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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Bial - Portela C S.A.
ClinicalTrials.gov Identifier:
NCT01568073
First received: March 29, 2012
Last updated: June 23, 2014
Last verified: June 2014
  Purpose

This study aims to demonstrate the efficacy and safety of BIA 9-1067, compared with entacapone or placebo, when administered with the existing treatment of L-DOPA plus a Dopa Decarboxylase Inhibitor (DDCI), in patients with Parkinson's Disease (PD) and end-of-dose motor fluctuations.


Condition Intervention Phase
Parkinson's Disease
Drug: BIA 9-1067
Drug: Entacapone
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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- and Active-controlled, Parallel-group, Multicentre Clinical Study

Resource links provided by NLM:


Further study details as provided by Bial - Portela C S.A.:

Primary Outcome Measures:
  • Efficacy of 3 BIA 9-1067 (5 mg, 25 mg, and 50 mg) compared with 200 mg of entacapone or placebo, when administered with the existing treatment of L-DOPA plus a DDCI, in patients with PD and end-of-dose motor fluctuations [ Time Frame: 14-15 weeks ] [ Designated as safety issue: No ]
    The primary efficacy variable will be the change from baseline in absolute OFF-time at the end of the DB period.


Secondary Outcome Measures:
  • UPDRS Sections I (ON), II (ON and OFF), and III (ON) [ Time Frame: 14-15 weeks ] [ Designated as safety issue: No ]
  • Parkinson's Disease Sleep Scale (PDSS) [ Time Frame: 14-15 weeks ] [ Designated as safety issue: No ]
  • Non-motor Symptoms Scale (NMSS) [ Time Frame: 14-15 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 550
Study Start Date: March 2011
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BIA 9-1067 Drug: BIA 9-1067
5, 25 and 50 mg of BIA 9-1067 (once-daily)
Active Comparator: Entacapone Drug: Entacapone
200 mg entacapone (concomitantly with each L-dopa/DDCI dose)
Placebo Comparator: Placebo Drug: Placebo
200 mg

Detailed Description:

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- and active-controlled, parallel-group, multicentre clinical study.

  Eligibility

Ages Eligible for Study:   30 Years to 83 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 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 haemodynamic repercussions as symptomatic bradycardia or syncope).
  • Prior renal transplant or current renal dialysis.
  • Pheochromocytoma, paraganglioma, or other catecholamine secretive neoplasm.
  • Known hypersensitivity to the ingredients of IMPs used.
  • History of neuroleptic malignant syndrome (NMS) or NMS-like syndromes, or non-traumatic rhabdomyolysis.
  • History of or current cancer disease, which in the investigator's opinion would exclude the subject from the study (e.g. melanoma, prostate cancer).
  • Unstable active narrow-angle or unstable wide-angle glaucoma.
  • 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.
  • Pregnant or breastfeeding. V2 (Randomisation, Day 0)
  • Any abnormality in the liver enzymes (alanine aminotransferase and/or aspartate aminotransferase) > 2 times the upper limit of the normal range, in the screening laboratory tests results.
  • Plasma sodium < 130 mmol/L, white blood cell count < 3000 cells/mm3, or any other relevant clinical laboratory abnormality in the screening laboratory tests results that, in the investigator's opinion, may compromise the subject's safety.
  • Inadequate compliance to concomitant L-DOPA/DDCI and other anti-PD drugs during the Screening period.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01568073

Locations
Portugal
Bial - Portela & Cª, S.A.
S. Mamede do Coronado, Portugal, 4745-457
Sponsors and Collaborators
Bial - Portela C S.A.
Investigators
Principal Investigator: Joaquim Ferreira, MD, PhD Centro Hospitalar de Lisboa Norte, EPE - Hospital de Staª Maria-Centro de Estudos Egas Moniz
  More Information

No publications provided

Responsible Party: Bial - Portela C S.A.
ClinicalTrials.gov Identifier: NCT01568073     History of Changes
Other Study ID Numbers: BIA-91067-301, 2010-021860-13
Study First Received: March 29, 2012
Last Updated: June 23, 2014
Health Authority: Portugal: National Pharmacy and Medicines Institute

Keywords provided by Bial - Portela C S.A.:
Parkinson
PD
Wearing-off
Levodopa/DDCI

Additional relevant MeSH terms:
Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Entacapone
Antiparkinson Agents
Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014