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This is a Phase 1b study investigating the safety and tolerability of IRl790 as adjunct therapy in patients with Parkinson disease. IRL790/placebo is taken for 28 days.
Consenting patients were screened for eligibility as per study-specific inclusion/exclusion criteria within 8-28 days before start of Investigational Medicinal Product (IMP) administration (Visit 1; Screening Visit). At Visit 2 (Day -7) a kinetigraph device (the Parkinson's KinetiGraphâ„¢, Global Kinetics Corporation, Melbourne, Victoria, Australia) was attached to the right or left wrist (the parkinsonian dominant side) and baseline patient movement data were recorded during a run-in period of seven consecutive days.
Following baseline assessments at Visit 3 (Day 1) patients were randomized to receive IRL790 or placebo (3:1). The treatment allocation was double-blinded, i.e. it was not disclosed to the patients, the site staff or the Sponsor. During the treatment period, Visits 4-8 were performed on Days 4, 7, 10, 14 and 28 (end of treatment) and a follow-up phone call was performed on Day 21. Dose adjustments of IRL790 could be made until Day 14, following pre-defined criteria. A follow-up visit (Visit 9) was performed 7-10 days after the last IMP dose.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| IRL790 | Experimental | IRL790 Capsule 10 mg, oral administration |
|
| Placebo | Placebo Comparator | Placebo capsule, identical appearance, oral administration |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| IRL790 | Drug | IRL790 capsule 10 mg |
| |
| Placebo |
| Measure | Description | Time Frame |
|---|---|---|
| Adverse Events | Medical Dictionary for Regulatory Activities Preferred Term | 4 weeks |
| Physical examination | Number of participants with clinically significant abnormal physical examination findings | 4 weeks |
| Electrocardiogram (ECG) recordings | Number of participants with clinically significant abnormal electrocardiogram readings | 4 weeks |
| Heart rate | Beats per minute | 4 weeks |
| Blood pressure | mm Hg | 4 weeks |
| Safety laboratory measurements | Number of participants with clinically significant abnormal laboratory values | 4 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| 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 UDysRS is administered to assess dyskinesia. The scoring range is 0-104, where higher score means more dyskinesia. | 4 weeks |
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Inclusion Criteria:
Exclusion Criteria:
9. Prolonged QTcF (>450 ms), cardiac arrhythmias or any clinically significant abnormalities in the resting ECG at the time of screening, as judged by the Investigator.
10. History of severe allergy/hypersensitivity or on-going allergy/hypersensitivity, as judged by the Investigator, or history of hypersensitivity to drugs with a similar chemical structure or class to IRL790. 11. Administration of another new chemical entity (defined as a compound which has not been approved for marketing) or participation in any other clinical study that included drug treatment with less than three months between administration of last dose and first dose of IMP in this study. 12. History of alcohol abuse and/or use of drugs of abuse. 13. Investigator considered the patient unlikely to comply with study procedures, restrictions and requirements.
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| Name | Affiliation | Role |
|---|---|---|
| Per Svenningsson, MD, PhD | Karolinska Institutet, Stockholm | Principal Investigator |
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| ID | Term |
|---|---|
| D010300 | Parkinson Disease |
| ID | Term |
|---|---|
| D020734 | Parkinsonian Disorders |
| D001480 | Basal Ganglia Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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| ID | Term |
|---|---|
| C000722506 | mesdopetam |
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| Drug |
Placebo capsule |
|
| Unified Parkinson's Disease Rating Scale (UPDRS) |
The UPDRS assess symptoms of Parkinson's disease. The scoring range from 0-199, where higher score means more severe disease. |
| 4 weeks |
| Parkinson Kinetigraph (PKG) | Wrist worn kinetigraph capturing electronic readings of movement activity. | Change from run-in to week 4 of treatment |
| Clinical Global impression of change (CGI-C) | Global impression of change | 4 weeks |
| Pharmacokinetic assessment | Plasma concentration at Cmax | 4 weeks |
| Pharmacokinetic assessment | Trough level plasma concentration | 4 weeks |
| D009422 | Nervous System Diseases |
| D009069 | Movement Disorders |
| D000080874 | Synucleinopathies |
| D019636 | Neurodegenerative Diseases |