Efficacy and Safety of BIA 9-1067 in Idiopathic Parkinson's Disease Patients With "Wearing-off" Phenomenon

Inclusion Criteria

V1 (Screening, up to 14 days before V2)

• Able to comprehend and willing to sign an informed consent form.
• Male and female subjects between 30 and 83 years old, inclusive.
• Diagnosed with idiopathic PD according to the UK Parkinson's Disease Society Brain Bank Clinical Diagnostic Criteria for at least 3 years.
• Disease severity Stages I-III (modified Hoehn &Yahr staging) at ON.
• Treated with L-DOPA/DDCI for at least 1 year with clear clinical improvement as per investigator's judgment.
• Treated with 3 to 8 daily doses of L-DOPA/DDCI, which can include a slow-release formulation.
• On a stable regimen of L-DOPA/DDCI and other anti-PD drugs for at least 4 weeks before screening.
• Signs of "wearing-off" phenomenon (end-of-dose deterioration) for a minimum of 4 weeks before screening, 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 the investigator's judgment).
• Able to keep reliable diaries of motor fluctuations (alone or with family/caregiver assistance).
• Amenorrheic for at least 1 year or surgically sterile for at least 6 months before screening. Females of childbearing potential must be using an effective non-hormonal contraceptive method.

V2 (Randomisation, Day 0)

• Have filled-in self-rating diary charts in accordance with the diary chart instructions and with ≤ 3 errors per day.
• 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 the self-rating diary for at least 2 of the 3 days preceding V2.
• Results of the screening laboratory tests are considered acceptable by the investigator (i.e. not clinically relevant for the well-being of the subject or for the purpose of the study).

Exclusion Criteria

V1 (Screening, up to 14 days before V2)

• Non-idiopathic PD (atypical parkinsonism, secondary [acquired or symptomatic] parkinsonism, Parkinson-plus syndrome).
• Dyskinesia disability score > 3 in the Unified Parkinson's Disease Rating Scale (UPDRS) Sub-section IV A, item 33.
• Severe and/or unpredictable OFF periods.
• Treatment with prohibited medication: tolcapone, neuroleptics, venlafaxine, monoamine oxidase inhibitors (except selegiline up to 10 mg/day in oral formulation or 1.25 mg/day in buccal absorption formulation or rasagiline up to 1 mg/day), or antiemetics with antidopaminergic action (except domperidone) within the month before screening.
• Previous use of entacapone.
• Treatment with apomorphine, alpha-methyldopa, or reserpine within the month before screening or likely to be needed at any time during the study.
• Dosage change of concomitant anti-PD medication within 4 weeks of screening.
• Previous or planned (during the entire study duration, including the OL period) deep brain stimulation.
• Previous stereotactic surgery (e.g. pallidotomy, thalamotomy) for PD or with planned stereotactic surgery during the study period.
• Any IMP 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 assessments.
• Past (within the past year) or present history of suicidal ideation or suicide attempts.
• Current or previous (within the past year) diagnosis of major depressive disorder, mania, bipolar disorder, psychosis, dysthymia, generalised anxiety disorder, alcohol or substance abuse excluding caffeine or nicotine, impulse control disorders (e.g. pathological gambling), dementia or eating disorders according to Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision (DSM-IV) American Psychiatric Association, 2000 criteria, as determined by the investigator.
• A clinically relevant electrocardiogram (ECG) abnormality (relevance should be assessed by a cardiologist if needed).
• Current evidence of unstable cardio