A Study to Investigate the Tolerability and Effect of Three Single-dose Regimens of BIA 9-1067

A Double-blind, Randomised, Placebo-controlled, Cross-over Study to Investigate the Tolerability and Effect of Three Single-dose Regimens of BIA 9-1067 on the Levodopa Pharmacokinetics, Motor Response, and Erythrocyte Soluble Catechol-O-methyltransferase Activity in Parkinson's Disease Patients Concomitantly Treated With Levodopa/Dopa-decarboxylase Inhibitor

The purpose of this study is to investigate the effect of BIA 9-1067 on the levodopa pharmacokinetics when administered in combination with immediate release levodopa/carbidopa or levodopa/benserazide in Parkinson's Disease (PD) patients.

Study Overview

• Status: Completed
• Conditions: Parkinson's Disease
• Intervention / Treatment: Drug: Placebo; Drug: Levodopa/Carbidopa; Drug: Levodopa/Benzerazide; Drug: BIA 9-1067; Drug: BIA 9-1067; Drug: BIA 9-1067

Detailed Description

This was a three-centre, double-blind, randomised, placebo-controlled, crossover study with four consecutive single-dose treatment periods in PD patients treated with immediate release 100 mg/25 mg levodopa/carbidopa or 100 mg/25 mg levodopa/benserazide

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• Portugal
  • Lisbon, Portugal, 1649-035
    • Department of Neurology-Hospital de Santa Maria-Faculty of Medicine, University of Lisbon
• Romania
  • Bucharest, Romania, 020125
    • Spitalul Clinic Colentina - Clinica de Neurologie
• Ukraine
  • Kyiv, Ukraine, 04050
    • Department of Neurology- Hospital of the department of medical care of Ministry Internal Affairs of Ukraine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female of non-childbearing potential (by reason of surgery or postmenopausal);
• Aged between 30 and 75 years, inclusive;
• A diagnosis of PD according to the UK PDS Brain Bank diagnostic criteria (bradykinesia and at least one of the following: muscular rigidity, rest tremor and postural instability);
• Predictable signs of end-of-dose deterioration despite "optimal" levodopa/carbidopa or levodopa/benserazide therapy;
• Been treated with a stable regimen of 3 to 8 doses of standard release 100 mg/25 mg levodopa/carbidopa or 100 mg/25 mg levodopa/benserazide per day within at least 1 week prior to randomisation;
• Modified Hoehn and Yahr stage of less than 5 in the off-state;
• Mean duration of OFF stage ≥ 1.5 h during waking hours (based on historical information);
• Concomitant anti-Parkinsonian medication (other than apomorphine, entacapone or tolcapone) in stable doses for at least 4 weeks prior to randomisation;
• Results of clinical laboratory tests acceptable by the investigator (not clinically significant for the well-being of the subject or for the purpose of the study);
• Able and willing to give written informed consent.

Exclusion Criteria:

