Pharmacokinetic-Pharmacodynamic Interaction Between Four Different Single Doses of BIA 3-202 and a Single Dose of Levodopa/Benserazide (100/25 mg)

BIAL

Status and phase: Completed; Phase 1

Conditions: Parkinson's Disease

Treatments: Drug: BIA 3-202; Drug: Madopar® 125; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT02763852

BIA-3202-104

Details and patient eligibility

About

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.

Full 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.

Enrollment: 18 patients

Sex: All

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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18 participants in 5 patient groups

BIA 3-202 50 mg

Experimental group

Description:

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.

Treatment:

Drug: Madopar® 125

Drug: BIA 3-202

BIA 3-202 100 mg

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Drug: Madopar® 125

Drug: BIA 3-202

BIA 3-202 200 mg

Experimental group

Description:

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

Treatment:

Drug: Placebo

Drug: Madopar® 125

Drug: BIA 3-202

BIA 3-202 300 mg

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Drug: Madopar® 125

Drug: BIA 3-202

BIA 3-202 400 mg

Experimental group

Description:

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

Treatment:

Drug: Placebo

Drug: Madopar® 125

Drug: BIA 3-202