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

Study Overview
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Brief Summary
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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
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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)

Official Title
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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)

Conditions
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Parkinson's Disease

Intervention / Treatment
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* Drug: Placebo
* Drug: BIA 9-1067
* Drug: BIA 9-1067
* Drug: BIA 9-1067
* Drug: Levodopa/Carbidopa
* Drug: Levodopa/Benzerazide


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>PLC, Placebo Levodopa/Carbidopa combination were given to half of the volunteers and Levodopa/Benzerazide to the other half | Drug: Placebo<br>* once-daily<br>* Other names: PLC;Drug: Levodopa/Carbidopa<br>* Levodopa 100 mg Carbidopa 25 mg<br>* Other names: Sinemet;Drug: Levodopa/Benzerazide<br>* Levodopa 100 mg Benzerazide 25 mg<br>* Other names: Madopar®/Restex®;|
| Experimental: BIA 9-1067 - 5 mg<br>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: BIA 9-1067<br>* BIA 9-1067 - 5 mg single-dose<br>* Other names: OPC, Opicapone;Drug: Levodopa/Carbidopa<br>* Levodopa 100 mg Carbidopa 25 mg<br>* Other names: Sinemet;Drug: Levodopa/Benzerazide<br>* Levodopa 100 mg Benzerazide 25 mg<br>* Other names: Madopar®/Restex®;|
| Experimental: BIA 9-1067 - 15 mg<br>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: BIA 9-1067<br>* BIA 9-1067 - 15 mg single-dose<br>* Other names: OPC, Opicapone;Drug: Levodopa/Carbidopa<br>* Levodopa 100 mg Carbidopa 25 mg<br>* Other names: Sinemet;Drug: Levodopa/Benzerazide<br>* Levodopa 100 mg Benzerazide 25 mg<br>* Other names: Madopar®/Restex®;|
| Experimental: BIA 9-1067 - 30 mg<br>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: BIA 9-1067<br>* BIA 9-1067 - 30 mg single-dose<br>* Other names: OPC, Opicapone;Drug: Levodopa/Carbidopa<br>* Levodopa 100 mg Carbidopa 25 mg<br>* Other names: Sinemet;Drug: Levodopa/Benzerazide<br>* Levodopa 100 mg Benzerazide 25 mg<br>* Other names: Madopar®/Restex®;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Parkinson Disease, BIA 9-1067