E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Early Idiopathic Parkinson’s disease |
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E.1.1.1 | Medical condition in easily understood language |
Parkinson’s disease in its early stage |
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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 evaluate the efficacy of once-daily 50 mg opicapone as add-on to stable L DOPA/DDCI therapy in patients with early-stage Parkinson’s disease. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the safety and tolerability of once-daily 50 mg opicapone as add-on to stable L DOPA/DDCI therapy in patients with early-stage Parkinson’s disease. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Subjects must be 30 to 80 years of age, inclusive, at the time of signing the ICF.
2.Diagnosed with idiopathic PD according to the UK PD Society Brain Bank or MDS clinical diagnostic criteria within the previous 5 years.
3.Disease severity Stages 1 to 2.5 (according to the modified Hoehn & Yahr staging)
4.An MDS-UPDRS Part III score of ≥20
5.Receiving treatment with L-DOPA/DDCI for at least 1 year, and at a stable regimen for at least 4 weeks prior to Visit 2
6.Naive to COMT inhibitors (including OPC).
(refer to protocol for exhaustive list of inclusion criteria) |
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E.4 | Principal exclusion criteria |
1.Non-idiopathic PD (for example, atypical parkinsonism, secondary [acquired or symptomatic] parkinsonism, Parkinson-plus syndrome).
2.Signs of motor complications with a total score of MDS-UPDRS Part IV A+B+C greater than ‘0’ (zero)
3.Treatment with prohibited medication: COMT inhibitors (eg, entacapone, tolcapone), antiemetics with antidopaminergic action (except domperidone) or Duopa™ (carbidopa/levodopa intestinal gel) within the 4 weeks before screening.
4.Concomitant use of monoamine oxidase (MAO-A and MAO-B) inhibitors (e.g. phenelzine, tranylcypromine and moclobemide) other than those for the treatment of PD.
5.Previous or planned (during the entire study duration) deep brain stimulation.
6.Previous stereotactic surgery (eg, pallidotomy, thalamotomy) for PD or with planned stereotactic surgery during the study period.
7.Any investigational medicinal product within the 3 months (or within 5 half-lives, whichever is longer) before screening.
8.Any medical condition that might place the subject at increased risk or interfere with study assessments.
9.Past (within the past year) or present history of suicidal ideation or suicide attempts, as determined by a positive response (‘Yes’) to either Question 4 or Question 5 on the suicidal ideation portion of the Columbia-Suicide Severity Rating Scale (C-SSRS) (Screening questions)
(refer to protocol for exhaustive list of exclusion criteria) |
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E.5 End points |
E.5.1 | Primary end point(s) |
Double Blind: Change from baseline (Visit 2) to the end of the double-blind period (Visit 9) in Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part III total score.
Open Label: Change from open-label baseline (Visit 9) to the end of the open-label period (Visit 15) in MDS-UPDRS Part IV total score. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Visit 2, Visit 9, Visit 15
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E.5.2 | Secondary end point(s) |
Double Blind:
1. Change from baseline (Visit 2) to post-baseline visits during the double blind period in the scores of: MDS-UPDRS, Modified Hoehn & Yahr staging, Schwab and England scale, Parkinson’s Disease Sleep Scale 2 (PDSS-2), Non-Motor Symptoms Scale (NMSS), Parkinson’s Disease Questionnaire (PDQ-39) and 9-item Wearing-off questionnaire (WOQ 9).
2. Proportion of subjects with an improvement relative to their condition before the beginning of treatment in Clinical Global Impression of Improvement (CGI-I ) total score at post double-blind baseline visits during the double-blind period.
3. Proportion of subjects with an improvement relative to their condition at admission to the study in Patient’s Global Impression of Improvement (PGI-I) total score at post double blind baseline visits during the double-blind period
Open Label:
1. Change from double-blind baseline (Visit 2) and open-label baseline (Visit 9) to post-baseline visits in the scores of: MDS-UPDRS, Modified Hoehn & Yahr staging, Schwab and England scale, PDSS-2, NMSS, PDQ-39 and WOQ-9.
2. Proportion of subjects with an improvement relative to their condition before the beginning of treatment in CGI-I total scores at open-label visits during the open-label period.
3.Proportion of subjects with an improvement relative to their condition at admission to the study in PGI-I total score at open-label visits during the open-label period
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Visit 2, Visit 9, Visit 15 |
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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 | Yes |
E.6.4 | Safety | Yes |
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 | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Double Blind, randomized and parallel group with an Open-Label Extension |
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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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 63 |
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 |
Serbia |
Turkey |
Ukraine |
Belgium |
Bulgaria |
France |
Germany |
Italy |
Poland |
Portugal |
Spain |
United Kingdom |
Czechia |
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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
|
The end of the study is defined as the date of the last visit assessment of the last subject in the open-label period of the study. |
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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 | 8 |
E.8.9.1 | In the Member State concerned days | 15 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 15 |