Multicentre Study in Four Parallel Groups of Parkinson's Disease (PD) Patients

Multicentre, Double-blind, Randomised, Placebo-controlled Study in Four Parallel Groups of PD Patients Treated With Standard-release Levodopa/Carbidopa 100/25 mg (Sinemet®) or Levodopa/Benserazide 100/25 mg (Madopar®/Restex®) and With Motor Fluctuations ("Wearing-off" Phenomenon)

The purpose of this study is to investigate the tolerability and the effect of BIA 9-1067 at steady-state on the levodopa pharmacokinetics in Parkinson's Disease (PD) patients treated with levodopa/dopa-decarboxylase inhibitor.

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

Multicentre, double-blind, randomised, placebo-controlled study in four parallel groups of PD patients treated with standard-release levodopa/carbidopa 100/25 mg (Sinemet®) or levodopa/benserazide 100/25 mg (Madopar®/Restex®) and with motor fluctuations ("wearing-off" phenomenon)

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• Romania
  • Brasov, Romania, 500 283
    • Department of Neurology C.M.D.T.A. NEOMED
  • Bucharest, Romania, 024 092
    • Department of Neurology-Quantum Medical Center
  • Craiova, Romania, 200 642
    • Clinica de Medicina Fizica si Recuperare Medicala-Spitalul Clinic Judetean de Urgenta Craiova
• Ukraine
  • Dnipropetrovsk, Ukraine, 49027
    • Ukrainian State Scientific Research Institute of Medical and Social Problems of Disability, Department of Neurology and Adjustment Conditions
  • Kharkiv, Ukraine, 61068
    • Department No. 23 of Communal setting of medical care Kharkiv's regional clinical psychiatric hospital No. 3,
  • Kharkiv, Ukraine, 61068
    • Department of Neuroinfections and multiple sclerosis, SI "Institute of Neurology, Psychiatry and Narcology of AMS of Ukraine
  • Kyiv, Ukraine, 04114
    • Department of Clinical Physiology and Pathology of Extrapyramidal Nervous System SI "Institute of Gerontology, AMS Ukraine"

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 28 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

At screening (admission to the baseline period):

• Male or female of non-childbearing potential (by reason of surgery or postmenopausal);
• Age ≥ 30 years;
• 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;
• Modified Hoehn and Yahr stage of less than 5 in the "off" state; mean duration of "off" state ≥ 1.5 h during waking hours (based on historical information);
• Results of clinical laboratory tests acceptable by the investigator (not clinically significant for the well-being of the patient or for the purpose of the study);
• Able and willing to give written informed consent.

At randomisation (completion of the baseline period):

• Been treated with a stable regimen of 3 to 8 doses per day of standard-release levodopa/carbidopa 100/25 mg (Sinemet®) or levodopa/benserazide 100/25 mg (Madopar®/Restex®) for at least 1 week prior to randomisation;
• Mean duration of "off" state ≥ 1.5 h during waking hours (average of recordings of last 3 evaluable days on patient's diary);
• Concomitant anti-Parkinsonian medication (other than apomorphine, entacapone or tolcapone) in stable doses for at least 4 weeks prior to admission.

Exclusion Criteria:

At screening (admission to the baseline period):

• Non-idiopathic parkinsonism (atypical parkinsonism, symptomatic parkinsonism, Parkinson-plus syndrome);
• 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 2 weeks prior to admission;
• Treated with any investigational product within 1 month prior to admission (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 patient (e.g., hepatic impairment) or related to the study conditions;
• A test positive for the HIV-1 or HIV-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 admission;
• Pregnant, breast-feeding or of childbearing potential;
• Other condition or circumstance that, in the opinion of the investigator, may compromise the patient's ability to comply with the study protocol.

At randomisation (completion of the baseline period):

• Treated with levodopa/DDCI in a 10:1 ratio or in a controlled-release formulation during the baseline period;
• Treated with apomorphine during the baseline period;
• A clinically relevant ECG abnormality.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; PLC, Placebo Levodopa/Carbidopa combination were given to half of the volunteers and Levodopa/Benzerazide to the other half	Drug: Placebo; once-daily; 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®
Experimental: BIA 9-1067 - 5 mg; 5 mg BIA 9-1067 (OPC, Opicapone) Levodopa/Carbidopa combination were given to half of the volunteers and Levodopa/Benzerazide to the other half	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 - 5 mg single-dose; Other Names: OPC, Opicapone; Drug: BIA 9-1067; BIA 9-1067 - 15 mg single-dose; Other Names: OPC, Opicapone; Drug: BIA 9-1067; BIA 9-1067 - 30 mg single-dose; Other Names: OPC, Opicapone
Experimental: BIA 9-1067 - 15 mg; 15 mg BIA 9-1067 (OPC, Opicapone) Levodopa/Carbidopa combination were given to half of the volunteers and Levodopa/Benzerazide to the other half	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 - 5 mg single-dose; Other Names: OPC, Opicapone; Drug: BIA 9-1067; BIA 9-1067 - 15 mg single-dose; Other Names: OPC, Opicapone; Drug: BIA 9-1067; BIA 9-1067 - 30 mg single-dose; Other Names: OPC, Opicapone
Experimental: BIA 9-1067 - 30 mg; 30 mg BIA 9-1067 (OPC, Opicapone) Levodopa/Carbidopa combination were given to half of the volunteers and Levodopa/Benzerazide to the other half	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 - 5 mg single-dose; Other Names: OPC, Opicapone; Drug: BIA 9-1067; BIA 9-1067 - 15 mg single-dose; Other Names: OPC, Opicapone; Drug: BIA 9-1067; BIA 9-1067 - 30 mg single-dose; Other Names: OPC, Opicapone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax - Observed Maximum Concentration	Baseline period - to be switched respectively to standard-release levodopa/carbidopa 100/25 mg (Sinemet®) or levodopa/benserazide 100/25 mg (Madopar®/Restex®) and to adjust the number of daily doses. Test Period - After the baseline period during the 21 to 28 days	28 days
Tmax - Time to Observed Maximum Concentration	Baseline period - to be switched respectively to standard-release levodopa/carbidopa 100/25 mg (Sinemet®) or levodopa/benserazide 100/25 mg (Madopar®/Restex®) and to adjust the number of daily doses. Test Period - After the baseline period during the 21 to 28 days	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC0-6 - Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to to 6 h Postdose (AUC [0-6])	Baseline period - to be switched respectively to standard-release levodopa/carbidopa 100/25 mg (Sinemet®) or levodopa/benserazide 100/25 mg (Madopar®/Restex®) and to adjust the number of daily doses. Test Period - After the baseline period during the 21 to 28 days	28 days

Collaborators and Investigators

• Sponsor: Bial - Portela C S.A.

Study record dates

Study Major Dates

• Study Start: February 1, 2010
• Primary Completion (Actual): June 1, 2010
• Study Completion (Actual): June 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): December 24, 2015
• Last Update Submitted That Met QC Criteria: November 23, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Keywords: Parkinson 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-91067-202; 2009-012897-12 (EudraCT Number)