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

NCT04435431 | Completed Phase 2 Results FDA Drug

• 1 other identifier: IRL790C005
• Study Type: interventional
• Target: 155
• Locations: 6 countries
• Sites: 44

Brief Summary

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.

Conditions

Parkinson Disease

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• 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.

  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.

  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)

  Baseline to end of treatment (week 12)

• Change From Baseline in Average Daily Hours of OFF-time (With Mesdopetam Compared to Placebo).

  Baseline to end of treatment (week 12)

Study Arms (4)

Mesdopetam dose 1

EXPERIMENTAL

Mesdopetam capsule (mg), dose 1, 1 capsule b.i.d. for 84 days.

Drug: Mesdopetam

Mesdopetam dose 2

EXPERIMENTAL

Mesdopetam capsule (mg), dose 2, 1 capsule b.i.d. for 84 days.

Drug: Mesdopetam

Mesdopetam dose 3

EXPERIMENTAL

Mesdopetam capsule (mg), dose 3, 1 capsule b.i.d. for 84 days.

Drug: Mesdopetam

Placebo

PLACEBO COMPARATOR

Placebo capsule, 1 capsule b.i.d. for 84 days

Drug: Placebo

Interventions

Mesdopetam DRUG

Oral use

Also known as: IRL790

Mesdopetam dose 1; Mesdopetam dose 2; Mesdopetam dose 3

Placebo DRUG

Oral use

Placebo

Eligibility Criteria

• Age: 30 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female ≥30 and ≤79 years of age at the time of screening.
• Signed a current Ethics Committee approved informed consent form (ICF).
• PD, per UK Parkinson's Disease Society (UKPDS) Brain Bank Clinical Diagnostic Criteria.
• Minimal amount of 2 hours of levodopa-induced daily "ON-time with troublesome dyskinesia" during waking hours
• Functional impact of dyskinesias determined as a score of ≥2 as per Question 4.2 of the MDS-UPDRS.
• 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.
• 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).
• Able to complete 24-hour patient home diaries of which two valid diaries must be presented at visit 1.

You may not qualify if:

• History of neurosurgical intervention related to PD (e.g. deep brain stimulation).
• Treatment with pump delivered antiparkinsonian therapy (i.e. subcutaneous apomorphine or levodopa/carbidopa intestinal infusion).
• History of seizures within two years prior to screening.
• History of stroke or transient ischemic attack (TIA) within two years prior to screening.
• 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.
• Presence of cognitive impairment, as evidenced by a Mini-Mental State Examination (MMSE) score of less than 24 during screening.
• A Hoehn and Yahr stage of 5.
• Ongoing treatment with amantadine at time of screening or within 6 weeks prior first home diary completion.
• Treatment with Inbrija (levodopa inhalation powder) at time of screening or within 4 weeks prior first home diary completion.
• 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.
• 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).
• 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.
• 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.
• Drug and/or alcohol abuse.
• History of severe drug allergy or hypersensitivity.

Sponsors & Collaborators

• Integrative Research Laboratories AB: lead

Study Sites (44)

Movement Disorders Center of Arizona

Scottsdale, Arizona, 85258, United States

Location

Collaborative Neuroscience Research (CNS Research)

Long Beach, California, 90806, United States

Location

Parkinson's Disease and Movement Disorders Center of Silicon Valley

Palo Alto, California, 94301, United States

Location

Colorado Springs Neurological Associates

Colorado Springs, Colorado, 80907, United States

Location

Parkinson's Disease and Movement Disorders Center of Boca Raton

Boca Raton, Florida, 33486, United States

Location

Avantis Clinical Research

Miami, Florida, 33155, United States

Location

Elias Research Associates (Allied Biomedical Research Institute)

Miami, Florida, 33155, United States

Location

Pharmax Research of South Florida, Inc.

