A Study in Healthy Male Volunteers to Investigate a New Drug for the Treatment of Parkinson's Disease
Primary Purpose
Parkinson's Disease
Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
V81444
Sponsored by
About this trial
This is an interventional basic science trial for Parkinson's Disease
Eligibility Criteria
Inclusion Criteria:
- Healthy male volunteers: aged 25 to 55 years, in good general health as determined by medical history, physical examination and screening investigations, and taking no regular medication.
- Confirmation to be sought for all volunteers that their general practitioner has provided an acceptable medical history.
Exclusion Criteria:
- Any significant medical condition or a history of such a condition that the Investigator considers should exclude the subject from the study.
Specific exclusion criteria relate to
- usual caffeine intake and willingness to abstain from caffeine
- history or evidence of clinically significant gastro-intestinal disease
- presence of structural brain abnormality
- contraindications or cautions for MRI scanning
- clotting test results
- exposure to significant levels of ionising radiation in the past
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
V81444
Arm Description
Single oral dose of V81444
Outcomes
Primary Outcome Measures
Plasma concentration V81444 corresponding with 50% brain A2A receptor occupancy.
Plasma concentrations of V81444 and binding of [11C]SCH442416 radioligand to brain A2A receptors using PET before and after V81444 dosing to determine occupancy of A2A receptors by V81444.
Secondary Outcome Measures
Cognitive function using functional MRI
Change versus placebo in proportion of subjects with adverse events
Change versus placebo in proportion of subjects with abnormal laboratory findings
Change versus placebo in proportion of subjects with clinically significant abnormalities on vital signs
Change versus placebo in proportion of subjects with clinically significant abnormalities in 12-lead ECG
Change versus placebo in proportion of subjects with clinically significant abnormalities on physical examination
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02764892
Brief Title
A Study in Healthy Male Volunteers to Investigate a New Drug for the Treatment of Parkinson's Disease
Official Title
An Open Label Study of V81444 Using Positron Emission Tomography to Assess Occupancy of Brain Adenosine A2A Receptors & Functional & Perfusion MRI to Explore Effects on Regional Brain Activity & Perfusion in Healthy Male Volunteers
Study Type
Interventional
2. Study Status
Record Verification Date
May 2016
Overall Recruitment Status
Completed
Study Start Date
August 2012 (undefined)
Primary Completion Date
November 2012 (Actual)
Study Completion Date
March 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Vernalis (R&D) Ltd
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The main purpose of the study is to identify the best dose of V81444 to use in future trials in patients with Parkinson's disease. The study will also explore the effects of V81444 on brain activity and blood flow with tests of mental ability ("cognitive function tests"). It will also check how safe V81444 is and how well it is tolerated after dosing.
Detailed Description
In this Phase I, single-centre, open-label, adaptive, single-dose study at multiple dose levels, the relationship between dose and plasma concentration of orally administered V81444 to brain A2A RO was investigated in 6 healthy male volunteers. In addition, the effects of V81444 on regional brain activity and perfusion during tests of cognitive function, and the safety and tolerability of V81444 were assessed. For each subject, the study consisted of a screening visit, a baseline visit, a treatment period, and a safety follow-up visit. The dose of V81444 and timing of scans performed were defined in the protocol for the first 2 subjects only. The dose, nature and timings of assessments for subsequent subjects were determined based on review of emerging receptor binding, pharmacokinetic (PK), pharmacodynamic (PD) and safety information.
In each treatment period, subjects were admitted to the unit on the day before dosing (Day -1), received a single oral dose of V81444 on Day 1 and, subject to satisfactory medical review, were discharged a minimum of 12 h after dosing. Overall, 3 doses of V81444 were assessed (250 mg, 50 mg, and 100 mg), with 2 subjects included at each dose level. PD assessments were performed at baseline and after each dose of V81444 using PET (with the A2A radioligand, to measure brain A2A RO, as well as MRI techniques to investigate the effects of V81444 on regional brain activity and perfusion during cognitive function tests. PK parameters were assessed by assay of V81444 concentration in plasma. Safety and tolerability were assessed by monitoring physical examination findings, adverse events (AEs), vital signs, 12 lead electrocardiogram (ECG) and clinical laboratory safety tests.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Parkinson's Disease
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
6 (Actual)
8. Arms, Groups, and Interventions
Arm Title
V81444
Arm Type
Experimental
Arm Description
Single oral dose of V81444
Intervention Type
Drug
Intervention Name(s)
V81444
Intervention Description
Single oral dose of V81444
Primary Outcome Measure Information:
Title
Plasma concentration V81444 corresponding with 50% brain A2A receptor occupancy.
Description
Plasma concentrations of V81444 and binding of [11C]SCH442416 radioligand to brain A2A receptors using PET before and after V81444 dosing to determine occupancy of A2A receptors by V81444.
Time Frame
Up to 27 hours after a single dose
Secondary Outcome Measure Information:
Title
Cognitive function using functional MRI
Time Frame
5 hours after dosing
Title
Change versus placebo in proportion of subjects with adverse events
Time Frame
Up to 7 Days after last dose
Title
Change versus placebo in proportion of subjects with abnormal laboratory findings
Time Frame
Up to 7 Days after last dose
Title
Change versus placebo in proportion of subjects with clinically significant abnormalities on vital signs
Time Frame
Up to 7 Days after last dose
Title
Change versus placebo in proportion of subjects with clinically significant abnormalities in 12-lead ECG
Time Frame
Up to 7 Days after last dose
Title
Change versus placebo in proportion of subjects with clinically significant abnormalities on physical examination
Time Frame
Up to 7 Days after last dose
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
25 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Healthy male volunteers: aged 25 to 55 years, in good general health as determined by medical history, physical examination and screening investigations, and taking no regular medication.
Confirmation to be sought for all volunteers that their general practitioner has provided an acceptable medical history.
Exclusion Criteria:
Any significant medical condition or a history of such a condition that the Investigator considers should exclude the subject from the study.
Specific exclusion criteria relate to
usual caffeine intake and willingness to abstain from caffeine
history or evidence of clinically significant gastro-intestinal disease
presence of structural brain abnormality
contraindications or cautions for MRI scanning
clotting test results
exposure to significant levels of ionising radiation in the past
12. IPD Sharing Statement
Learn more about this trial
A Study in Healthy Male Volunteers to Investigate a New Drug for the Treatment of Parkinson's Disease
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