Parkinson Disease
Conditions
Brief summary
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
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.
Interventions
OTHERPlacebo
Matching placebo hard capsules. Oral administration, once daily, at least 1 hour before or after the last daily dose of L-dopa/DDCI
DRUGOpicapone 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
Sponsors
Bial - Portela C S.A.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
30 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Domain 3 (Fluctuation-related Pain) of KING's PARKINSON's DISEASE PAIN SCALE (KPPS) | 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 | 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. |
Countries
United Kingdom
Participant flow
Pre-assignment details
A total of 144 patients were enrolled and 19 patients prematurely terminated the trial.
Participants by arm
| Arm | Count |
|---|---|
| Opicapone 50 mg Opicapone (BIA 9-1067)
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 | 59 |
| Placebo Placebo
Placebo: Matching placebo hard capsules. Oral administration, once daily, at least 1 hour before or after the last daily dose of L-dopa/DDCI | 63 |
| Total | 122 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 4 |
| Overall Study | Ineligibility | 3 | 0 |
| Overall Study | Lack of Efficacy | 0 | 2 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Sponsor's discretion | 1 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 1 |
Baseline characteristics
| Characteristic | Total | Placebo | Opicapone 50 mg |
|---|---|---|---|
| Age, Categorical ≥ 18 years - < 65 years | 50 Participants | 29 Participants | 21 Participants |
| Age, Categorical ≥ 65 years - < 85 years | 71 Participants | 34 Participants | 37 Participants |
| Age, Categorical ≥ 85 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Continuous | 66.2 years STANDARD_DEVIATION 9.26 | 65.5 years STANDARD_DEVIATION 9.39 | 66.9 years STANDARD_DEVIATION 9.14 |
| Body mass index (BMI) | 28.65 kg/m^2 STANDARD_DEVIATION 5.011 | 29.10 kg/m^2 STANDARD_DEVIATION 5.079 | 28.16 kg/m^2 STANDARD_DEVIATION 4.934 |
| Childbearing potential No | 55 Participants | 29 Participants | 26 Participants |
| Childbearing potential Yes | 3 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 121 Participants | 62 Participants | 59 Participants |
| Region of Enrollment Czechia | 26 participants | 10 participants | 16 participants |
| Region of Enrollment Germany | 7 participants | 5 participants | 2 participants |
| Region of Enrollment Italy | 10 participants | 1 participants | 9 participants |
| Region of Enrollment Poland | 28 participants | 14 participants | 14 participants |
| Region of Enrollment Portugal | 18 participants | 11 participants | 7 participants |
| Region of Enrollment Spain | 16 participants | 11 participants | 5 participants |
| Region of Enrollment United Kingdom | 17 participants | 11 participants | 6 participants |
| Sex: Female, Male Female | 58 Participants | 31 Participants | 27 Participants |
| Sex: Female, Male Male | 64 Participants | 32 Participants | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 64 | 0 / 63 |
| other Total, other adverse events | 40 / 64 | 36 / 63 |
| serious Total, serious adverse events | 4 / 64 | 2 / 63 |
Outcome results
Primary
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.
