A Clinical Study of Mesdopetam in Patients With Parkinson's Disease Experiencing Levodopa Induced Dyskinesia

A Randomized, Double-blind, Placebo-controlled Phase IIB Study Evaluating the Efficacy of Mesdopetam on Daily ON-time Without Troublesome Dyskinesia in Patients With Parkinson's Disease

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.

Study Overview

• Status: Completed
• Conditions: Parkinson Disease
• Intervention / Treatment: Drug: Placebo; Drug: Mesdopetam

Detailed Description

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
• Enrollment (Actual): 155
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Lille, France, 59037
    • Centre Hospitalier Régional Universitaire de Lille
  • Limoges, France, 87042
    • CHU Dupuytren 1 - Neurologie
  • Nimes, France, 30029
    • CHU Caremeau
  • Poitiers, France, 86021
    • CHU De Poitiers
  • Rennes, France, 35033
    • CHU Rennes-Pontchaillou
  • Rouen, France, 76031
    • CHU Charles Nicolle; Service de Neurologie
• Israel
  • Haifa, Israel, 3109601
    • Rambam Health Care Campus, Department of Neurology
  • Jerusalem, Israel, 9112001
    • Hadassah University Hospital-Ein Kerem, Department of Neurology
  • Petah Tikva, Israel, 4941492
    • Rabin Medical Centre - Beilinson Hospital, Department of Neurology
  • Ramat Gan, Israel, 5265601
    • The Chaim Sheba Medical Centre, Department of Neurology
  • Tel Aviv, Israel, 6423906
    • Tel Aviv Sourasky Medical Centre; Movement Disorders Unit
• Italy
  • Genova, Italy, 16132
    • IRCCS - Ospedale "San Martino"
  • Padova, Italy, 35128
    • Azienda Ospedaliera di Padova
  • Roma, Italy, 00163
    • IRCCS San Raffaele Pisana
  • Roma, Italy, 00168
    • Fondazione Policlinico Gemelli IRCCS
  • Salerno, Italy, 84131
    • AOU San Giovanni di Dio e Ruggi d'Aragona, Clinica Neurologica
• Poland
  • Bydgoszcz, Poland, 85-163
    • Centrum Medyczne Neuromed
  • Katowice, Poland, 40-097
    • Specjalistyczna Praktyka Lekarska
  • Kraków, Poland, 30-363
    • Centrum Medyczne Plejady
  • Kraków, Poland, 30-539
    • Specjalistyczne Gabinety Sp z o.o.
  • Kraków, Poland, 31-505
    • Krakowska Akademia Neurologii
  • Oświęcim, Poland, 32-600
    • Instytut Zdrowia
  • Siemianowice Śląskie, Poland, 41-100
    • Neuro-Care
  • Warsaw, Poland, 02-042
    • Next Stage sp.z o.o.
  • Warszawa, Poland, 01-684
    • Centrum Medyczne NeuroProtect
  • Zabrze, Poland, 41-807
    • Clinhouse Centrum Medyczne
• Serbia
  • Belgrade, Serbia, 11000
    • Clinical Hospital Center Zvezdara, Clinical department of Neurology
  • Belgrade, Serbia, 11000
    • University Clinical Center of Serbia, Clinic for neurology
  • Kragujevac, Serbia, 34000
    • University Clinical Center Kragujevac, Clinic for Neurology (Site 601)
  • Kragujevac, Serbia, 34000
    • University Clinical Center Kragujevac, Clinic for Neurology (Site 602)
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Movement Disorders Center of Arizona
  • California
    • Long Beach, California, United States, 90806
      • Collaborative Neuroscience Research (CNS Research)
    • Palo Alto, California, United States, 94301
      • Parkinson's Disease and Movement Disorders Center of Silicon Valley
  • Colorado
    • Colorado Springs, Colorado, United States, 80907
      • Colorado Springs Neurological Associates
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Parkinson's Disease and Movement Disorders Center of Boca Raton
    • Miami, Florida, United States, 33155
      • Avantis Clinical Research
    • Miami, Florida, United States, 33155
      • Elias Research Associates (Allied Biomedical Research Institute)
    • Miami, Florida, United States, 33175
      • Pharmax Research of South Florida, Inc.
    • Miami Gardens, Florida, United States, 33014
      • Life Medical Research Group Corp
  • Georgia
    • Decatur, Georgia, United States, 30030
      • NeuroStudies.net, LLC
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky, Department of Neurology
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74136
      • The Movement Disorder Clinic of Oklahoma
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center
  • Washington
    • Spokane, Washington, United States, 99202
      • Inland Northwest Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female ≥30 and ≤79 years of age at the time of screening.
2. Signed a current Ethics Committee approved informed consent form (ICF).
3. PD, per UK Parkinson's Disease Society (UKPDS) Brain Bank Clinical Diagnostic Criteria.
4. Minimal amount of 2 hours of levodopa-induced daily "ON-time with troublesome dyskinesia" during waking hours
5. Functional impact of dyskinesias determined as a score of ≥2 as per Question 4.2 of the MDS-UPDRS.
6. On a stable regimen of antiparkinson medications for at least 30 days prior to first home diary completion which must include a levodopa preparation administered 3-8 times/day (excluding nighttime levodopa) and willing to continue the same doses and regimens during study participation. Rescue medications such as Madopar dispersable and Apomorphine injections are allowed if prescribed PRN prior to study entry.
7. Any other current and allowed prescription/non-prescription medications and/or nutritional supplements taken regularly must have been at a stable dose and regimen for at least 30 days prior to first home diary completion and the patient must be willing to continue the same doses and regimens during study participation (this criterion does not apply to medications that are being taken pre-study only on an as-needed basis).
8. Able to complete 24-hour patient home diaries of which two valid diaries must be presented at visit 1.

