A Clinical Study of Mesdopetam in Patients With Parkinson's Disease Experiencing Levodopa Induced Dyskinesia
|
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT04435431 |
|
Recruitment Status :
Completed
First Posted : June 17, 2020
Last Update Posted : December 15, 2022
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Parkinson Disease | Drug: Mesdopetam Drug: Placebo | Phase 2 |
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 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 MDS-UPDRS, the modified 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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 156 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | A Randomized, Double-blind, Placebo-controlled Phase IIB Study Evaluating the Efficacy of Mesdopetam on Daily ON-time Without Troublesome Dyskinesia in Patients With Parkinson's Disease |
| Actual Study Start Date : | October 29, 2020 |
| Actual Primary Completion Date : | December 2, 2022 |
| Actual Study Completion Date : | December 9, 2022 |
| Arm | Intervention/treatment |
|---|---|
|
Experimental: Mesdopetam dose 1
Mesdopetam capsule (mg), dose 1, 1 capsule b.i.d. for 84 days.
|
Drug: Mesdopetam
Oral use
Other Name: IRL790 |
|
Experimental: Mesdopetam dose 2
Mesdopetam capsule (mg), dose 2, 1 capsule b.i.d. for 84 days.
|
Drug: Mesdopetam
Oral use
Other Name: IRL790 |
|
Experimental: Mesdopetam dose 3
Mesdopetam capsule (mg), dose 3, 1 capsule b.i.d. for 84 days.
|
Drug: Mesdopetam
Oral use
Other Name: IRL790 |
|
Placebo Comparator: Placebo
Placebo capsule, 1 capsule b.i.d. for 84 days
|
Drug: Placebo
Oral use |
- 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. [ Time Frame: Baseline to end of treatment (week 12) ]This is a self administered diary where patients assess their motor state every half hour during 24 hours. The different motor states assessed: ON, ON with troublesome dyskinesia, OFF and asleep.
- Change from baseline in mean score of ON-phase dyskinesia assessed with the sum score of the modified UDysRS (parts 1, 3 and 4) (with mesdopetam compared to placebo). [ Time Frame: Baseline to end of treatment (week 12) ]The scoring range is 0-88, where higher score means more dyskinesia.
- 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 UDysRS (with mesdopetam compared to placebo). [ Time Frame: Baseline to end of treatment (week 12) ]The scoring range is 0-60, where higher score means more dyskinesia.
- Change from baseline in mean score of ON-phase dyskinesia assessed by MDS-UPDRS part 4 questions 4.1 (Time spent with dyskinesias) and 4.2 (Functional impact of dyskinesias) (with mesdopetam compared to placebo). [ Time Frame: Baseline to end of treatment (week 12) ]Minimum score is 0 and maximum score is 8. A higher score means more dyskinesia.
- 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) [ Time Frame: Baseline to end of treatment (week 12) ]Minimum score is 0 and maximum score is 52. A higher score means more motor symptoms.
- Change from baseline in average daily hours of OFF-time, daily ON-time with troublesome dyskinesia and daily total ON-time (defined as the sum of ON-time with and without troublesome dyskinesia) (with mesdopetam compared to placebo). [ Time Frame: Baseline to end of treatment (week 12) ]This is a self administered diary where patients assess their motor state every half hour during 24 hours. The different motor states assessed: ON, ON with troublesome dyskinesia, OFF and asleep.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 30 Years to 79 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
- If female, is pregnant or lactating, or has a positive pregnancy test result pre-dose.
- 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.
- Any planned major surgery within the duration of the study.
- Any other condition or symptoms preventing the patient from entering the study, according to the Investigator's judgement.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04435431
Show 44 study locations
| Study Director: | Joakim Tedroff | Integrative Research Laboratories AB (IRLAB) |
| Responsible Party: | Integrative Research Laboratories AB |
| ClinicalTrials.gov Identifier: | NCT04435431 |
| Other Study ID Numbers: |
IRL790C005 |
| First Posted: | June 17, 2020 Key Record Dates |
| Last Update Posted: | December 15, 2022 |
| Last Verified: | December 2022 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
|
Parkinson Disease Dyskinesias Parkinsonian Disorders Basal Ganglia Diseases Brain Diseases Central Nervous System Diseases Nervous System Diseases Movement Disorders Synucleinopathies |
Neurodegenerative Diseases Neurologic Manifestations Mesdopetam Dopamine Antagonists Dopamine Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Physiological Effects of Drugs |