Pharmacokinetic-Pharmacodynamic Interaction Between Four Different Single Doses of BIA 3-202 and a Single Dose of Levodopa/Benserazide (100/25 mg)
Phase 1
Completed
- Conditions
- Parkinson's Disease
- Interventions
- Registration Number
- NCT02763852
- Lead Sponsor
- Bial - Portela C S.A.
- Brief Summary
The purpose of this study is to investigate the tolerability, pharmacokinetic profile of BIA 3-202 and its metabolites, and the pharmacokinetic and pharmacodynamic interaction between 4 different single doses of BIA 3-202 (50 mg, 100 mg, 200 mg and 400 mg) and a single dose of standard levodopa 100 mg/benserazide 25 mg (Madopar® 125) in adult male and female healthy volunteers.
- Detailed Description
This was a single centre, double-blind, randomised, placebo-controlled, single-graded-dose, crossover study with five single-dose treatment periods. The washout period between doses was 15±2 days. For each of the five treatment periods, volunteers were to be admitted at the UFH on the day before the treatment day. On each treatment period, the pre-dose assessment were to be completed, BIA 3-202/Placebo was to be administered concomitantly with the dose of Madopar® 125 and post-dose assessments were to be completed. Subjects were discharged 30 h post-dose. Subjects should attend five treatment periods and were to receive a different dose of BIA 3-202 or placebo during each of these treatment periods.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 18
Inclusion Criteria
- Male and female subjects aged between 18 and 45 years, inclusive.
- Subjects of body mass index (BMI) between 19 and 28 kg/m2, inclusive.
- Subjects who were healthy as determined by pre study medical history, physical examination, and 12- lead ECG.
- Subjects who had clinical laboratory tests acceptable to the investigator.
- Subjects who were negative for HBsAg, anti-HCV Ab and HIV-1 and HIV-2 Ab tests at screening.
- Subjects who were negative for drugs of abuse at screening and admission.
- Subjects who were non-smokers or who smoked less than 10 cigarettes or equivalent per day.
- Subjects who were able and willing to give written informed consent.
- (If a woman) She was not of childbearing potential by reason of surgery or, if of childbearing potential, she used one of the following methods of contraception: double barrier, intrauterine device or abstinence.
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, 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 alcoholism or drug abuse.
- Subjects who consumed more than 28 units of alcohol a week.
- Subjects who had a significant infection or known inflammatory process on screening and/or admission.
- Subjects who had acute gastrointestinal symptoms at the time of screening and/or admission (e.g., nausea, vomiting, diarrhoea, heartburn).
- Subjects who had an acute infection such as influenza at the time of screening and/or admission.
- Subjects who had used prescription drugs within 4 weeks of first dosing.
- Subjects who had used oral contraceptives or over the counter medication excluding oral routine vitamins but including mega dose vitamin therapy within one week of first dosing.
- Subjects who had used any investigational drug and/or participated in any clinical trial within 3 months of their first admission to the study.
- Subjects who had previously received BIA 3-202.
- Subjects who had donated and/or received any blood or blood products within the previous 3 months prior to screening.
- Subjects who were vegetarians, vegans and/or had 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.
- (If woman) She was pregnant or breast-feeding.
- (If woman) She was at childbearing potential and she did not use an approved effective contraceptive method or she used oral contraceptives.
