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

NCT01568073 | Completed Phase 3 Results

• 2 other identifiers: BIA-91067-3012010-021860-13
• Study Type: interventional
• Target: 600
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Parkinson's Disease

Keywords

Parkinson; PD; Wearing-off; Levodopa/DDCI

Outcome Measures

Primary Outcomes (1)

• Efficacy of 3 BIA 9-1067 (5 mg, 25 mg, and 50 mg) Compared With 200 mg of Entacapone or Placebo,

  The primary efficacy variable will be the change from baseline in absolute OFF-time at the end of the DB period, This results refers when administered with the existing treatment of L-DOPA plus a DDCI, in patients with PD and end-of-dose motor fluctuations

  14 to 15 weeks

Secondary Outcomes (3)

• Total UPDRS SCORE (I, II (ON), and III)

  14 to 15 weeks

• Parkinson's Disease Sleep Scale (PDSS)

  14 to 15 weeks

• Non-motor Symptoms Scale (NMSS)

  14 to 15 weeks

Study Arms (3)

BIA 9-1067

EXPERIMENTAL

OPC, Opicapone

Drug: BIA 9-1067; Drug: Levodopa; Drug: Carbidopa; Drug: Benserazide

Entacapone

ACTIVE COMPARATOR

Comtan®; Active comparator

Drug: Entacapone; Drug: Levodopa; Drug: Carbidopa; Drug: Benserazide

Placebo

PLACEBO COMPARATOR

PLC, Placebo

Drug: Placebo; Drug: Levodopa; Drug: Carbidopa; Drug: Benserazide

Interventions

BIA 9-1067 DRUG

5, 25 and 50 mg of BIA 9-1067 (once-daily)

Also known as: OPC, Opicapone

BIA 9-1067

Entacapone DRUG

200 mg entacapone (concomitantly with each L-dopa/DDCI dose)

Also known as: Comtan®

Entacapone

Placebo DRUG

200 mg

Also known as: PLC

Placebo

Levodopa DRUG

Also known as: L-Dopa

BIA 9-1067; Entacapone; Placebo

Carbidopa DRUG

DOPA decarboxylase inhibitor

BIA 9-1067; Entacapone; Placebo

Benserazide DRUG

DOPA decarboxylase inhibitor

BIA 9-1067; Entacapone; Placebo

Eligibility Criteria

• Age: 30 Years - 83 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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).

Sponsors & Collaborators

• Bial - Portela C S.A.: lead

Study Sites (1)

Bial - Portela & Cª, S.A.

S. Mamede Do Coronado, 4745-457, Portugal

Location

Related Publications (2)

• Harrison-Jones G, Green W, Bainbridge J. The Cost-Effectiveness of Opicapone Versus Entacapone as Adjuvant Therapy for Levodopa-Treated Individuals With Parkinson's Disease Experiencing End-of-Dose Motor Fluctuations. Parkinsons Dis. 2025 Sep 11;2025:8408907. doi: 10.1155/padi/8408907. eCollection 2025.

  PMID: 40979212 DERIVED

• Ferreira JJ, Lees A, Rocha JF, Poewe W, Rascol O, Soares-da-Silva P; Bi-Park 1 investigators. Opicapone as an adjunct to levodopa in patients with Parkinson's disease and end-of-dose motor fluctuations: a randomised, double-blind, controlled trial. Lancet Neurol. 2016 Feb;15(2):154-165. doi: 10.1016/S1474-4422(15)00336-1. Epub 2015 Dec 23.

  PMID: 26725544 DERIVED

MeSH Terms

Conditions

Parkinson Disease

Interventions

opicapone; entacapone; Levodopa; Carbidopa; Benserazide

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Dihydroxyphenylalanine; Catecholamines; Amines; Organic Chemicals; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Tyrosine; Methyldopa; Hydrazines

Results Point of Contact

• Title: Head of Clinical Research
• Organization: Bial - Portela & Cª, S.A.

jose.rocha@bial.com

+351 229 866 100

Study Officials

• Joaquim Ferreira, MD, PhD

  Centro Hospitalar de Lisboa Norte, EPE - Hospital de Staª Maria-Centro de Estudos Egas Moniz

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 29, 2012
• First Posted: April 2, 2012
• Study Start: March 1, 2011
• Primary Completion: November 1, 2013
• Study Completion: November 1, 2013
• Last Updated: September 18, 2015
• Results First Posted: January 8, 2015

Record last verified: 2015-09

Locations

PT (1)