	244
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	18 30%	21 35%	18 30%	27 42.2%	84 34.4%
>=65 years	42 70%	39 65%	42 70%	37 57.8%	160 65.6%
Sex: Female, Male (Count of Participants)
Female	21 35%	23 38.3%	17 28.3%	20 31.3%	81 33.2%
Male	39 65%	37 61.7%	43 71.7%	44 68.8%	163 66.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	2 3.3%	0 0%	0 0%	2 0.8%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	1 1.7%	1 1.7%	0 0%	0 0%	2 0.8%
White	59 98.3%	57 95%	59 98.3%	64 100%	239 98%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	1 1.7%	0 0%	1 0.4%
Region of Enrollment (participants) [Number]
United States	13 21.7%	12 20%	11 18.3%	11 17.2%	47 19.3%
Europe	47 78.3%	48 80%	49 81.7%	53 82.8%	197 80.7%

Outcome Measures

1. Primary Outcome

Title	Measurement of Sleepiness Using the Epworth Sleepiness Scale (ESS) at Baseline and Post Dose.
Description	Mean absolute change of Bavisant treatment groups in the Epworth Sleepiness Scale (ESS) from baseline to the end of the 6-week treatment period. The ESS score (sum of 8 item scores) ranges from 0 to 24 with higher score corresponding to higher average sleep propensity in daily life (higher daytime sleepiness). Eligibility determined based on ESS score of 13 and above.
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Placebo	BEN-2001, 0.5mg	BEN-2001, 1.0mg	BEN-2001, 3.0mg
Arm/Group Description	Placebo comparator Placebo: Placebo	Experimental treatment BEN-2001: Bavisant dihydrochloride monohydrate for oral use	Experimental treatment BEN-2001: Bavisant dihydrochloride monohydrate for oral use	Experimental treatment BEN-2001: Bavisant dihydrochloride monohydrate for oral use
Measure Participants	60	60	60	64
Least Squares Mean (Standard Error) [units on a scale]	-4.34 (0.5)	-4.64 (0.51)	-3.46 (0.51)	-4.73 (0.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BEN-2001, 0.5mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.668
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.30
	Confidence Interval	(2-Sided) 95%; -1.68 to 1.08
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.70
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	BEN-2001, 1.0mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.213
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.88
	Confidence Interval	(2-Sided) 95%; -0.50 to 2.26
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.70
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	BEN-2001, 3.0mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.575
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.39
	Confidence Interval	(2-Sided) 95%; -1.76 to 0.98
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.70
	Estimation Comments

Adverse Events

Time Frame	70 days
Arm/Group Title	Placebo		BEN-2001, 0.5mg		BEN-2001, 1.0mg		BEN-2001, 3.0mg
Arm/Group Description	Placebo comparator Placebo: Placebo		Experimental treatment BEN-2001: Bavisant dihydrochloride monohydrate for oral use		Experimental treatment BEN-2001: Bavisant dihydrochloride monohydrate for oral use		Experimental treatment BEN-2001: Bavisant dihydrochloride monohydrate for oral use
All Cause Mortality
	Placebo		BEN-2001, 0.5mg		BEN-2001, 1.0mg		BEN-2001, 3.0mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/60 (0%)		0/60 (0%)		0/60 (0%)		0/64 (0%)
Serious Adverse Events
	Placebo		BEN-2001, 0.5mg		BEN-2001, 1.0mg		BEN-2001, 3.0mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/60 (1.7%)		0/60 (0%)		0/60 (0%)		2/64 (3.1%)
Gastrointestinal disorders
Constipation	0/60 (0%)	0	0/60 (0%)	0	0/60 (0%)	0	1/64 (1.6%)	1
Musculoskeletal and connective tissue disorders
Muscular weakness	0/60 (0%)	0	0/60 (0%)	0	0/60 (0%)	0	1/64 (1.6%)	1
Surgical and medical procedures
cholecystectomy	1/60 (1.7%)	1	0/60 (0%)	0	0/60 (0%)	0	0/64 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo		BEN-2001, 0.5mg		BEN-2001, 1.0mg		BEN-2001, 3.0mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/60 (18.3%)		16/60 (26.7%)		27/60 (45%)		26/64 (40.6%)
Eye disorders
Cataract Nuclear	0/60 (0%)		0/60 (0%)		2/60 (3.3%)		0/64 (0%)
Gastrointestinal disorders
Diarrhoea	0/60 (0%)		0/60 (0%)		2/60 (3.3%)		0/64 (0%)
Constipation	0/60 (0%)		0/60 (0%)		1/60 (1.7%)		2/64 (3.1%)
Abdominal Pain Upper	0/60 (0%)		2/60 (3.3%)		0/60 (0%)		0/64 (0%)
Nausea	1/60 (1.7%)		2/60 (3.3%)		4/60 (6.7%)		3/64 (4.7%)
Dry Mouth	0/60 (0%)		1/60 (1.7%)		2/60 (3.3%)		0/64 (0%)
General disorders
Fatigue	0/60 (0%)		1/60 (1.7%)		2/60 (3.3%)		1/64 (1.6%)
Infections and infestations
Nasopharygitis	3/60 (5%)		2/60 (3.3%)		1/60 (1.7%)		1/64 (1.6%)
Influenza	0/60 (0%)		0/60 (0%)		2/60 (3.3%)		0/64 (0%)
Investigations
Triglycerous increase	1/60 (1.7%)		1/60 (1.7%)		3/60 (5%)		0/64 (0%)
Musculoskeletal and connective tissue disorders
Back pain	1/60 (1.7%)		1/60 (1.7%)		1/60 (1.7%)		2/64 (3.1%)
Nervous system disorders
Head ache	0/60 (0%)		1/60 (1.7%)		2/60 (3.3%)		1/64 (1.6%)
Tremor	0/60 (0%)		0/60 (0%)		0/60 (0%)		2/64 (3.1%)
Somnolence	1/60 (1.7%)		0/60 (0%)		1/60 (1.7%)		2/64 (3.1%)
Psychiatric disorders
Initial Insomnia	2/60 (3.3%)		3/60 (5%)		1/60 (1.7%)		3/64 (4.7%)
Insomnia	0/60 (0%)		0/60 (0%)		0/60 (0%)		3/64 (4.7%)
Middle Insomnia	0/60 (0%)		0/60 (0%)		2/60 (3.3%)		3/64 (4.7%)
Nightmare	0/60 (0%)		1/60 (1.7%)		0/60 (0%)		2/64 (3.1%)
Skin and subcutaneous tissue disorders
Hyperhydrosis	2/60 (3.3%)		1/60 (1.7%)		1/60 (1.7%)		1/64 (1.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.