• Non-idiopathic parkinsonism (atypical parkinsonism, symptomatic parkinsonism, Parkinson-plus syndrome);
• Treated with levodopa/carbidopa or levodopa/benserazide in a 10:1 ratio, or with levodopa/carbidopa in a controlled-release formulation;
• Treated with entacapone, tolcapone, neuroleptics, antidepressants (except serotonin-specific reuptake inhibitors or imipramines [desipramine, imipramine, clomipramine and amitriptyline]), 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 (except domperidone) within 4 weeks prior to randomisation;
• Treated with apomorphine within 7 days prior to randomisation;
• Treated with any investigational product within 2 months prior to randomisation (or within 5 half-lives, whichever is longer);
• A psychiatric or any medical condition that might place him/her at increased risk or interfere with assessments;
• Known hypersensitivity to any of the ingredients of the investigational products;
• A history of abuse of alcohol, drugs or medications within the last 2 years;
• A clinically relevant ECG abnormality;
• A history or current evidence of heart disease, including but not limited to myocardial infarction, angina, congestive heart failure and cardiac arrhythmia;
• Unstable concomitant disease being treated with changing doses of medication;
• A history or current evidence of any relevant disease in the context of this study, i.e., with respect to the safety of the subject (e.g., hepatic or renal impairment) or related to the study conditions;
• A test positive for the human immunodeficiency viruses (HIV) 1 or 2 antibodies, or hepatitis B surface antigen (HBsAg), or hepatitis C antibody (HCVAb);
• Donated blood or received blood or blood products within the 6 months prior to randomisation;
• Pregnant, breast-feeding or of childbearing potential;
• Other condition or circumstance that, in the opinion of the investigator, may compromise the subject's ability to comply with the study protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Sequence A; Treatment Sequence A Period 1 - 25 mg BIA 9-1067 Period 2 - 50 mg BIA 9-1067 Period 3 - 100 mg BIA 9-1067 Period 4 - Placebo Levodopa/Carbidopa combination were given to half of the volunteers and Levodopa/Benzerazide to the other half	Drug: Placebo; single-dose; Other Names: PLC; Drug: Levodopa/Carbidopa; Levodopa 100 mg Carbidopa 25 mg; Other Names: Sinemet; Drug: Levodopa/Benzerazide; Levodopa 100 mg Benzerazide 25 mg; Other Names: Madopar®/Restex®; Drug: BIA 9-1067; BIA 9-1067 - 25 mg single-dose; Other Names: OPC, Opicapone; Drug: BIA 9-1067; BIA 9-1067 - 50 mg single-dose; Other Names: OPC, Opicapone; Drug: BIA 9-1067; BIA 9-1067 - 100 mg single-dose; Other Names: OPC, Opicapone
Experimental: Treatment Sequence B; Treatment Sequence B Period 1 - Placebo Period 2 - 25 mg BIA 9-1067 Period 3 - 50 mg BIA 9-1067 Period 4 - 100 mg BIA 9-1067 Levodopa/Carbidopa combination were given to half of the volunteers and Levodopa/Benzerazide to the other half	Drug: Placebo; single-dose; Other Names: PLC; Drug: Levodopa/Carbidopa; Levodopa 100 mg Carbidopa 25 mg; Other Names: Sinemet; Drug: Levodopa/Benzerazide; Levodopa 100 mg Benzerazide 25 mg; Other Names: Madopar®/Restex®; Drug: BIA 9-1067; BIA 9-1067 - 25 mg single-dose; Other Names: OPC, Opicapone; Drug: BIA 9-1067; BIA 9-1067 - 50 mg single-dose; Other Names: OPC, Opicapone; Drug: BIA 9-1067; BIA 9-1067 - 100 mg single-dose; Other Names: OPC, Opicapone
Experimental: Treatment Sequence C; Treatment Sequence C Period 1 - 100 mg BIA 9-1067 Period 2 - Placebo Period 3 - 25 mg BIA 9-1067 Period 4 - 50 mg BIA 9-1067 Levodopa/Carbidopa combination were given to half of the volunteers and Levodopa/Benzerazide to the other half	Drug: Placebo; single-dose; Other Names: PLC; Drug: Levodopa/Carbidopa; Levodopa 100 mg Carbidopa 25 mg; Other Names: Sinemet; Drug: Levodopa/Benzerazide; Levodopa 100 mg Benzerazide 25 mg; Other Names: Madopar®/Restex®; Drug: BIA 9-1067; BIA 9-1067 - 25 mg single-dose; Other Names: OPC, Opicapone; Drug: BIA 9-1067; BIA 9-1067 - 50 mg single-dose; Other Names: OPC, Opicapone; Drug: BIA 9-1067; BIA 9-1067 - 100 mg single-dose; Other Names: OPC, Opicapone
Experimental: Treatment Sequence D; Treatment Sequence D Period 1 - 50 mg BIA 9-1067 Period 2 - 100 mg BIA 9-1067 Period 3 - Placebo Period 4 - 25 mg BIA 9-1067 Levodopa/Carbidopa combination were given to half of the volunteers and Levodopa/Benzerazide to the other half	Drug: Placebo; single-dose; Other Names: PLC; Drug: Levodopa/Carbidopa; Levodopa 100 mg Carbidopa 25 mg; Other Names: Sinemet; Drug: Levodopa/Benzerazide; Levodopa 100 mg Benzerazide 25 mg; Other Names: Madopar®/Restex®; Drug: BIA 9-1067; BIA 9-1067 - 25 mg single-dose; Other Names: OPC, Opicapone; Drug: BIA 9-1067; BIA 9-1067 - 50 mg single-dose; Other Names: OPC, Opicapone; Drug: BIA 9-1067; BIA 9-1067 - 100 mg single-dose; Other Names: OPC, Opicapone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax - Maximum Plasma Concentration Day 3	Cmax - Maximum plasma concentration (ng/mL)	Day 3
Tmax = Time to Cmax Day 3	tmax = time to Cmax (values are median)	Day 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC0-6 - Area Under the Plasma Concentration-time Curve From Time 0 to 6 Hours Post-dose (Day 3)	AUC0-6 - area under the plasma concentration-time curve from time 0 to 6 hours post-dose (ng.h/mL)	Day 3

Collaborators and Investigators

• Sponsor: Bial - Portela C S.A.
• Investigators: Principal Investigator: Joaquim Ferreira, MD, PhD, Hospital de Santa Maria, Lisbon

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (Actual): February 1, 2010
• Study Completion (Actual): February 1, 2010

Study Registration Dates

• First Submitted: March 29, 2012
• First Submitted That Met QC Criteria: March 30, 2012
• First Posted (Estimate): April 2, 2012

Study Record Updates

• Last Update Posted (Estimate): January 12, 2015
• Last Update Submitted That Met QC Criteria: December 19, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Keywords: Parkinson's Disease; BIA 9-1067
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Dopamine Agents; Antiparkinson Agents; Anti-Dyskinesia Agents; Catechol O-Methyltransferase Inhibitors; Aromatic Amino Acid Decarboxylase Inhibitors; Levodopa; Carbidopa; Opicapone
• Other Study ID Numbers: BIA-91067-201; 2008-003869-72 (EudraCT Number)