OpiCapone Effect on Motor Fluctuations and pAiN (OCEAN)

Randomised, Double-blind, Placebo-controlled, Clinical Study to Evaluate the Effect of Opicapone 50 mg on Parkinson's Disease Patients With End-of-dose Motor Fluctuations and Associated Pain.

The aim of this study is to investigate the efficacy of 50 mg opicapone when administered with the existing treatment of levodopa (L-dopa) plus a dopa decarboxylase inhibitor (DDCI), in Parkinson's disease (PD) patients with end-of-dose motor fluctuations and associated pain

Study Overview

• Status: Completed
• Conditions: Parkinson Disease
• Intervention / Treatment: Drug: Opicapone 50 mg; Other: Placebo

Detailed Description

This is a randomised, double-blind, placebo-controlled, multi-centre, parallel group, interventional clinical study in PD patients with end-of-dose motor fluctuations and associated pain. The study consists of a 1-week screening period, a 24-week double-blind treatment period and 2 weeks of follow-up period. The duration of treatment for the individual patient is expected to be up to 24 weeks.

• Study Type: Interventional
• Enrollment (Actual): 144
• Phase: Phase 4

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, SE5 9RT
    • The Maurice Wohl Clinical Neuroscience Institute - King's College Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion 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.

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).

Exclusion Criteria:

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, deep 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Other: Placebo; Matching placebo hard capsules. Oral administration, once daily, at least 1 hour before or after the last daily dose of L-dopa/DDCI
Experimental: Opicapone 50 mg; Opicapone (BIA 9-1067)	Drug: Opicapone 50 mg; Opicapone (BIA 9-1067) 50 mg hard capsules. Oral administration, once daily, at least 1 hour before or after the last daily dose of L-dopa/DDCI; Other Names: BIA 9-1067

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Domain 3 (Fluctuation-related Pain) of KING's PARKINSON's DISEASE PAIN SCALE (KPPS)	The KING's PARKINSON's DISEASE PAIN SCALE (KPPS) evaluates the burden (global and bedside) and characterises various phenotypes of pain in Parkinson's disease. The investigator will complete the questionnaire by interviewing the patient about seven domains and answering to 14 items. The questionnaire will be fill out on Visit 1, Visit 2b/Baseline, Visit 4, Visit 5 and Visit 6/EDV Domain 3 assesses fluctuation-related pain (score range: 0 - 36). Higher score values indicate higher levels of pain.	The questionnaire will be fill out on Visit 1 (Day -7 ±2), Visit 2b/Baseline (Day 1), Visit 4 (Day 29 (±2)), Visit 5 (Day 85 (±4)) and Visit 6/Early Discontinuation Visit (EDV) (Day 169 (±4)) - Up to 24 weeks

Collaborators and Investigators

• Sponsor: Bial - Portela C S.A.
• Investigators: Principal Investigator: Kallol Ray Chaudhuri, MD, DSc, King's College Hospital NHS Trust

Publications and helpful links

Helpful Links

• King's Parkinson's Disease Pain Scale

Study record dates

Study Major Dates

• Study Start (Actual): February 25, 2021
• Primary Completion (Actual): February 16, 2024
• Study Completion (Actual): February 16, 2024

Study Registration Dates

• First Submitted: July 27, 2021
• First Submitted That Met QC Criteria: July 27, 2021
• First Posted (Actual): August 3, 2021

Study Record Updates

• Last Update Posted (Actual): March 28, 2025
• Last Update Submitted That Met QC Criteria: March 17, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Synucleinopathies; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; Movement Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Parkinson Disease; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antiparkinson Agents; Anti-Dyskinesia Agents; Catechol O-Methyltransferase Inhibitors; Opicapone
• Other Study ID Numbers: BIA-91067-404; 2020-001175-32 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No