Tolerability, Safety and Pharmacokinetics of Four Single-doses of BIA 6-512 (Trans-resveratrol) and Their Effect on the Levodopa Pharmacokinetics

BIAL

Status and phase: Completed; Phase 1

Conditions: Parkinson Disease

Treatments: Drug: BIA 6-512 50 mg dose; Drug: BIA 6-512 100 mg dose; Drug: Placebo; Drug: Madopar® HBS 125; Drug: BIA 6-512 25 mg dose; Drug: BIA 6-512 200 mg dose

Study type: Interventional

Funder types: Industry

Identifiers

NCT03091543

BIA-6512-101

Details and patient eligibility

About

To investigate the effect of four single oral doses of BIA 6-512 (25 mg, 50 mg, 100 mg and 200 mg) on levodopa pharmacokinetics when administered in combination with a single-dose of controlled release levodopa/benserazide 100/25 mg and to assess the tolerability and safety of four single oral doses of BIA 6-512 (25 mg, 50 mg, 100 mg and 200 mg) when administered in combination with a single-dose of controlled release levodopa/benserazide 100/25 mg.

Full description

Single centre, double-blind, randomised, placebo-controlled, crossover study with five single-dose treatment periods, with a washout period between doses of 5 days or more. In each of the five consecutive treatment periods, eligible subjects were admitted to the UFH in the day prior to receiving the study medication. On the morning of the dosing day, subjects received BIA 6-512/Placebo concomitantly with Madopar® HBS 125 in fasting conditions (at least 8 hours) and remained in the UFH until at least 24 h post-dose; then, they were discharged and returned for the next period or the follow-up visit. Blood samples for the assay of plasma BIA 6-512, levodopa and 3-O-methyldopa (3-OMD) were taken at the following times: pre-dose, ¼, ½, 1, 1½, 2, 3, 4, 6, 9, 12, 16 and 24 hours post-dose.

Enrollment: 20 patients

Sex: All

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Male or female subjects aged 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 (including neurological examination), and 12-lead ECG.
• Subjects who had clinical laboratory tests within normal reference values.
• Subjects who were negative for HBsAg, anti-HCVAb and HIV-1 and HIV-2 Ab tests at screening.
• Subjects who had negative for alcohol and drugs of abuse at screening and each admission to each treatment period.
• 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 female) 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.
• (If female) She had a negative pregnancy test at screening and admission to each treatment period.

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 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 and/or first admission.
• Subjects who had acute gastrointestinal symptoms at the time of screening and/or first admission (e.g., nausea, vomiting, diarrhoea, heartburn).
• Subjects who had used prescription or over-the-counter medication within 2 weeks of first admission.
• Subjects who had used any investigational drug and/or participated in any clinical trial within 4 months of their first admission.
• Subjects who had donated and/or received any blood or blood products within the previous 4 months prior to screening.
• Subjects who were vegetarians, vegans and/or have medical dietary restrictions.
• Subjects who cannot 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.
• (If female) She was pregnant or breast-feeding.
• (If female) She was of childbearing potential and she did not use an approved effective contraceptive method or she used oral contraceptives.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Single Blind

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20 participants in 5 patient groups

Sequence A (25 mg - 50 mg - 100 mg - 200 mg - Placebo)

Experimental group

Description:

Concomitantly with the BIA 6-512/Placebo dose, subjects will be administered levodopa/benserazide 100/25 mg. All subjects attended to each 5 treatment periods and received a different dose of BIA 6-512 or placebo in combination with a single-dose of controlled release levodopa/benserazide 100/25 mg in each of these treatment periods. The washout period between periods was 5 days or more.

Treatment:

Drug: Placebo

Drug: BIA 6-512 200 mg dose

Drug: BIA 6-512 50 mg dose

Drug: Madopar® HBS 125

Drug: BIA 6-512 25 mg dose

Drug: BIA 6-512 100 mg dose

Sequence B (Placebo - 25 mg - 50 mg - 100 mg - 200 mg)

Experimental group

Description:

Concomitantly with the BIA 6-512/Placebo dose, subjects will be administered levodopa/benserazide 100/25 mg. All subjects attended to each 5 treatment periods and received a different dose of BIA 6-512 or placebo in combination with a single-dose of controlled release levodopa/benserazide 100/25 mg in each of these treatment periods. The washout period between periods was 5 days or more.

Treatment:

Drug: Placebo

Drug: BIA 6-512 200 mg dose

Drug: BIA 6-512 50 mg dose

Drug: Madopar® HBS 125

Drug: BIA 6-512 25 mg dose

Drug: BIA 6-512 100 mg dose

Sequence C (200 mg - Placebo - 25 mg - 50 mg - 100 mg)

Experimental group

Description:

Concomitantly with the BIA 6-512/Placebo dose, subjects will be administered levodopa/benserazide 100/25 mg. All subjects attended to each 5 treatment periods and received a different dose of BIA 6-512 or placebo in combination with a single-dose of controlled release levodopa/benserazide 100/25 mg in each of these treatment periods. The washout period between periods was 5 days or more.

Treatment:

Drug: Placebo

Drug: BIA 6-512 200 mg dose

Drug: BIA 6-512 50 mg dose

Drug: Madopar® HBS 125

Drug: BIA 6-512 25 mg dose

Drug: BIA 6-512 100 mg dose

Sequence D (100 mg - 200 mg - Placebo - 25 mg - 50 mg)

Experimental group

Description:

Concomitantly with the BIA 6-512/Placebo dose, subjects will be administered levodopa/benserazide 100/25 mg. All subjects attended to each 5 treatment periods and received a different dose of BIA 6-512 or placebo in combination with a single-dose of controlled release levodopa/benserazide 100/25 mg in each of these treatment periods. The washout period between periods was 5 days or more.

Treatment:

Drug: Placebo

Drug: BIA 6-512 200 mg dose

Drug: BIA 6-512 50 mg dose

Drug: Madopar® HBS 125

Drug: BIA 6-512 25 mg dose

Drug: BIA 6-512 100 mg dose

Sequence E (50 mg - 100 mg - 200 mg - Placebo - 25 mg)

Experimental group

Description:

Concomitantly with the BIA 6-512/Placebo dose, subjects will be administered levodopa/benserazide 100/25 mg. All subjects attended to each 5 treatment periods and received a different dose of BIA 6-512 or placebo in combination with a single-dose of controlled release levodopa/benserazide 100/25 mg in each of these treatment periods. The washout period between periods was 5 days or more.

Treatment:

Drug: Placebo

Drug: BIA 6-512 200 mg dose

Drug: BIA 6-512 50 mg dose

Drug: Madopar® HBS 125

Drug: BIA 6-512 25 mg dose

Drug: BIA 6-512 100 mg dose