Efficacy and Tolerability of IRL790 in Parkinson's Disease Dyskinesia

NCT03368170 | Completed Phase 2 Results DMC

• 1 other identifier: IRL790C003
• Study Type: interventional
• Target: 75
• Locations: 2 countries
• Sites: 20

Brief Summary

Mesdopetam (IRL790) is an experimental small molecule compound with psychomotor stabilizing properties. The primary target is the dopamine D3 receptor, a target implicated in the generation of levodopa-induced dyskinesia, a side-effect frequently occurring with long-term levodopa treatment in patients with Parkinson's disease. In experimental animals mesdopetam potently reduced levodopa-induced involuntary movement without impairing the antiparkinsonian effect of levodopa. The primary purpose of the trial is to investigate whether mesdopetam given as adjunctive treatment can reduce levodopa induced dyskinesia in patients with Parkinson's disease. The trial will also help to establish the most optimal dosing of the compound.

Conditions

Parkinson Disease

Keywords

Levodopa induced dyskinesia

Outcome Measures

Primary Outcomes (1)

• Unified Dyskinesia Rating Scale (UDysRS)

  The change from baseline to day 28 of treatment (Visit 4) in the sum of the items comprising the Unified Dyskinesia Rating Scale (UDysRS). The Unified Dyskinesia Rating Scale (UDysRS) is administered to assess dyskinesia. The scoring range is 0-104, where higher score means more dyskinesia.

  Baseline and 4 weeks

Secondary Outcomes (2)

• Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part IV, Question 4.1 and 4.2

  Baseline and 4 weeks

• Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Part II and III

  Baseline and 4 weeks

Other Outcomes (1)

• Change in Daily Hours Spent in ON-time With Troublesome Dyskinesia as Assessed by 24-hour Patient Diaries

  Run-in and 4 weeks

Study Arms (2)

Mesdopetam (IRL790)

EXPERIMENTAL

Capsule 2.5 mg, oral administration

Drug: Mesdopetam (IRL790)

Placebo

PLACEBO COMPARATOR

Identical capsule, oral administration

Drug: Mesdopetam (IRL790)

Interventions

Mesdopetam (IRL790) DRUG

Mesdopetam (IRL790) capsule

Also known as: IRL790

Mesdopetam (IRL790); Placebo

Eligibility Criteria

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

You may qualify if:

• Male or female ≥18 and ≤79 years of age.
• Signed a current Ethics Committee approved informed consent form.
• Parkinson's disease, per UK Parkinson's Disease Society (UKPDS) Brain Bank Clinical Diagnostic Criteria.
• Waking day dyskinesia of ≥25% determined as a score of ≥2 as per Question 4.1 of the MDS-UPDRS.
• On a stable regimen of antiparkinson medications for at least 30 days prior to screening, including a levodopa preparation administered not less than three times daily and willing to continue the same doses and regimens during study participation. Rescue medication such as Madopar dispersable and Apomorphine injections are allowed.
• Taking a maximum of eight regular levodopa intakes per day, excluding bedtime and night time levodopa.
• 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 screening 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).
• Patient must be willing and able to avoid direct exposure to sunlight from day 1 to day 28.
• Able to complete at least one valid 24-hour patient diary at Visit 1.

You may not qualify if:

• History of neurosurgical intervention related to Parkinson's disease (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, localised bladder cancer, non-metastatic prostate cancer or in situ cervical cancer.
• Presence of cognitive impairment, as evidenced by a Mini-Mental Status Examination (MMSE) score of less than 24 during screening.
• A Hoehn and Yahr score of five when "off" as per Question 3.18 of the MDS-UPDRS, assessed during screening.
• 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; clinically significant hepatic disease, renal failure or abnormal renal function.
• Any history of a neurological other than Parkinson's disease or a psychiatric disorder, including history of 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.
• If female, is pregnant or lactating, or has a positive pregnancy test result pre-dose.
• Patients unwilling to use two forms of contraception 90 days for men and 30 days for women after last IMP dose

Sponsors & Collaborators

• Integrative Research Laboratories AB: lead
• The Clinical Trial Company: collaborator

Study Sites (20)

Sahlgrenska University hospital

Gothenburg, Sweden

Location

University hospital

Linköping, Sweden

Location

University hospital

Lund, Sweden

Location

Karolinska University hospital

Stockholm, Sweden

Location

Bristol Brain Centre, Southmead Hospital

Bristol, United Kingdom

Location

Fairfield General Hospital (Pennine Acute NHS Trust)

Bury, United Kingdom

Location

Ninewells Hospital

Dundee, United Kingdom

Location

Lincoln County Hospital

Lincoln, United Kingdom

Location

Charing Cross Hospital, Imperial College Healthcare NHS Trust

London, United Kingdom

Location

The National Hospital of Neurology and Neurosurgery (UCL)

London, United Kingdom

Location

Luton and Dunstable University Hospital NHS Foundation Trust

Luton, United Kingdom

Location

North Tyneside General Hospital

North Shields, United Kingdom

Location

Qeens' Medical Centre

Nottingham, United Kingdom

Location

John Radcliffe Hospital

Oxford, United Kingdom

Location

Peterborough City Hospital

Peterborough, United Kingdom

Location

Plymouth Hospitals NHS Trust - Derriford Hospital

Plymouth, PL6 8DH, United Kingdom

Location

Queens's Hospital

Romford, United Kingdom

Location

Royal Stoke University Hospital

Stoke-on-Trent, United Kingdom

Location

Torbay hospital

Torquay, United Kingdom

Location

Royal Cornwall Hospital

Truro, United Kingdom

Location

Related Publications (1)

• McFarthing K, Prakash N, Simuni T. CLINICAL TRIAL HIGHLIGHTS - DYSKINESIA. J Parkinsons Dis. 2019;9(3):449-465. doi: 10.3233/JPD-199002. No abstract available.

  PMID: 31356217 DERIVED

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

Limitations and Caveats

There were technical difficulties in the administration of UDysRS objective score. It was not administered in a manner that would enable an unambiguous interpretation of the results.

Results Point of Contact

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

joakim.tedroff@irlab.se

+ 46 707 601691

Study Officials

• Camille Carroll, MD

  Plymouth University Peninsula Schools of Medicine and Dentistry

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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

Model Details: Double blind, placebo controlled

Study Record Dates

• First Submitted: December 5, 2017
• First Posted: December 11, 2017
• Study Start: April 12, 2018
• Primary Completion: June 12, 2019
• Study Completion: June 12, 2019
• Last Updated: March 31, 2022
• Results First Posted: March 24, 2020

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

SE (4); GB (16)