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

NCT ID: NCT04435431

Last Updated: 2024-03-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 155 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-10-29
• Study Completion Date: 2022-12-09

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.

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.

Conditions

Parkinson Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Mesdopetam dose 1

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

Group Type: EXPERIMENTAL

Mesdopetam

Intervention Type: DRUG

Oral use

Mesdopetam dose 2

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

Group Type: EXPERIMENTAL

Mesdopetam

Intervention Type: DRUG

Oral use

Mesdopetam dose 3

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

Group Type: EXPERIMENTAL

Mesdopetam

Intervention Type: DRUG

Oral use

Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Oral use

Interventions

Mesdopetam

Oral use

Intervention Type: DRUG

Placebo

Oral use

Intervention Type: DRUG

Other Intervention Names

IRL790

Eligibility Criteria

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.

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 79 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Integrative Research Laboratories AB

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Joakim Tedroff

Role: STUDY_DIRECTOR

Integrative Research Laboratories AB (IRLAB)

Locations

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

University of Kentucky, Department of Neurology

Lexington, Kentucky, United States

The Movement Disorder Clinic of Oklahoma

Tulsa, Oklahoma, United States

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Inland Northwest Research

Spokane, Washington, United States

Centre Hospitalier Regional Universitaire de Lille

Lille, , France

CHU Dupuytren 1 - Neurologie

Limoges, , France

CHU Carémeau

Nîmes, , France

CHU de Poitiers

Poitiers, , France

CHU Rennes-Pontchaillou

Rennes, , France

CHU Charles Nicolle; Service de Neurologie

Rouen, , France

Rambam Health Care Campus, Department of Neurology

Haifa, , Israel

Hadassah University Hospital-Ein Kerem, Department of Neurology

Jerusalem, , Israel

Rabin Medical Centre - Beilinson Hospital, Department of Neurology

Petah Tikva, , Israel

The Chaim Sheba Medical Centre, Department of Neurology

Ramat Gan, , Israel

Tel Aviv Sourasky Medical Centre; Movement Disorders Unit

Tel Aviv, , Israel

IRCCS - Ospedale "San Martino"

Genova, , Italy

Azienda Ospedaliera di Padova

Padua, , Italy

IRCCS San Raffaele Pisana

Roma, , Italy

Fondazione Policlinico Gemelli IRCCS

Roma, , Italy

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

Salerno, , Italy

Centrum Medyczne Neuromed

Bydgoszcz, , Poland

Specjalistyczna Praktyka Lekarska

Katowice, , Poland

Centrum Medyczne PLEJADY

Krakow, , Poland

Specjalistyczne Gabinety Sp z o.o.

Krakow, , Poland

Krakowska Akademia Neurologii

Krakow, , Poland

Instytut Zdrowia

Oświęcim, , Poland

Neuro-Care

Siemianowice Śląskie, , Poland

Centrum Medyczne NeuroProtect

Warsaw, , Poland

Next Stage sp.z o.o.

Warsaw, , Poland

ClinHouse Centrum Medyczne

Zabrze, , Poland

Clinical Hospital Center Zvezdara, Clinical department of Neurology

Belgrade, , Serbia

University Clinical Center of Serbia, Clinic for Neurology

Belgrade, , Serbia

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

Kragujevac, , Serbia

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

Kragujevac, , Serbia

Countries

United States; France; Israel; Italy; Poland; Serbia

References

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.

Reference Type: BACKGROUND

PMID: 32358047 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 32358046 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 30534585 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

IRL790C005

Identifier Type: -

Identifier Source: org_study_id