E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Parkinson's disease patients with wearing-off motor fluctuations and associated pain. |
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E.1.1.1 | Medical condition in easily understood language |
Parkinson’s disease patients with associated movement disorders and pain. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061536 |
E.1.2 | Term | Parkinson's disease |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To investigate the efficacy of 50 mg opicapone when administered with the existing treatment of L-dopa plus a DDCI, in PD patients with end-of-dose motor fluctuations and associated pain |
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E.2.2 | Secondary objectives of the trial |
•To investigate the efficacy of opicapone 50 mg in reducing further symptoms •To investigate the safety and tolerability of opicapone 50 mg once daily |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
At Visit 1 (Screening), patients must meet ALL of the following criteria: 1. Able to comprehend and willing to sign an informed consent form and to comply with all aspects of the study. 2. Male or female patients aged 30 years or older. 3. Experiencing PD associated pain for at least 4 weeks prior to V1. 4. Diagnosed with idiopathic PD according to the UK Parkinson’s Disease Society Brain Bank Clinical Diagnostic Criteria (2006) or according to MDS Clinical Diagnostic Criteria (2015). 5. Disease severity Stages I-III (modified Hoehn & Yahr staging) at ON. 6. Treated with 3 to 8 intakes per day of L-dopa/DDCI (which may include a slow-release formulation), on a stable regimen for at least 4 weeks before V1. 7. In case of any other anti-PD-treatment, it should be on a stable regimen for at least 4 weeks before V1, and not likely to need any adjustment until V6. 8. No changes in chronic treatment regimen for pain within the last 4 weeks before V1. This includes medication (including but not limited to paracetamol, opioids, nonsteroidal anti-inflammatory drugs [NSAIDS], antidepressants, anticonvulsants and corticosteroids) and non-medication therapies (including but not limited to transcutaneous electrical nerve stimulation and bioelectrical therapy). 9. Signs of “wearing-off” phenomenon (end-of-dose motor fluctuations) with average total daily OFF time while awake of at least 1.5 hours, excluding the early morning pre-first dose OFF, despite optimal anti-PD therapy (based on investigator’s assessment). 10. Domain 3 of KPPS ≥ 12. 11. For females: Postmenopausal for at least 2 years before V1, surgically sterile for at least 6 months before V1, or practicing effective contraception until V6. Female patients who request to continue with oral contraceptives must be willing to use non-hormonal methods of contraception in addition during the course of this study. For males: Male patients who are sexually active with a partner of childbearing potential must use, with their partner, a condom plus an approved method of highly effective contraception during the treatment period until V6. At Visit 2b (Baseline), patients must meet ALL of the following criteria: 12. Have filled-in self-rating diary in accordance with the diary instructions and with ≤ 3 missing entries per day, in the 3 days preceding V2a/V2b. 13. With at least 1.5 OFF hours per day, excluding the early morning pre-first dose OFF period (i.e. the time between wake-up and response to the first L-dopa/DDCI dosage), as recorded in at least 2 of the 3 days in the self-rating diary for the 3 days preceding V2a/V2b. 14. Results of the screening laboratory tests are considered acceptable by the investigator (i.e. not clinically relevant for the well-being of the patient or for the purpose of the study). 15. Domain 3 of KPPS ≥ 12. 16. Adequate compliance to relevant (PD and pain related) concomitant medication during the screening period (based on the investigator’s judgment). |
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E.4 | Principal exclusion criteria |
Criterion: 1. Non-idiopathic PD (atypical parkinsonism, secondary [acquired or symptomatic] parkinsonism, Parkinson-plus syndrome). 2. Severe and/or unpredictable OFF periods, according to investigator judgement. 3. Major/prominent non-PD-related pain (e.g. due to malignant disease). 4. Treatment with prohibited medication: entacapone, tolcapone, monoamine oxidase (MAO) inhibitors (except selegiline up to 10 mg/day in oral formulation or 1.25 mg/day in buccal absorption formulation, rasagiline up to 1 mg/day or safinamide up to 100 mg/day), or antiemetics with antidopaminergic action (except domperidone) within the last 4 weeks before V1. 5. Previous or planned (during the entire study duration) L-dopa/carbidopa intestinal gel infusion, brain stimulation or stereotactic surgery (e.g. pallidotomy, thalamotomy). 6. Treatment with apomorphine within the last 4 weeks before V1 or likely to be needed at any time until V6. 7. Previous or current use of opicapone. 8. Use of any other IP, currently or within the 3 months (or within 5 half-lives of the IP, whichever is longer) before V1. 9. Past (within the past year) or present history of suicidal ideation or suicide attempts. 10. Current or previous (within the past year) alcohol or substance abuse excluding caffeine or nicotine. 11. Phaeochromocytoma, paraganglioma, or other catecholamine secreting neoplasms. 12. Known hypersensitivity to the excipients of IP (including lactose intolerance, galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption) or of rescue medication. 13. History of neuroleptic malignant syndrome or non-traumatic rhabdomyolysis. 14. History of severe hepatic impairment (Child-Pugh Class C). 15. Previous history of psychosis or psychiatric disorders, including severe major depression. 16. Any medical condition that might place the patient at increased risk or interfere with assessments. 17. For females: Pregnant or breastfeeding. 18. Employees of the investigator, study centre, sponsor, clinical research organisation and study consultants, when employees are directly involved in this study or other studies under the direction of this investigator or study centre, and their family members. 19. Persons committed to an institution by virtue of an order issued either by the judicial or other authorities. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in Domain 3 (fluctuation-related pain) of King’s Parkinson’s Disease Pain Scale (KPPS) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1.Change from baseline in Domain B (anxiety) of Movement Disorder Society-sponsored Non-motor Rating Scale (MDS-NMS) (Key secondary endpoint) 2.Change from baseline in Domain A (depression) of MDS-NMS 3.Change from baseline in Domain K (sleep and wakefulness) of MDS-NMS 4.Change from baseline in total score of MDS-NMS 5.Change from baseline in Domain 4 (nocturnal pain) of KPPS 6.Change from baseline in total score of KPPS 7.Change from baseline in Movement Disorder Society-sponsored Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part III and IV 8.Change from baseline in Parkinson’s Disease Questionnaire (PDQ-8) 9.Clinical Global Impression of Change (CGIC) 10.Patient’s Global Impression of Change (PGIC) 11.Change from baseline in functional status via Hauser’s PD diary 12.Changes from baseline in morning dystonia 13.Frequency of use of rescue medication 14.Incidence of adverse events (AEs) including serious adverse events (SAEs) 15.Changes from baseline in vital signs 16.Changes from baseline in physical and neurological examinations 17.Changes from baseline in routine laboratory parameters |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 60 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
United Kingdom |
Czechia |
Germany |
Italy |
Poland |
Portugal |
Spain |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 0 |