Multicentre Study in Four Parallel Groups of Parkinson's Disease (PD) Patients
- Conditions
- Parkinson's Disease
- Interventions
- Registration Number
- NCT01568047
- Lead Sponsor
- Bial - Portela C S.A.
- Brief Summary
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.
- 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)
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 40
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.
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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description BIA 9-1067 - 5 mg BIA 9-1067 5 mg BIA 9-1067 (OPC, Opicapone) Levodopa/Carbidopa combination were given to half of the volunteers and Levodopa/Benzerazide to the other half BIA 9-1067 - 5 mg Levodopa/Carbidopa 5 mg BIA 9-1067 (OPC, Opicapone) Levodopa/Carbidopa combination were given to half of the volunteers and Levodopa/Benzerazide to the other half BIA 9-1067 - 30 mg Levodopa/Benzerazide 30 mg BIA 9-1067 (OPC, Opicapone) Levodopa/Carbidopa combination were given to half of the volunteers and Levodopa/Benzerazide to the other half Placebo Placebo PLC, Placebo Levodopa/Carbidopa combination were given to half of the volunteers and Levodopa/Benzerazide to the other half Placebo Levodopa/Carbidopa PLC, Placebo Levodopa/Carbidopa combination were given to half of the volunteers and Levodopa/Benzerazide to the other half Placebo Levodopa/Benzerazide PLC, Placebo Levodopa/Carbidopa combination were given to half of the volunteers and Levodopa/Benzerazide to the other half BIA 9-1067 - 5 mg Levodopa/Benzerazide 5 mg BIA 9-1067 (OPC, Opicapone) Levodopa/Carbidopa combination were given to half of the volunteers and Levodopa/Benzerazide to the other half BIA 9-1067 - 15 mg BIA 9-1067 15 mg BIA 9-1067 (OPC, Opicapone) Levodopa/Carbidopa combination were given to half of the volunteers and Levodopa/Benzerazide to the other half BIA 9-1067 - 15 mg Levodopa/Benzerazide 15 mg BIA 9-1067 (OPC, Opicapone) Levodopa/Carbidopa combination were given to half of the volunteers and Levodopa/Benzerazide to the other half BIA 9-1067 - 30 mg BIA 9-1067 30 mg BIA 9-1067 (OPC, Opicapone) Levodopa/Carbidopa combination were given to half of the volunteers and Levodopa/Benzerazide to the other half BIA 9-1067 - 30 mg Levodopa/Carbidopa 30 mg BIA 9-1067 (OPC, Opicapone) Levodopa/Carbidopa combination were given to half of the volunteers and Levodopa/Benzerazide to the other half BIA 9-1067 - 15 mg Levodopa/Carbidopa 15 mg BIA 9-1067 (OPC, Opicapone) Levodopa/Carbidopa combination were given to half of the volunteers and Levodopa/Benzerazide to the other half
- Primary Outcome Measures
Name Time Method Cmax - Observed Maximum Concentration 28 days 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 daysTmax - Time to Observed Maximum Concentration 28 days 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
- Secondary Outcome Measures
Name Time Method AUC0-6 - Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to to 6 h Postdose (AUC [0-6]) 28 days 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
Trial Locations
- Locations (7)
Ukrainian State Scientific Research Institute of Medical and Social Problems of Disability, Department of Neurology and Adjustment Conditions
🇺🇦Dnipropetrovsk, Ukraine
Department of Neuroinfections and multiple sclerosis, SI "Institute of Neurology, Psychiatry and Narcology of AMS of Ukraine
🇺🇦Kharkiv, Ukraine
Department No. 23 of Communal setting of medical care Kharkiv's regional clinical psychiatric hospital No. 3,
🇺🇦Kharkiv, Ukraine
Department of Neurology C.M.D.T.A. NEOMED
🇷🇴Brasov, Romania
Clinica de Medicina Fizica si Recuperare Medicala-Spitalul Clinic Judetean de Urgenta Craiova
🇷🇴Craiova, Romania
Department of Neurology-Quantum Medical Center
🇷🇴Bucharest, Romania
Department of Clinical Physiology and Pathology of Extrapyramidal Nervous System SI "Institute of Gerontology, AMS Ukraine"
🇺🇦Kyiv, Ukraine