CVXL-0107 a glutamate release inhibitor, has shown evidence of antiparkinsonian and antidyskinetic activity in a macaque model and has shown a significant effect on the UPDRS-III (Movement Disorder Society - Unified Parkinson's Disease Rating Scale) while "ON", as well as an increase of "ON-time" without dyskinesia or without troublesome dyskinesia in a previous phase 2a proof of concept study. This study will confirm the efficacy of CVXL-0107 in combination with optimal dose of levodopa on motor symptoms of Parkinson's disease (PD) .
Phase IIa study, 1:1 randomized, double blind placebo- controlled, with cross-over. Each volunteer patient will be randomly assigned to receive CVXL-0107 or placebo as add-on PD therapy and crossed-over to the other arm in the second sequence of the study. They will be assessed during an acute levodopa challenge test with one intake of the study drug or placebo with a supra-optimal dose of levodopa after 2 weeks of daily treatment with the same study drug or placebo. Patients will be cross-overed to the other treatment and reassessed during a second acute levodopa challenge test after 2 weeks of daily treatment with the study drug or the placebo. The study will evaluate the anti-PD and the anti-dyskinesia efficacy of CVXL-0107 as measured by MDS-UPDRS part III (Movement Disorder Society - Unified Parkinson's Disease Rating Scale) and on levodopa-induced dyskinesia as measured by the AIMS (Abnormal Involuntary Movement Scale).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
21
Clevexel Pharma
Maisons-Alfort, France
Change in MDS-UPDRS part III (Movement Disorder Society - Unified Parkinson's Disease Rating Scale Part III) score.
CVXL-0107 and placebo
Time frame: at visit 3 (day 15= challenge test day) and visit 4 (day 37= challenge test day): at baseline (before L-Dopa administration), then every 20 minutes during the first hour and then every 30 minutes during 5 hours.
Change in AIMS ( Abnormal Involuntary Movement Scale) score
CVXL-0107 and placebo
Time frame: at visit 3 (day 15= challenge test day) and visit 4 (day 37 = challenge test day): at baseline (before L-Dopa administration), then every 20 minutes during the first hour and then every 30 minutes during 5 hours
Incidence of Clinical Treatment-Emergent Adverse Events [Safety and Tolerability]
Physical examination, vital signs
Time frame: at visit 3 (day 14) and visit 4 (day 36)
Hematology laboratory safety of CVXL-0107
complete blood count
Time frame: at visit 3 (day 14) and visit 4 (day 36)
Hepatic laboratory safety of CVXL-0107
aspartate transaminase, alanine transaminase, gamma-glutamyl-transpeptidase, alkaline phosphatase
Time frame: at visit 3 (day 14) and visit 4 (day 36)
Area Under the Curve [AUC] of CVXL-0107 concentrations
Blood samples at L-dopa intake and after 20', 40', 60', 90', 120', 240'.
Time frame: at visit 3 (day 15= challenge test day) and visit 4 (day 37= challenge test day)
Area Under the Curve [AUC] of levodopa concentrations
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Blood samples at L-dopa intake and after 20', 40', 60', 90', 120', 240'.
Time frame: at visit 3 (day 15= challenge test day) and visit 4 (day 37= challenge test day)
Assessment of total daily "ON" time in Patients Diaries
Total "ON-time"
Time frame: During 3 days, prior to visit 3 (days 11-13) and prior to visit 4 (days 33, 34, 35)
Assessment of daily "ON" time without dyskinesia in Patients Diaries
"ON-time" without dyskinesia
Time frame: During 3 days; prior to visit 3 (days 11-13) and prior to visit 4 (days 33, 34, 35)