Pharmacokinetic-pharmacodynamic Interaction Between Three Different Single Doses of BIA 9-1067 and a Single-dose of Controlled-release 100/25 mg Levodopa/Benserazide

Study Overview
=================
Brief Summary
-----------------
To investigate the effect of three single oral doses of BIA 9-1067 (25 mg, 50 mg and 100 mg) on the levodopa pharmacokinetics when administered in combination with a single-dose of controlled-release levodopa 100 mg/benserazide 25 mg (Madopar HBS).

Detailed Description
-----------------
Single centre, double-blind, randomized, placebo-controlled, crossover study with four consecutive single-dose treatment periods. The washout period between doses was to be at least10 days. On each treatment period (25, 50 and 100 mg BIA 9-1067 or placebo), after completion of pre-dose assessments, BIA 9-1067-Placebo was to be administered concomitantly with the dose of Madopar HBS; post-dose assessments were to be completed and subjects were to be discharged 72 h post-dose.

Official Title
-----------------
Pharmacokinetic-pharmacodynamic Interaction Between Three Different Single Doses of BIA 9-1067 and a Single-dose of Controlled-release 100/25 mg Levodopa/Benserazide: a Double-blind, Randomized, Four-way Crossover, Placebo-controlled Study in Healthy Male Subjects

Conditions
-----------------
Parkinson's Disease (PD)

Intervention / Treatment
-----------------
* Drug: BIA 9-1067
* Drug: Placebo
* Drug: Madopar® HBS


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male subjects between 18 and 45 years, inclusive. Subjects of body mass index (BMI) between 19 and 30 kg/m2, inclusive. Subjects who were healthy as determined by pre-study medical history, physical examination, vital signs, complete neurological examination and 12-lead ECG. Subjects who had clinical laboratory test results that were clinically acceptable at screening and admission to first treatment period. Subjects who had negative tests for hepatitis B surface antigen (HBsAg), anti-hepatitis C antibodies (HCV Ab), and Human immunodeficiency viruses -1 and -2 antibodies (HIV-1 and HIV-2 Ab) at screening. Subjects who had/were negative for drugs of abuse at screening and admission to each treatment period. Subjects who were non-smokers or who smoked ≤10 cigarettes or equivalent per day. Subjects who were able and willing to give written informed consent. Exclusion Criteria: Subjects who did not conform to the above inclusion criteria, or Subjects who had a clinically relevant history or presence of respiratory, gastrointestinal, renal, hepatic, haematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, endocrine, connective tissue diseases or disorders. Subjects who had a clinically relevant surgical history. Subjects who had a clinically relevant family history. Subjects who had a history of relevant atopy. Subjects who had a history of relevant drug hypersensitivity. Subjects who had a history of glaucoma. Subjects who had a history of alcoholism or drug abuse. Subjects who consumed more than 21 units of alcohol a week. Subjects who had a significant infection or known inflammatory process on screening or first admission. Subjects who had acute gastrointestinal symptoms at the time of screening or first admission (e.g., nausea, vomiting, diarrhoea, heartburn). Subjects who used medicines within 2 weeks of first admission that, in the opinion of the investigator, may affect the safety or other study assessments. Subjects who used any investigational drug or participated in any clinical trial within 2 months of their first admission. Subjects who donated or received any blood or blood products within the previous 2 months prior to screening. Subjects who were vegetarians, vegans or have medical dietary restrictions. Subjects who could not communicate reliably with the investigator. Subjects who were unlikely to co-operate with the requirements of the study. Subjects who were unwilling or unable to give written informed consent. Subjects who were BIAL - Portela & Cª, SA employees.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>Period 1: BIA 9-1067 25 mg Period 2: BIA 9-1067 50 mg Period 3: BIA 9-1067 100 mg Period 4: Placebo BIA 9-1067/Placebo was to be administered concomitantly with the dose of Madopar® HBS (Single-dose of controlled-release levodopa/benserazide 100/25 mg: 1 capsule of Madopar® HBS.) | Drug: BIA 9-1067<br>* OPC, Opicapone<br>* Other names: OPC, Opicapone;Drug: Placebo<br>* PLC, Placebo<br>* Other names: PLC, Placebo;Drug: Madopar® HBS<br>* controlled-release levodopa 100 mg/benserazide 25 mg<br>|
| Experimental: Group 2<br>Period 1: BIA 9-1067 50 mg Period 2: BIA 9-1067 100 mg Period 3: Placebo Period 4: BIA 9-1067 25 mg BIA 9-1067/Placebo was to be administered concomitantly with the dose of Madopar® HBS (Single-dose of controlled-release levodopa/benserazide 100/25 mg: 1 capsule of Madopar® HBS.) | Drug: BIA 9-1067<br>* OPC, Opicapone<br>* Other names: OPC, Opicapone;Drug: Placebo<br>* PLC, Placebo<br>* Other names: PLC, Placebo;Drug: Madopar® HBS<br>* controlled-release levodopa 100 mg/benserazide 25 mg<br>|
| Experimental: Group 3<br>Period 1: BIA 9-1067 100 mg Period 2: Placebo Period 3: BIA 9-1067 25 mg Period 4: BIA 9-1067 50 mg BIA 9-1067/Placebo was to be administered concomitantly with the dose of Madopar® HBS (Single-dose of controlled-release levodopa/benserazide 100/25 mg: 1 capsule of Madopar® HBS.) | Drug: BIA 9-1067<br>* OPC, Opicapone<br>* Other names: OPC, Opicapone;Drug: Placebo<br>* PLC, Placebo<br>* Other names: PLC, Placebo;Drug: Madopar® HBS<br>* controlled-release levodopa 100 mg/benserazide 25 mg<br>|
| Experimental: Group 4<br>Period 1: Placebo Period 2: BIA 9-1067 25 mg Period 3: BIA 9-1067 50 mg Period 4: BIA 9-1067 100 mg BIA 9-1067/Placebo was to be administered concomitantly with the dose of Madopar® HBS (Single-dose of controlled-release levodopa/benserazide 100/25 mg: 1 capsule of Madopar® HBS.) | Drug: BIA 9-1067<br>* OPC, Opicapone<br>* Other names: OPC, Opicapone;Drug: Placebo<br>* PLC, Placebo<br>* Other names: PLC, Placebo;Drug: Madopar® HBS<br>* controlled-release levodopa 100 mg/benserazide 25 mg<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax - Maximum Observed Plasma Concentration of Levodopa | Primary pharmacokinetic parameter: Levodopa maximum observed plasma concentration (Cmax) (ng/mL) | pre-dose, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 h post-dose. | 
| AUC0-t - Area Under the Plasma Concentration-time Curve | Primary pharmacokinetic parameter: Area under the plasma concentration-time curve for levodopa | pre-dose, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 h post-dose. | 
| AUC0-∞ - AUC From Time Zero to Infinity | Primary pharmacokinetic parameter: Area under the plasma concentration-time curve from time zero to infinity for levodopa | pre-dose, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 h post-dose. | 
| Tmax - Time to Cmax | Primary pharmacokinetic parameter: tmax - time to Cmax | pre-dose, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 h post-dose. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Parkinson's disease (PD), Opicapone, BIA 9-1067