Efficacy and Tolerability of IRL790 in Parkinson's Disease Dyskinesia
Condition: Parkinson Disease
MeSH terms: Parkinson Disease; Dyskinesias
Intervention: Mesdopetam (IRL790)
Intervention description: Mesdopetam (IRL790) capsule
Intervention MeSH terms: Mesdopetam
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Double blind, placebo controlled
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 75.0
Sex: All
Minimum age: 18 Years
Maximum age: 79 Years
Healthy volunteers: No
Keywords: Levodopa induced dyskinesia

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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male or female ≥18 and ≤79 years of age.

          2. Signed a current Ethics Committee approved informed consent form.

          3. Parkinson's disease, per UK Parkinson's Disease Society (UKPDS) Brain Bank Clinical
             Diagnostic Criteria.

          4. Waking day dyskinesia of ≥25% determined as a score of ≥2 as per Question 4.1 of the
             MDS-UPDRS.

          5. 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.

          6. Taking a maximum of eight regular levodopa intakes per day, excluding bedtime and
             night time levodopa.

          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 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).

          8. Patient must be willing and able to avoid direct exposure to sunlight from day 1 to
             day 28.

          9. Able to complete at least one valid 24-hour patient diary at Visit 1.

        Exclusion Criteria:

          1. History of neurosurgical intervention related to Parkinson's disease (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, localised bladder cancer,
             non-metastatic prostate cancer or in situ cervical cancer.

          6. Presence of cognitive impairment, as evidenced by a Mini-Mental Status Examination
             (MMSE) score of less than 24 during screening.

          7. A Hoehn and Yahr score of five when "off" as per Question 3.18 of the MDS-UPDRS,
             assessed during screening.

          8. 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

          9. 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.

         10. 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.

         11. 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.

         12. Drug and/or alcohol abuse.

         13. History of severe drug allergy or hypersensitivity.

         14. If female, is pregnant or lactating, or has a positive pregnancy test result pre-dose.

         15. Patients unwilling to use two forms of contraception 90 days for men and 30 days for
             women after last IMP dose

         16. Any planned major surgery within the duration of the study.

         17. Any other condition or symptoms preventing the patient from entering the study,
             according to the Investigator's judgement.