ParkinsonPhase 3EPSILONNCT04978597
Early ParkinSon wIth L-DOPA/DDCI and OpicapoNe (EPSILON Study)
A Phase 3 study testing Opicapone 50 mg in people with Parkinson, run by Bial - Portela C S.A. at 1 site in Bulgaria.
Trial 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… Read more about this study
- Who is it for?
- Ages 30 to 80 years
- Conditions the study is for
- Parkinson
- What is being tested?
- Opicapone 50 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 410 participants
- Where
- 1 siteBulgaria
- Study dates
- 31 May 2021to 26 Jan 2024
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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).
Who cannot join
- 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.
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- 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.
- History of neuroleptic malignant syndrome (NMS) or NMS-like syndromes, or non-traumatic rhabdomyolysis.
- Malignancy within the past 5 years (eg, melanoma, prostate cancer), excluding cutaneous basal or squamous cell cancer resolved by excision.
- Unstable active narrow-angle or unstable wide-angle glaucoma.
- History of or current evidence of any relevant disease in the context of this study, ie, with respect to the safety of the subject or related to the study conditions, eg, which may influence the absorption or metabolism (such as a relevant liver disease) of the study treatment.
- Any abnormality in the liver enzymes (alanine aminotransferase [ALT] and/or aspartate aminotransferase [AST]) >2 times the upper limit of the normal range, in the screening laboratory tests results.
- Plasma sodium less than 130 mmol/L, white blood cell count less than 3000 cells/mm3, or any other relevant clinical laboratory abnormality that, in the Investigator's opinion, may compromise the subject's safety.
- Positive SARS-CoV-2 test at screening.
- Evidence of an ICD (one or more positive modules on the mMIDI)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase III, Double-Blind, Randomized, Placebo-Controlled and Parallel-Group Study to Evaluate the Efficacy and Safety of Opicapone, as Add-on to Stable Levodopa (L-DOPA) Plus a Dopa Decarboxylase Inhibitor (DDCI) Therapy in Early Idiopathic Parkinson's Disease Patients, With an Open-Label Extension
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').
Read the detailed description
This is a Phase III study to evaluate the efficacy and safety of OPC in subjects with early idiopathic PD receiving treatment with L DOPA plus a DDCI, and who are without signs of any motor complication (consisting of fluctuations in the motor response and/or involuntary movements or dyskinesias).
After a screening period of up to 4 weeks, eligible subjects will be randomized into 1 of 2 treatment arms (OPC 50 mg, or placebo) in a 1:1 ratio, and enter a 24-week placebo-controlled, parallel-group, double blind period.
At the end of the double-blind period, subjects may enter an additional 1-year, open-label period, at the discretion of both the Investigator and subject, in which all subjects will be treated with OPC 50 mg.
A Post-study Visit (PSV) will be performed approximately 2 weeks after the End of Study Visit (EOS) or Early Discontinuation Visit (EDV).
Study treatment will be administered in combination with existing treatment of L-DOPA/DDCI.
- Conditions
- Parkinson
- Being tested
- Opicapone 50 mg, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Opicapone 50 mgDrug
Capsule, 50 mg, Oral. Swallow whole with water, once daily at bedtime at least 1 hour after L-DOPA/DDCI
PlaceboDrug
Capsule of to matching placebo, Oral. Swallow whole with water, once daily at bedtime at least 1 hour after L-DOPA/DDCI
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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). Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Up to 1-year.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jul 2021
- Study start31 May 2021
- Primary completion11 Jan 2023
- Study completion26 Jan 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ParkinsonStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 410 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bial - Portela C S.A.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04978597
- Sponsor's protocol ID
- BIA-91067-303
- Other IDs
- 2020-005011-52
- Acronym
- EPSILON
- Status last verified
- Mar 2025
- First submitted
- 5 Jul 2021
- Last updated
- 12 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III, Double-Blind, Randomized, Placebo-Controlled and Parallel-Group Study to Evaluate the Efficacy and Safety of Opicapone, as Add-on to Stable Levodopa (L-DOPA) Plus a Dopa Decarboxylase Inhibitor (DDCI) Therapy in Early Idiopathic Parkinson's Disease Patients, With an Open-Label Extension
- ClinicalTrials.gov ID
- NCT04978597
- Acronym / sponsor ID
- EPSILON / BIA-91067-303
- Conditions
- Parkinson
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 410 participants (actual)
- Lead sponsor
- Bial - Portela C S.A.Industry (pharma, biotech, devices)
- Study start
- 31 May 2021 (actual)
- Primary completion
- 11 Jan 2023 (actual)
- Study completion
- 26 Jan 2024 (actual)
- First posted
- 27 Jul 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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').
Detailed description
This is a Phase III study to evaluate the efficacy and safety of OPC in subjects with early idiopathic PD receiving treatment with L DOPA plus a DDCI, and who are without signs of any motor complication (consisting of fluctuations in the motor response and/or involuntary movements or dyskinesias).
After a screening period of up to 4 weeks, eligible subjects will be randomized into 1 of 2 treatment arms (OPC 50 mg, or placebo) in a 1:1 ratio, and enter a 24-week placebo-controlled, parallel-group, double blind period.
At the end of the double-blind period, subjects may enter an additional 1-year, open-label period, at the discretion of both the Investigator and subject, in which all subjects will be treated with OPC 50 mg.
A Post-study Visit (PSV) will be performed approximately 2 weeks after the End of Study Visit (EOS) or Early Discontinuation Visit (EDV).
Study treatment will be administered in combination with existing treatment of L-DOPA/DDCI.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Opicapone | Experimental | Drug: Opicapone 50 mgOPC 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). |
| Matching placebo | Placebo comparator | Drug: PlaceboMatching 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). |
Who may qualify
- Ages
- 30 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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).
Key exclusion criteria (23 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Opicapone 50 mgCapsule, 50 mg, Oral. Swallow whole with water, once daily at bedtime at least 1 hour after L-DOPA/DDCI | Drug | Opicapone |
| PlaceboCapsule of to matching placebo, Oral. Swallow whole with water, once daily at bedtime at least 1 hour after L-DOPA/DDCI | Drug | Matching placebo |
Primary outcome
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
Time frame: Up to 24 weeks
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.
Change from open-label baseline (Visit 9) to the end of the open-label period (Visit 15) in MDS-UPDRS Part IV total score.
Time frame: Up to 1-year.
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Mar 2025.
- EU Clinical Trials RegisterLink provided by the sponsor.
- Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS)Link provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Opicapone 50 mg in people with Parkinson, run by Bial - Portela C S.A. at 1 site in Bulgaria.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Bulgaria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: Up to 24 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Mar 2025; AzTrials last refreshed its copy on 6 Nov 2026.