A Study of the Pharmacokinetics, Pharmacodynamics, and Safety of Opicapone in Subjects With Parkinson's Disease Taking Levodopa.

Study Overview
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Brief Summary
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This is a phase 1, open-label study to assess the pharmacokinetics, pharmacodynamics, safety, and tolerability of opicapone when administered orally once daily for 14 days as adjunctive therapy to carbidopa/levodopa in subjects with Parkinson's disease.

Official Title
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A Phase 1, Open-Label Study to Assess the Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of Repeated Doses of Opicapone, and Effect on Levodopa Pharmacokinetics in Subjects With Parkinson's Disease

Conditions
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Parkinson Disease

Intervention / Treatment
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* Drug: Opicapone
* Drug: Carbidopa Levodopa


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a clinical diagnosis of idiopathic Parkinson's Disease (PD) for at least 3 years with clear improvement with levodopa treatment Be at a stable dose of maintenance medication(s) for PD, including stable doses of CD/LD Subjects of childbearing potential who do not practice total abstinence must agree to use hormonal or two forms of nonhormonal contraception (dual contraception) consistently during the screening, treatment and follow-up periods of the study Have a body mass index (BMI) of 18 to 40 kg/m2 Have a modified Hoehn and Yahr stage of ≤4 in the OFF state Be able to tolerate an overnight period of 12 hours without CD/LD Be in good general health and expected to complete the clinical study as designed Exclusion Criteria: Are currently pregnant or breastfeeding More than 2 alcoholic beverages daily or more than 14 alcoholic beverages weekly within 7 days of Day -1 or consume any alcohol within 48 hours of Day -1. Have motor fluctuations during the day (ie, effect of levodopa wearing off or having unpredictable off periods), or severe or intolerable levodopa-induced dyskinesia Have had previous exposure to opicapone, or have an allergy, hypersensitivity, or intolerance to opicapone or other COMT inhibitor. Have a history of a medical condition or surgical procedure that might interfere with absorption or metabolism. Have a known history of neuroleptic malignant syndrome Have an unstable medical condition or chronic disease Have taken certain prohibited medications within 28 days of Day -1. Have a known or suspected diagnosis of AIDS, or have tested seropositive for HIV Have hepatitis A or B Have a significant risk of suicidal or violent behavior

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Opicapone once daily with Carbidopa/Levodopa<br>Opicapone administered once daily for 14 days; carbidopa/levodopa administered at set frequency on Study Days 1, 2 & 15 | Drug: Opicapone<br>* catechol-O-methyltransferase (COMT) inhibitor<br>* Other names: BIA 9-1067;Drug: Carbidopa Levodopa<br>* Levodopa: dopamine precursor Carbidopa: DOPA decarboxylase inhibitor<br>* Other names: Sinemet;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic evaluation of opicapone and its metabolites: area under the curve (AUC 0-24) | Area under the plasma concentration versus time curve from 0 to 24 hours for analytes with quantifiable concentrations at 24 hours postdose | up to 19 days | 
| Pharmacokinetic evaluation of opicapone and its metabolites: area under the curve (AUC 0-tlast) | Area under the plasma concentration versus time curve from 0 hour to the time of the last measurable concentration for analytes below the limit of quantification at 24 hours postdose | up to 19 days | 
| Pharmacokinetic evaluation of opicapone and its metabolites: Maximum plasma concentration (Cmax) | Maximum plasma concentration | up to 19 days | 
| Pharmacokinetic evaluation of opicapone and its metabolites: Time to maximum plasma concentration (tmax) | Time to maximum plasma concentration | up to 19 days | 
| Pharmacokinetic evaluation of levodopa following administration of opicapone: area under the curve (AUC 0-tlast) | Area under the plasma concentration versus time curve from 0 hours to time before next levodopa dose | up to 15 days | 
| Pharmacokinetic evaluation of levodopa following administration of opicapone: maximum plasma concentration (cmax) | Maximum plasma concentration | up to 15 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events (safety and tolerability) | Number of participants with reported adverse events after study treatment. | up to 19 days | 
| Pharmacodynamic evaluation of opicapone on S-COMT activity | Maximum inhibition of S-COMT activity. | up to 19 days |