Idiopathic Parkinson's disease
Conditions
Interventions
placebo group:Once nightly. Administer the investigational medicinal product at least 1 hour after the last bedtime dose of L-Dopa/DDCI. A fasting period of at least 1 hour is required both before and
Opicapone 25mg group:Once nightly. Administer the investigational medicinal product at least 1 hour after the last bedtime dose of L-Dopa/DDCI. A fasting period of at least 1 hour is required both bef
Opicapone 50 mg group:Once nightly. Administer the investigational medicinal product at least 1 hour after the last bedtime dose of L-Dopa/DDCI. A fasting period of at least 1 hour is required both be
Sponsors
Ruijin Hospital, Shanghai Jiaotong University School of Medicine
Eligibility
Sex/Gender
All
Age
30 Years to 80 Years
Inclusion criteria
Inclusion criteria: 1. Screening Inclusion Criteria: (1) Able to understand and voluntarily sign the informed consent form; (2) Male or female subjects aged 30 to 80 years (inclusive); (3) Diagnosed with idiopathic Parkinson’s disease for at least 3 years in accordance with the 2015 Movement Disorder Society (MDS) Clinical Diagnostic Criteria for Parkinson’s Disease; (4) Hoehn-Yahr Stage I–III during the "ON" state; (5) Receiving L-Dopa/DDCI treatment for at least 1 year (3 to 8 daily doses, including extended-release formulations), with clinically significant improvement in symptoms as judged by the Investigator. For subjects participating in the PK study, immediate-release formulations shall be used (with or without extended-release formulations, 3 to 6 daily doses). The Investigator shall assess that administration per protocol requirements during the levodopa challenge will not impose significant safety risks to the subject; (6) Receiving stable doses of L-Dopa/DDCI and/or other anti-Parkinsonian medications for at least 4 weeks; (7) Despite optimal anti-Parkinsonian pharmacotherapy as assessed by the Investigator, subjects have experienced at least 4 weeks of wearing-off (worsening end-of-dose deterioration), with daily OFF time of at least 1.5 hours during waking hours (excluding OFF time prior to the first morning dose); (8) Able to recognize personal motor status and accurately record motor fluctuations in the subject diary card (self-completed and/or completed with assistance from family/caregivers): 2. Randomisation Inclusion Criteria: (1) Perform self-assessment and maintain reasonably accurate records for 3 days prior to Visit 2 in accordance with the subject diary card instructions (=3 recording errors per day); (2) Reconfirm based on completed subject diary cards that the subject has daily OFF time of at least 1.5 hours during waking hours (excluding OFF time prior to the first morning dose).
Exclusion criteria
Exclusion criteria: 1. Screening Exclusion Criteria: (1) Dyskinesia-related score > 3 based on Part IV-A of the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS); (2) History of severe and/or unpredictable OFF episodes; (3) Significant history of cardiovascular and cerebrovascular diseases, including but not limited to: 1) The subject had a history of myocardial infarction, coronary angioplasty or bypass surgery, cardiac valve surgery, clinically significant unstable arrhythmia, unstable angina, transient ischaemic attack, cerebrovascular accident within 6 months prior to screening (except for silent lacunar infarction and/or cerebral microbleeds only identified by imaging, which are judged by the Investigator not to affect subject safety or the evaluation of efficacy and safety of the investigational product); 2) Congestive heart failure classified as New York Heart Association (NYHA) Class III or IV; 3) Uncontrolled moderate to severe hypertension (systolic blood pressure >= 160 mmHg and/or diastolic blood pressure >= 100 mmHg). (4) Electrocardiogram abnormalities deemed by the Investigator to compromise subject safety or confound safety assessment of the investigational product; (5) Unstable and rapidly progressive renal disease; (6) Active liver disease at screening; (7) Subjects with immunodeficiency considered by the Investigator to affect subject safety or safety evaluation of the investigational product, such as recipients of organ transplantation or subjects diagnosed with human immunodeficiency virus infection; (8) History of malignant tumour within the past 5 years (basal cell carcinoma that has been cured is excluded); (9) History of phaeochromocytoma, paraganglioma or other catecholamine-secreting tumours; (10) History of major depression, anxiety or other clinically significant psychiatric disorders; (11) History of neuroleptic malignant syndrome (NMS), NMS-like syndrome or non-traumatic rhabdomyolysis; (12) History of suicidal ideation or suicide attempt within the past year or current presentation (including actual attempts, interrupted attempts or unsuccessful attempts); (13) Dementia or moderate and above cognitive impairment; Part 1.1 cognitive impairment score >= 3 on the UPDRS at screening; (14) Unstable active narrow-angle or open-angle glaucoma; (15) History of alcohol abuse and substance abuse: history of substance abuse within 5 years prior to screening (repeated excessive use of dependent drugs or substances unrelated to medical purposes, including addictive and habitual drugs resulting in physical and psychological dependence) and history of alcohol dependence [chronic heavy alcohol consumption leading to physical and psychological dependence; weekly alcohol intake >14 units for males and >7 units for females (1 unit of alcohol = 360 mL beer or 45 mL 40% proof spirits or 150 mL wine)]; (16) The Investigator judges that the subject is at risk of hypersensitivity or intolerance to the investigational product; (17) Received the following medicinal products within 1 month prior to screening: entacapone, tolcapone, neuroleptics, serotonin and norepinephrine reuptake inhibitors (e.g., venlafaxine, duloxetine), monoamine oxidase inhibitors (except selegiline 5–10 mg oral daily or 1.25 mg orally disintegrating daily, rasagiline 0.5–1 mg oral daily) or antidopaminergic antiemetics (domperidone excluded); (18) Received within 1 month prior to screening or likely to receive during the study the following medi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change from baseline to Weeks 14 to 16 in absolute OFF-time recorded in the subject diaries.; | — |
Secondary
| Measure | Time frame |
|---|---|
| Response rates of On-time and OFF-time recorded in the subject diaries at the end of treatment; Change from baseline to Weeks 14 to 16 in ON-time (including total ON-time, ON-time without dyskinesia, ON-time with non-troublesome dyskinesia, and ON-time with troublesome dyskinesia) recorded in the subject diaries;MDS-UPDRS total score [sum of Part I (ON-time), Part II (ON-time), and Part III (ON-time)] and sub-score, including Part I (ON-time), Part II (ON-time and OFF-time), Part III (ON-time), and Part IV (Motor complications: A, B, and C) and change from baseline to Week 14 to 16 in Hoehn & Yahr; Change from baseline in Schwab & England Activities of Daily Living Scale ("On time" and "Off time") at Weeks 14–16;Investigator and subject assessments of overall improvement in PD.; | — |
Countries
China
Contacts
Public ContactShengdi Chen
Ruijin Hospital, Shanghai Jiaotong University School of Medicine
Outcome results
None listed