Time frame: 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
Population: A total of 122 (96.1%) patients met the criteria for the full analysis set (FAS) including 59 (92.2%) opicapone 50 mg and 63 (100.0%) placebo patients.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Opicapone 50 mg | Change From Baseline in Domain 3 (Fluctuation-related Pain) of KING's PARKINSON's DISEASE PAIN SCALE (KPPS) | Visit 2b (Day 1) | 17.1 score on a scale | Standard Deviation 5.58 |
| Opicapone 50 mg | Change From Baseline in Domain 3 (Fluctuation-related Pain) of KING's PARKINSON's DISEASE PAIN SCALE (KPPS) | Visit 5 (Day 85 (±4)) - Observed Value | 8.3 score on a scale | Standard Deviation 7.27 |
| Opicapone 50 mg | Change From Baseline in Domain 3 (Fluctuation-related Pain) of KING's PARKINSON's DISEASE PAIN SCALE (KPPS) | Visit 4 (Day 29 (±2)) - Observed Value | 10.5 score on a scale | Standard Deviation 7.92 |
| Opicapone 50 mg | Change From Baseline in Domain 3 (Fluctuation-related Pain) of KING's PARKINSON's DISEASE PAIN SCALE (KPPS) | Visit 5 (Day 85 (±4)) - Change from Baseline | -8.7 score on a scale | Standard Deviation 6.68 |
| Opicapone 50 mg | Change From Baseline in Domain 3 (Fluctuation-related Pain) of KING's PARKINSON's DISEASE PAIN SCALE (KPPS) | Baseline (Day 1) | 17.1 score on a scale | Standard Deviation 5.58 |
| Opicapone 50 mg | Change From Baseline in Domain 3 (Fluctuation-related Pain) of KING's PARKINSON's DISEASE PAIN SCALE (KPPS) | Visit 6 (Day 169 (±4)) - Observed Value | 8.4 score on a scale | Standard Deviation 6.93 |
| Opicapone 50 mg | Change From Baseline in Domain 3 (Fluctuation-related Pain) of KING's PARKINSON's DISEASE PAIN SCALE (KPPS) | Visit 4 (Day 29 (±2)) - Change from Baseline | -6.6 score on a scale | Standard Deviation 7.28 |
| Opicapone 50 mg | Change From Baseline in Domain 3 (Fluctuation-related Pain) of KING's PARKINSON's DISEASE PAIN SCALE (KPPS) | Visit 6 (Day 169 (±4)) - Change from Baseline | -8.8 score on a scale | Standard Deviation 6.85 |
| Opicapone 50 mg | Change From Baseline in Domain 3 (Fluctuation-related Pain) of KING's PARKINSON's DISEASE PAIN SCALE (KPPS) | Visit 1 (Day -7 ±2) | 17.2 score on a scale | Standard Deviation 5.72 |
| Placebo | Change From Baseline in Domain 3 (Fluctuation-related Pain) of KING's PARKINSON's DISEASE PAIN SCALE (KPPS) | Visit 6 (Day 169 (±4)) - Change from Baseline | -9.3 score on a scale | Standard Deviation 6.24 |
| Placebo | Change From Baseline in Domain 3 (Fluctuation-related Pain) of KING's PARKINSON's DISEASE PAIN SCALE (KPPS) | Visit 1 (Day -7 ±2) | 16.7 score on a scale | Standard Deviation 5.18 |
| Placebo | Change From Baseline in Domain 3 (Fluctuation-related Pain) of KING's PARKINSON's DISEASE PAIN SCALE (KPPS) | Visit 2b (Day 1) | 16.9 score on a scale | Standard Deviation 5.2 |
| Placebo | Change From Baseline in Domain 3 (Fluctuation-related Pain) of KING's PARKINSON's DISEASE PAIN SCALE (KPPS) | Baseline (Day 1) | 16.9 score on a scale | Standard Deviation 5.2 |
| Placebo | Change From Baseline in Domain 3 (Fluctuation-related Pain) of KING's PARKINSON's DISEASE PAIN SCALE (KPPS) | Visit 4 (Day 29 (±2)) - Observed Value | 11.0 score on a scale | Standard Deviation 7.51 |
| Placebo | Change From Baseline in Domain 3 (Fluctuation-related Pain) of KING's PARKINSON's DISEASE PAIN SCALE (KPPS) | Visit 4 (Day 29 (±2)) - Change from Baseline | -5.9 score on a scale | Standard Deviation 6.02 |
| Placebo | Change From Baseline in Domain 3 (Fluctuation-related Pain) of KING's PARKINSON's DISEASE PAIN SCALE (KPPS) | Visit 5 (Day 85 (±4)) - Observed Value | 9.3 score on a scale | Standard Deviation 5.73 |
| Placebo | Change From Baseline in Domain 3 (Fluctuation-related Pain) of KING's PARKINSON's DISEASE PAIN SCALE (KPPS) | Visit 5 (Day 85 (±4)) - Change from Baseline | -7.6 score on a scale | Standard Deviation 6.13 |
| Placebo | Change From Baseline in Domain 3 (Fluctuation-related Pain) of KING's PARKINSON's DISEASE PAIN SCALE (KPPS) | Visit 6 (Day 169 (±4)) - Observed Value | 7.5 score on a scale | Standard Deviation 6.48 |