This is a Phase 2b study investigating the efficacy and safety of mesdopetam as adjunct therapy on daily ON-time without troublesome dyskinesia in patients with Parkinson disease. Mesdopetam is taken for 84 days.
At the screening visit consenting patients will be screened for eligibility according to study specific inclusion/exclusion criteria within 8 weeks before start of Investigational Medicinal Product (IMP) administration. A diary concordance training will be performed and following the screening visit the patient will be asked to self-administer three 24-hour home diaries and to bring the completed diaries to the baseline visit for assessment prior randomization. At the baseline visit, patients will be randomized to receive one of three doses of mesdopetam (dose 1, dose 2 and dose 3) or placebo b.i.d. During the first week a dose run-in phase will take place, where all patients allocated to mesdopetam will receive a run-in dose of mesdopetam twice daily and patients allocated to placebo will receive placebo twice daily. At Visit 2, patients will receive mesdopetam dose 1, dose 2 or dose 3 or placebo b.i.d., as randomized and continue the same dose for the rest of the treatment period until end of treatment (EOT). Dose reductions are restricted and the dose can only be reduced once. Dose reductions are permitted from visit 2 (day 9) until visit 3 (day 28), where after the dose should be kept stable until EOT. The treatment allocation will be double-blind, i.e. it will not be disclosed to the patients, the site staff or the Sponsor. During the treatment period, changes in disease state and ON phase dyskinesia will be assessed using the Movement Disorder Society revised Unified Parkinson's Disease Rating Scale (MDS-UPDRS), the modified Unified Dyskinesia Rating Scale (UDysRS), i.e. parts 1, 3 and 4, and Clinician's Global Impression of Severity (CGI-S). Furthermore, patients will self-administer three 24-hour home diaries prior to visit 3 (week 4), visit 4 (week 8) and visit 5 (week 12) to assess daily motor function. Blood samples for pharmacokinetic (PK) analysis will be collected at visit 4 (week 8) and visit 5 (week 12). Visit 6 (follow-up) will be performed for all patients, including any patients that discontinue the IMP early, 5-8 days after last administration of IMP.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
155
Oral use
Oral use
Change in Average Daily Hours of ON-time Without Troublesome Dyskinesia With Mesdopetam Compared to Placebo as Assessed With 24-hour Patient Home Diaries From Baseline to End of Treatment.
This is a self-administered diary where patients assess their motor state every half hour during 24 hours. ON time without troublesome dyskinesia measures time when the medication is working without causing troublesome dyskinesia.
Time frame: Baseline to end of treatment (week 12)
Change From Baseline in Mean Score of ON-phase Dyskinesia Assessed With the Sum Score of the Modified Unified Dyskinesia Rating Scale (UDysRS), Parts 1, 3 and 4, With Mesdopetam Compared to Placebo.
The scoring range is 0-88, where higher score means more dyskinesia.
Time frame: Baseline to end of treatment (week 12)
Change From Baseline in Mean Score of Disability Associated With ON-phase Dyskinesia Assessed With the Sum Score of Parts 1b and 4 of the Unified Dyskinesia Rating Scale (UDysRS), With Mesdopetam Compared to Placebo.
The scoring range is 0-60, where higher score means more disability associated with dyskinesia.
Time frame: Baseline to end of treatment (week 12)
Change From Baseline in Mean Score of Motor Symptoms of PD Assessed With MDS-UPDRS Total Score of Part 2 (M-EDL) (With Mesdopetam Compared to Placebo)
This scale is a patient reported outcome measure assessing motor aspects of experiences of daily living. Minimum score is 0 and maximum score is 52. A higher score means more Parkinson's disease motor symptoms.
Time frame: Baseline to end of treatment (week 12)
Change From Baseline in Average Daily Hours of OFF-time (With Mesdopetam Compared to Placebo).
This is a self-administered diary where patients assess their motor state every half hour during 24 hours. OFF time means time means daily time spent when the medication is not working.
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Movement Disorders Center of Arizona
Scottsdale, Arizona, United States
Collaborative Neuroscience Research (CNS Research)
Long Beach, California, United States
Parkinson's Disease and Movement Disorders Center of Silicon Valley
Palo Alto, California, United States
Colorado Springs Neurological Associates
Colorado Springs, Colorado, United States
Parkinson's Disease and Movement Disorders Center of Boca Raton
Boca Raton, Florida, United States
Avantis Clinical Research
Miami, Florida, United States
Elias Research Associates (Allied Biomedical Research Institute)
Miami, Florida, United States
Pharmax Research of South Florida, Inc.
Miami, Florida, United States
Life Medical Research Group Corp
Miami Gardens, Florida, United States
NeuroStudies.net, LLC
Decatur, Georgia, United States
...and 34 more locations
Time frame: Baseline to end of treatment (week 12)