- Subjects who were unwilling or unable to give written informed consent.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description BIA 3-202 50 mg BIA 3-202 BIA 3-202 single-dose plus 1 tablet of Madopar 125. BIA 3-202 50 mg: 5 tablets of 10 mg. The investigational products were administered orally, following an overnight fast of at least 7 hours, with approximately 200 mL of potable water. BIA 3-202 50 mg Madopar® 125 BIA 3-202 single-dose plus 1 tablet of Madopar 125. BIA 3-202 50 mg: 5 tablets of 10 mg. The investigational products were administered orally, following an overnight fast of at least 7 hours, with approximately 200 mL of potable water. BIA 3-202 100 mg Placebo BIA 3-202/Placebo single-dose plus 1 tablet of Madopar 125. BIA 3-202 100 mg: 1 tablet of 100 mg + 4 placebo tablets. The investigational products were administered orally, following an overnight fast of at least 7 hours, with approximately 200 mL of potable water. BIA 3-202 100 mg Madopar® 125 BIA 3-202/Placebo single-dose plus 1 tablet of Madopar 125. BIA 3-202 100 mg: 1 tablet of 100 mg + 4 placebo tablets. The investigational products were administered orally, following an overnight fast of at least 7 hours, with approximately 200 mL of potable water. BIA 3-202 200 mg Placebo BIA 3-202/Placebo single-dose plus 1 tablet of Madopar 125. BIA 3-202 200 mg: 2 tablet of 100 mg + 3 placebo tablets. The investigational products were administered orally, following an overnight fast of at least 7 hours, with approximately 200 mL of potable water BIA 3-202 200 mg Madopar® 125 BIA 3-202/Placebo single-dose plus 1 tablet of Madopar 125. BIA 3-202 200 mg: 2 tablet of 100 mg + 3 placebo tablets. The investigational products were administered orally, following an overnight fast of at least 7 hours, with approximately 200 mL of potable water BIA 3-202 300 mg Placebo BIA 3-202/Placebo single-dose plus 1 tablet of Madopar 125. BIA 3-202 300 mg: 3 tablet of 100 mg + 2 placebo tablets. The investigational products were administered orally, following an overnight fast of at least 7 hours, with approximately 200 mL of potable water. BIA 3-202 300 mg Madopar® 125 BIA 3-202/Placebo single-dose plus 1 tablet of Madopar 125. BIA 3-202 300 mg: 3 tablet of 100 mg + 2 placebo tablets. The investigational products were administered orally, following an overnight fast of at least 7 hours, with approximately 200 mL of potable water. BIA 3-202 400 mg Placebo BIA 3-202/Placebo single-dose plus 1 tablet of Madopar 125. BIA 3-202 400 mg: 4 tablet of 100 mg + 1 placebo tablets. The investigational products were administered orally, following an overnight fast of at least 7 hours, with approximately 200 mL of potable water BIA 3-202 400 mg Madopar® 125 BIA 3-202/Placebo single-dose plus 1 tablet of Madopar 125. BIA 3-202 400 mg: 4 tablet of 100 mg + 1 placebo tablets. The investigational products were administered orally, following an overnight fast of at least 7 hours, with approximately 200 mL of potable water BIA 3-202 300 mg BIA 3-202 BIA 3-202/Placebo single-dose plus 1 tablet of Madopar 125. BIA 3-202 300 mg: 3 tablet of 100 mg + 2 placebo tablets. The investigational products were administered orally, following an overnight fast of at least 7 hours, with approximately 200 mL of potable water. BIA 3-202 400 mg BIA 3-202 BIA 3-202/Placebo single-dose plus 1 tablet of Madopar 125. BIA 3-202 400 mg: 4 tablet of 100 mg + 1 placebo tablets. The investigational products were administered orally, following an overnight fast of at least 7 hours, with approximately 200 mL of potable water BIA 3-202 100 mg BIA 3-202 BIA 3-202/Placebo single-dose plus 1 tablet of Madopar 125. BIA 3-202 100 mg: 1 tablet of 100 mg + 4 placebo tablets. The investigational products were administered orally, following an overnight fast of at least 7 hours, with approximately 200 mL of potable water. BIA 3-202 200 mg BIA 3-202 BIA 3-202/Placebo single-dose plus 1 tablet of Madopar 125. BIA 3-202 200 mg: 2 tablet of 100 mg + 3 placebo tablets. The investigational products were administered orally, following an overnight fast of at least 7 hours, with approximately 200 mL of potable water
- Primary Outcome Measures
Name Time Method Maximum observed plasma concentration (Cmax) pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 18 and 24 h post-dose Apparent terminal elimination half-life (t1/2) pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 18 and 24 h post-dose Area under the plasma concentration time curve extrapolated to infinity (AUC0-∞) pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 18 and 24 h post-dose
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
Human Pharmacology Unit - BIAL - Portela & Ca, S.A.
🇵🇹S. Mamede do Coronado, Portugal