Efficacy and safety of BIA 9-1067 in idiopathic Parkinson’s disease patients with wearing-off” phenomenon treated with levodopa plus a dopa decarboxylase inhibitor (DDCI): a double-blind, randomised, placebo-controlled, parallel-group, multicentre clinical study. - BIPARK STUDY II

Phase 1

• Conditions: Idiopathic Parkinson's Disease; MedDRA version: 12.1Level: LLTClassification code 10061536Term: Parkinson's disease

• Registration Number: EUCTR2010-022366-27-BE
• Lead Sponsor: BIAL Portela & Cª, S.A.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-02-01
• Last Update Posted: 21 August 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 405

Inclusion Criteria

V1 (Screening, up to 14 days before V2)
1.Able to comprehend and willing to sign an informed consent form.
2.Male and female subjects between 30 and 83 years old, inclusive.
3.Diagnosed with idiopathic PD according to the UK Parkinson’s Disease Society Brain Bank Clinical Diagnostic Criteria for at least 3 years.
4.Disease severity Stages I-III (modified Hoehn &Yahr staging) at ON.
5.Treated with L-DOPA/DDCI for at least 1 year with clear clinical improvement, as per investigator’s judgment.
6.Treated with 3 to 8 daily doses of L-DOPA/DDCI, which can include a slow-release formulation.
7.On a stable regimen of L-DOPA/DDCI and other anti-PD drugs for at least 4 weeks before screening.
8.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).
9.Able to distinguish their own motor states and able to keep reliable diaries of motor fluctuations, alone or with family/caregiver assistance (based on the investigator’s judgment).
10.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)
11.Have filled-in self-rating diary charts in accordance with the diary chart instructions and with =3 errors per day, in the 3 days preceding V2.
12.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 2 of the 3-day self-rating diary charts for the 3 days preceding V2.
13.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).

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

V1 (Screening, up to 14 days before V2)
1.Non-idiopathic PD (atypical parkinsonism, secondary [acquired or symptomatic] parkinsonism, Parkinson-plus syndrome).
2.Dyskinesia disability score >3 in the Unified Parkinson’s Disease Rating Scale (UPDRS) Sub-section IV A, item 33.
3.Severe and/or unpredictable OFF periods.
4.Treatment with prohibited medication: entacapone, tolcapone, neuroleptics, venlafaxine, monoamine oxidase (MAO) 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.
5.Treatment with apomorphine, alpha-methyldopa, or reserpine within the month before screening or likely to be needed at any time during the study.
6.Dosage change of concomitant anti-PD medication within 4 weeks of screening.
7.Previous or planned (during the entire study duration, including the OL period) deep brain stimulation.
8.Previous stereotactic surgery (e.g. pallidotomy, thalamotomy) for PD or with planned stereotactic surgery during the study period.
9.Any IMP within the 3 months (or within 5 half-lives, whichever is longer) before screening.
10.Any medical condition that might place the subject at increased risk or interfere with assessments.
11.Past (within the past year) or present history of suicidal ideation or suicide attempts.
12.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.
13.A clinically relevant electrocardiogram (ECG) abnormality (relevance should be assessed by a cardiologist if needed).
14.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).
15.Prior renal transplant or current renal dialysis.
16.Pheochromocytoma, paraganglioma or other catecholamine secretive neoplasm.
17.Known hypersensitivity to the ingredients of IMPs used.
18.History of neuroleptic malignant syndrome (NMS) or NMS-like syndromes, or non-traumatic rhabdomyolysis.
19.Malignancy within past 5 years which in the investigator’s opinion would exclude the subject from the study, except for basal cell carcinoma that has been treated
20.Unstable active narrow-angle or unstable wide-angle glaucoma.
21.History of or current evidence of any relevant disease in the context of this study, i.e. with respect to the safety of the subject or related to the study conditions, e.g. which may influence the absorption or metabolism (such as a relevant liver disease) of the IMP.
22.Pregnant or breastfeeding.
V2 (Randomisation, Day 0)
23.Any abnormality in the liver enzymes (alanine aminotransferase and/or aspartate aminotransferase) >2 times the upper limit of the normal range, in the scree

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified