Why carry out this study?
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Levodopa remains the cornerstone treatment for Parkinson’s disease (PD) but its use is associated with the development of wearing-off fluctuations and other motor and non-motor complications. |
The addition of a catechol-O-methyltransferase (COMT) inhibitor to levodopa therapy increases plasma levodopa levels and reduces fluctuations following oral dosing. |
Opicapone (OPC; a third-generation, once-daily COMT inhibitor) ensures a substantial and prolonged inhibition of COMT over 24 h and increases the overall systemic exposure to levodopa. |
EPSILON is a phase III, randomised, double-blind, placebo-controlled trial and open-label extension study that will evaluate the efficacy of OPC in enhancing the clinical benefit of levodopa in patients in the early stages of PD, without end-of-dose motor fluctuations. |
What will be learned from the study?
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EPSILON will evaluate the impact of adding OPC to levodopa therapy on motor symptoms in patients with early PD who do not exhibit signs of motor complications. |
Introduction
Methods
Study Design
Treatment Allocation
Treatment Groups and Duration
Dose Regimen
Study Population
Category of characteristic | Inclusion criteria | Exclusion criteria |
---|---|---|
Demographics | Male or female Aged 30–80 years | |
Disease-related characteristics | Diagnosed with idiopathic PD according to the UK Parkinson’s Disease Society Brain Bank Clinical Diagnostic Criteria within the previous 5 years Disease severity stages 1–2.5a Signs of treatable motor disability for ≥ 4 weeks before screening, with minimum threshold with MDS-UPDRS Part III score of ≥ 20 at both screening and V2, despite stable anti-PD therapyb | Non-idiopathic PD Signs of motor complications with a total score of MDS-UPDRS Part IV A + B + C greater than ‘0’ (zero) |
Anti-PD medication | Receiving treatment with l-DOPA/DDCI (either controlled-release, immediate-release or combined controlled/immediate-release) for ≥ 1 year, and at a stable regimen for ≥ 4 weeks prior to V2 at a daily dose of 300–500 mg, 3 to 4 times a day | Treatment with prohibited medicationc within the 4 weeks prior to screening Previous or current use of COMTI (including OPC) Previous or planned (during the entire study duration) deep brain stimulation Previous stereotactic surgery (e.g. pallidotomy, thalamotomy) for PD or with planned stereotactic surgery during the study period Use of any other investigational product, currently or within 3 months (or 5 half-lives of the investigational product, whichever is longer) prior to screening |
Compliance | Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the study protocol | |
Safety | For female patients: not of childbearing potential, or of childbearing potential but agrees to follow contraceptive during the treatment period and until the PSVd For male patients: use of contraception during the treatment period and until the PSV, and refrain from donating sperm during this period | Current or past (within previous year) history of suicidal ideation or suicide attempts Clinically relevant electrocardiogram abnormality Current evidence of unstable cardiovascular diseasee Prior renal transplant or current renal dialysis Pheochromocytoma, paraganglioma or other catecholamine-secreting neoplasms Known hypersensitivity to the excipients of the investigation productf or rescue medication History of neuroleptic malignant syndrome or non-traumatic rhabdomyolysis Current or past (within previous year) history of psychosis or psychiatric disorders, including severe major depression Malignancy within the past 5 yearsg Unstable active narrow-angle or unstable wide-angle glaucoma Any medical condition that might place the patient at increased risk or interfere with assessments For female patients: pregnant or breastfeeding |
Laboratory parameters | Acceptable results of screening laboratory tests (i.e. not clinically relevant for the well-being of the patient or for the purpose of the study according to investigator’s judgment) | Any abnormality in ALT or AST > 2 times the ULN range, in the screening laboratory tests results Plasma sodium < 130 mmol/L, white blood cell count < 3000 cells/mm3, or any other relevant clinical laboratory abnormality that, in the investigator’s opinion, may compromise the patient’s safety |
Study Assessments
Double-blind period | |
Primary endpoint | Change from baseline (V2) to the end of the double-blind period (V9) in MDS-UPDRS Part III total score |
Secondary endpoints | Change from baseline (V2) to post-baseline visits during the double-blind period in: MDS-UPDRS total scores: Parts I, II, III and IV, and Part II + III Modified Hoehn & Yahr staging total score Schwab and England ADL scale score PDSS-2 total score NMSS total and subdomain scores PDQ-39 total and subdomain scores WOQ-9: Presence of wearing-off, total and subsection (motor and non-motor) scores Proportion of patients with an improvement from baseline (V2) in CGI-I total score at post-baseline visits during the double-blind period Proportion of patients with an improvement from baseline (V2) in PGI-I total score at post-baseline visits during the double-blind period |
Open-label period | |
Primary endpoint | Change from open-label baseline (V9) to the end of the open-label period (V15) in MDS-UPDRS Part IV total score |
Secondary endpoints | Change from double-blind baseline (V2) and open-label baseline (V9) to post-baseline visits in: MDS-UPDRS total scores: Parts I, II, III and IV, and Part II + III Modified Hoehn & Yahr staging total score Schwab and England ADL scale score PDSS-2 total score NMSS total and subdomain scores PDQ-39 total and subdomain scores WOQ-9: Presence of wearing-off, total and subsection (motor and non-motor) scores Proportion of patients with an improvement from open-label baseline (V9) in CGI-I total score at post-baseline visits during the open-label period Proportion of patients with an improvement from open-label baseline (V9) in PGI-I total score at post-baseline visits during the open-label period |
Safety endpoints (both double-blind and open-label periods) | TEAEs including SAEs Laboratory safety tests (biochemistry, haematology, and urinalysis) Physical and neurological examinations Vital signs 12-lead ECG readings C-SSRS mMIDI |