Exclusion Criteria:

1. History of neurosurgical intervention related to PD (e.g. deep brain stimulation).
2. Treatment with pump delivered antiparkinsonian therapy (i.e. subcutaneous apomorphine or levodopa/carbidopa intestinal infusion).
3. History of seizures within two years prior to screening.
4. History of stroke or transient ischemic attack (TIA) within two years prior to screening.
5. History of cancer within five years prior to screening, with the following exceptions: adequately treated non-melanomatous skin cancers, localized bladder cancer, non metastatic prostate cancer or in situ cervical cancer.
6. Presence of cognitive impairment, as evidenced by a Mini-Mental State Examination (MMSE) score of less than 24 during screening.
7. A Hoehn and Yahr stage of 5.
8. Ongoing treatment with amantadine at time of screening or within 6 weeks prior first home diary completion.
9. Treatment with Inbrija (levodopa inhalation powder) at time of screening or within 4 weeks prior first home diary completion.
10. Any history of a significant heart condition or cardiac arrhythmias within the past 5 years, any repolarisation deficits or any other clinically significant abnormal ECG as judged by the Investigator.
11. Severe or ongoing unstable medical condition including a history of poorly controlled diabetes; obesity associated with metabolic syndrome; uncontrolled hypertension; cerebrovascular disease, or any form of clinically significant cardiac disease, clinically significant symptomatic orthostatic hypotension (a fall and/or a discomfort); clinically significant hepatic disease, severe renal impairment, i.e. creatinine clearance <30 mL/min (stage IV or V).
12. Any history of a neurological disorder other than PD or a psychiatric disorder, including history of Diagnostic and Statistical Manual of Mental Disorders (DSM) IV diagnosed major depression or psychosis. Patients with illusions or hallucinations with no loss of insight will be eligible. Patients with mild depression who are well controlled on a stable dose of an antidepressant medication for at least 4 weeks before screening will be eligible.
13. Enrolment in any other clinical study involving medication, medical devices or surgical procedures, current or within three months prior to screening visit, or previous participation in the present study. Patients enrolled in non-interventional clinical trials will be eligible.
14. Drug and/or alcohol abuse.
15. History of severe drug allergy or hypersensitivity.
16. If female, is pregnant or lactating, or has a positive pregnancy test result pre-dose.
17. Patients unwilling to use two forms of contraception (one of which being a barrier method (see Section 8.1) during the treatment period and 90 days for men and 30 days for women after last IMP dose.
18. Any planned major surgery within the duration of the study.
19. Any other condition or symptoms preventing the patient from entering the study, according to the Investigator's judgement.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mesdopetam dose 1; Mesdopetam capsule (mg), dose 1, 1 capsule b.i.d. for 84 days.	Drug: Mesdopetam; Oral use; Other Names: IRL790
Experimental: Mesdopetam dose 2; Mesdopetam capsule (mg), dose 2, 1 capsule b.i.d. for 84 days.	Drug: Mesdopetam; Oral use; Other Names: IRL790
Experimental: Mesdopetam dose 3; Mesdopetam capsule (mg), dose 3, 1 capsule b.i.d. for 84 days.	Drug: Mesdopetam; Oral use; Other Names: IRL790
Placebo Comparator: Placebo; Placebo capsule, 1 capsule b.i.d. for 84 days	Drug: Placebo; Oral use

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline to end of treatment (week 12)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	Baseline to end of treatment (week 12)

Collaborators and Investigators

• Sponsor: Integrative Research Laboratories AB
• Investigators: Study Director: Joakim Tedroff, Integrative Research Laboratories AB (IRLAB)

Publications and helpful links

General Publications

• Becanovic K, Vittoria de Donno M, Sousa VC, Tedroff J, Svenningsson P. Effects of a Novel Psychomotor Stabilizer, IRL790, on Biochemical Measures of Synaptic Markers and Neurotransmission. J Pharmacol Exp Ther. 2020 Jul;374(1):126-133. doi: 10.1124/jpet.119.264754. Epub 2020 May 1.
• Waters S, Sonesson C, Svensson P, Tedroff J, Carta M, Ljung E, Gunnergren J, Edling M, Svanberg B, Fagerberg A, Kullingsjo J, Hjorth S, Waters N. Preclinical Pharmacology of [2-(3-Fluoro-5-Methanesulfonyl-phenoxy)Ethyl](Propyl)amine (IRL790), a Novel Dopamine Transmission Modulator for the Treatment of Motor and Psychiatric Complications in Parkinson Disease. J Pharmacol Exp Ther. 2020 Jul;374(1):113-125. doi: 10.1124/jpet.119.264226. Epub 2020 May 1.
• Svenningsson P, Johansson A, Nyholm D, Tsitsi P, Hansson F, Sonesson C, Tedroff J. Safety and tolerability of IRL790 in Parkinson's disease with levodopa-induced dyskinesia-a phase 1b trial. NPJ Parkinsons Dis. 2018 Dec 6;4:35. doi: 10.1038/s41531-018-0071-3. eCollection 2018.

Study record dates

Study Major Dates

• Study Start (Actual): October 29, 2020
• Primary Completion (Actual): December 2, 2022
• Study Completion (Actual): December 9, 2022

Study Registration Dates

• First Submitted: June 15, 2020
• First Submitted That Met QC Criteria: June 15, 2020
• First Posted (Actual): June 17, 2020

Study Record Updates

• Last Update Posted (Estimated): March 6, 2024
• Last Update Submitted That Met QC Criteria: February 9, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Dyskinesias; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Dopamine Agents; Dopamine Antagonists; Mesdopetam
• Other Study ID Numbers: IRL790C005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No