Early ParkinSon wIth L-DOPA/DDCI and OpicapoNe (EPSILON Study)

NCT04978597 | Completed Phase 3

• 2 other identifiers: BIA-91067-3032020-005011-52
• Study Type: interventional
• Target: 410
• Locations: 1 country
• Sites: 1

Brief Summary

Opicapone (OPC) is a third generation catechol O methyltransferase (COMT) inhibitor (COMTi) developed by BIAL-Portela \& Cª, S.A. It is approved as adjunctive therapy to preparations of L-DOPA/DDCI in adult patients with Parkinson's disease and end-of-dose motor fluctuations who cannot be stabilized on those combinations. Carbidopa and benserazide are both DDCIs used in association with L DOPA. When OPC is co administered with L DOPA/DDCI, peripheral COMT is inhibited and thus L DOPA plasma levels increase, increasing L DOPA bioavailability. The purpose of this Phase III study is to explore the potential of OPC to enhance the clinical benefit of L-DOPA in L DOPA treated patients in the early stages of Parkinson's Disease (PD) (patients without end-of-dose motor fluctuations, 'non fluctuators').

Conditions

Parkinson

Outcome Measures

Primary Outcomes (2)

• 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

  Double-Blind Period. Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III questionnaire will be collected at visits 2, 3, 4, 6 and 9. MDS-UPDRS is a multimodal scale assessing impairment and disability consisting of 4 parts. Part III assesses the motor signs of PD and is rated by the investigator (score range 0-132). Part III contains 33 scores based on 18 items. A higher score indicates more severe symptoms of PD.

  Up to 24 weeks

• Change from open-label baseline (Visit 9) to the end of the open-label period (Visit 15) in MDS-UPDRS Part IV total score.

  Open-Label Period. Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part IV questionnaire will be collected at Visits 9, 10, 11, 12, 13, 14 and 15. MDS-UPDRS is a multimodal scale assessing impairment and disability consisting of 4 parts. Part IV assesses the motor complications of PD, comprises 6 item (3 items for dyskinesia and 3 items for fluctuation; score range 0-24) and requires the physician to use historical and objective information to assess dyskinesia and motor fluctuations. A higher score indicates more severe symptoms of PD.

  Up to 1-year.

Study Arms (2)

Opicapone

EXPERIMENTAL

OPC will be taken orally once daily in the evening at least 1 hour after the last daily dose of L-DOPA/DDCI (considered the bedtime dose).

Drug: Opicapone 50 mg

Matching placebo

PLACEBO COMPARATOR

Matching placebo will be taken orally once daily in the evening at least 1 hour after the last daily dose of L-DOPA/DDCI (considered the bedtime dose).

Drug: Placebo

Interventions

Opicapone 50 mg DRUG

Capsule, 50 mg, Oral. Swallow whole with water, once daily at bedtime at least 1 hour after L-DOPA/DDCI

Opicapone

Placebo DRUG

Capsule of to matching placebo, Oral. Swallow whole with water, once daily at bedtime at least 1 hour after L-DOPA/DDCI

Matching placebo

Eligibility Criteria

• Age: 30 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Capable of giving signed informed consent.
• Subjects must be 30 to 80 years of age, inclusive, at the time of signing the ICF.
• 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 to 2.5 (according to the modified Hoehn \& Yahr staging)
• Signs of treatable motor disability for a minimum of 4 weeks before screening, with minimum threshold with MDS-UPDRS Part III score of ≥20 at both screening and Visit 2, despite stable anti-PD therapy (based on the investigator's judgment).
• Receiving treatment with L-DOPA/DDCI (either controlled-release, immediate-release or combined controlled immediate-release) for at least 1 year, and at a stable regimen for at least 4 weeks prior to Visit 2 at a daily dose in the range 300 to 500 mg, 3 to 4 times a day.
• Naive to COMT inhibitors (including OPC).
• Male or female.
• A male subject must agree to use contraception during the treatment period and until the PSV, and refrain from donating sperm during this period.
• A female subject is eligible to participate if she is not pregnant , not breastfeeding, and at least 1 of the following conditions applies: i) Not a woman of childbearing potential (WOCBP) OR ii) A WOCBP who agrees to follow the contraceptive guidance during the treatment period and until the PSV.
• Results of the screening laboratory tests are considered clinically acceptable by the Investigator (ie, not clinically relevant for the well-being of the subject or for the purpose of the study).

You may not qualify if:

• Non-idiopathic PD (for example, atypical parkinsonism, secondary \[acquired or symptomatic\] parkinsonism, Parkinson-plus syndrome).
• Signs of motor complications with a total score of MDS-UPDRS Part IV A+B+C greater than '0' (zero).
• 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.
• Concomitant use of monoamine oxidase (MAO-A and MAO-B) inhibitors (eg, phenelzine, tranylcypromine and moclobemide) other than those for the treatment of PD.
• Previous or planned (during the entire study duration) deep brain stimulation.
• Previous stereotactic surgery (eg, pallidotomy, thalamotomy) for PD or with planned stereotactic surgery during the study period.
• Any investigational medicinal product within the 3 months (or within 5 half-lives, whichever is longer) before screening.
• Any medical condition that might place the subject at increased risk or interfere with study assessments.
• 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)
• Current or previous (within the past year) diagnosis of psychosis, severe major depression, or other psychiatric disorders that, based on the Investigator's judgment, might place the subject at increased risk or interfere with assessments.
• A clinically relevant electrocardiogram (ECG) abnormality (relevance should be assessed by a cardiologist if needed).
• Current evidence of unstable cardiovascular disease, including but not limited to uncontrolled hypertension, myocardial infarction with important systolic or diastolic dysfunction, unstable angina, congestive heart failure (New York Heart Association Class ≥III), and significant cardiac arrhythmia (Mobitz II 2nd or 3rd degree AV block or any other arrhythmia causing hemodynamic repercussions as symptomatic bradycardia or syncope).
• Prior renal transplant or current renal dialysis.
• Pheochromocytoma, paraganglioma or other catecholamine secretive neoplasm.
• Known hypersensitivity to any ingredients of the study treatment.

Sponsors & Collaborators

• Bial - Portela C S.A.: lead

Study Sites (1)

Medical Centre "Asklepii", OOD

Dupnitsa, 2600, Bulgaria

Location

Related Links

• EU Clinical Trials Register
• Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS)

MeSH Terms

Interventions

opicapone

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 5, 2021
• First Posted: July 27, 2021
• Study Start: May 31, 2021
• Primary Completion: January 11, 2023
• Study Completion: January 26, 2024
• Last Updated: March 12, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

BU (1)