Miami, Florida, 33175, United States

Location

Life Medical Research Group Corp

Miami Gardens, Florida, 33014, United States

Location

NeuroStudies.net, LLC

Decatur, Georgia, 30030, United States

Location

University of Kentucky, Department of Neurology

Lexington, Kentucky, 40536, United States

Location

The Movement Disorder Clinic of Oklahoma

Tulsa, Oklahoma, 74136, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Inland Northwest Research

Spokane, Washington, 99202, United States

Location

Centre Hospitalier Regional Universitaire de Lille

Lille, 59037, France

Location

CHU Dupuytren 1 - Neurologie

Limoges, 87042, France

Location

CHU Carémeau

Nîmes, 30029, France

Location

CHU de Poitiers

Poitiers, 86021, France

Location

CHU Rennes-Pontchaillou

Rennes, 35033, France

Location

CHU Charles Nicolle; Service de Neurologie

Rouen, 76031, France

Location

Rambam Health Care Campus, Department of Neurology

Haifa, 3109601, Israel

Location

Hadassah University Hospital-Ein Kerem, Department of Neurology

Jerusalem, 9112001, Israel

Location

Rabin Medical Centre - Beilinson Hospital, Department of Neurology

Petah Tikva, 4941492, Israel

Location

The Chaim Sheba Medical Centre, Department of Neurology

Ramat Gan, 5265601, Israel

Location

Tel Aviv Sourasky Medical Centre; Movement Disorders Unit

Tel Aviv, 6423906, Israel

Location

IRCCS - Ospedale "San Martino"

Genova, 16132, Italy

Location

Azienda Ospedaliera di Padova

Padua, 35128, Italy

Location

IRCCS San Raffaele Pisana

Roma, 00163, Italy

Location

Fondazione Policlinico Gemelli IRCCS

Roma, 00168, Italy

Location

AOU San Giovanni di Dio e Ruggi d'Aragona, Clinica Neurologica

Salerno, 84131, Italy

Location

Centrum Medyczne Neuromed

Bydgoszcz, 85-163, Poland

Location

Specjalistyczna Praktyka Lekarska

Katowice, 40-097, Poland

Location

Centrum Medyczne PLEJADY

Krakow, 30-363, Poland

Location

Specjalistyczne Gabinety Sp z o.o.

Krakow, 30-539, Poland

Location

Krakowska Akademia Neurologii

Krakow, 31-505, Poland

Location

Instytut Zdrowia

Oświęcim, 32-600, Poland

Location

Neuro-Care

Siemianowice Śląskie, 41-100, Poland

Location

Centrum Medyczne NeuroProtect

Warsaw, 01-684, Poland

Location

Next Stage sp.z o.o.

Warsaw, 02-042, Poland

Location

ClinHouse Centrum Medyczne

Zabrze, 41-807, Poland

Location

Clinical Hospital Center Zvezdara, Clinical department of Neurology

Belgrade, 11000, Serbia

Location

University Clinical Center of Serbia, Clinic for Neurology

Belgrade, 11000, Serbia

Location

University Clinical Center Kragujevac, Clinic for Neurology (Site 601)

Kragujevac, 34000, Serbia

Location

University Clinical Center Kragujevac, Clinic for Neurology (Site 602)

Kragujevac, 34000, Serbia

Location

Related Publications (3)

• 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.

  PMID: 32358047 BACKGROUND

• 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.

  PMID: 32358046 BACKGROUND

• 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.

  PMID: 30534585 BACKGROUND

MeSH Terms

Conditions

Parkinson Disease

Interventions

mesdopetam

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Results Point of Contact

• Title: Joakim Tedroff, Chief Medical Officer
• Organization: Integrative Research Laboratories Sweden AB

joakim.tedroff@irlab.se

+46707601691

Study Officials

• Joakim Tedroff

  Integrative Research Laboratories AB (IRLAB)

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 15, 2020
• First Posted: June 17, 2020
• Study Start: October 29, 2020
• Primary Completion: December 2, 2022
• Study Completion: December 9, 2022
• Last Updated: March 6, 2024
• Results First Posted: March 6, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

SE (4); FR (6); IL (5); IT (5); US (14); PL (10)