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

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT03091543
• Date of registration: 21/03/2017
• Prospective Registration: No
• Primary sponsor: Bial - Portela C S.A.
• Public title: Tolerability, Safety and Pharmacokinetics of Four Single-doses of BIA 6-512 (Trans-resveratrol) and Their Effect on the Levodopa Pharmacokinetics
• Scientific title: A Double-blind, Randomised, Crossover, Placebo-controlled Study in Healthy Volunteers to Investigate the Tolerability, Safety and Pharmacokinetics of Four Single-doses of BIA 6-512 (Trans-resveratrol) and Their Effect on the Levodopa Pharmacokinetics When Administered in Combination With a Single-dose of Levodopa/Benserazide 100/25 mg
• Date of first enrolment: May 4, 2004
• Target sample size: 20
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03091543
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Crossover Assignment. Primary purpose: Treatment. Masking: Single (Investigator).
• Phase: Phase 1

Countries of recruitment

Portugal

Key inclusion & exclusion criteria

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.



Age minimum: 18 Years
Age maximum: 45 Years
Gender: All

Health Condition(s) or Problem(s) studied

Parkinson Disease

Intervention(s)

Drug: BIA 6-512 200 mg dose

Drug: BIA 6-512 50 mg dose

Drug: Madopar® HBS 125

Drug: Placebo

Drug: BIA 6-512 100 mg dose

Drug: BIA 6-512 25 mg dose

Primary Outcome(s)

Apparent terminal half-life, calculated from ln 2/?z (t1/2) - Levodopa [Time Frame: pre-dose, ¼, ½, 1, 1½, 2, 3, 4, 6, 9, 12, 16 and 24 hours post-dose.]

Area under the plasma concentration-time curve (AUC) from time zero to the last sampling time at which concentrations were at or above the limit of quantification (AUC0-t), calculated by the linear trapezoidal rule - BIA 6-512 [Time Frame: pre-dose, ¼, ½, 1, 1½, 2, 3, 4, 6, 9, 12, 16 and 24 hours post-dose.]

Maximum observed plasma drug concentration (Cmax) post-dose - Levodopa [Time Frame: pre-dose, ¼, ½, 1, 1½, 2, 3, 4, 6, 9, 12, 16 and 24 hours post-dose.]

Time of occurrence of Cmax (tmax) - Levodopa [Time Frame: pre-dose, ¼, ½, 1, 1½, 2, 3, 4, 6, 9, 12, 16 and 24 hours post-dose.]

Area under the plasma concentration versus time curve from time zero to infinity (AUC0-8), calculated from AUC0-t + (Clast/?z), where Clast is the last quantifiable concentration and ?z the apparent terminal rate constant - BIA 6-512 [Time Frame: pre-dose, ¼, ½, 1, 1½, 2, 3, 4, 6, 9, 12, 16 and 24 hours post-dose.]

Area under the plasma concentration-time curve (AUC) from time zero to the last sampling time at which concentrations were at or above the limit of quantification (AUC0-t), calculated by the linear trapezoidal rule - Levodopa [Time Frame: pre-dose, ¼, ½, 1, 1½, 2, 3, 4, 6, 9, 12, 16 and 24 hours post-dose.]

Apparent terminal half-life, calculated from ln 2/?z (t1/2) - BIA 6-512 [Time Frame: pre-dose, ¼, ½, 1, 1½, 2, 3, 4, 6, 9, 12, 16 and 24 hours post-dose.]

Maximum observed plasma drug concentration (Cmax) post-dose - BIA 6-512 [Time Frame: pre-dose, ¼, ½, 1, 1½, 2, 3, 4, 6, 9, 12, 16 and 24 hours post-dose.]

Time of occurrence of Cmax (tmax) - BIA 6-512 [Time Frame: pre-dose, ¼, ½, 1, 1½, 2, 3, 4, 6, 9, 12, 16 and 24 hours post-dose.]

Area under the plasma concentration versus time curve from time zero to infinity (AUC0-8), calculated from AUC0-t + (Clast/?z), where Clast is the last quantifiable concentration and ?z the apparent terminal rate constant - Levodopa [Time Frame: pre-dose, ¼, ½, 1, 1½, 2, 3, 4, 6, 9, 12, 16 and 24 hours post-dose.]

Secondary Outcome(s)

Maximum observed plasma drug concentration (Cmax) post-dose - 3-OMD [Time Frame: pre-dose, ¼, ½, 1, 1½, 2, 3, 4, 6, 9, 12, 16 and 24 hours post-dose.]

Apparent terminal half-life, calculated from ln 2/?z (t1/2) - 3-OMD [Time Frame: pre-dose, ¼, ½, 1, 1½, 2, 3, 4, 6, 9, 12, 16 and 24 hours post-dose.]

Area under the plasma concentration-time curve (AUC) from time zero to the last sampling time at which concentrations were at or above the limit of quantification (AUC0-t), calculated by the linear trapezoidal rule - 3-OMD [Time Frame: pre-dose, ¼, ½, 1, 1½, 2, 3, 4, 6, 9, 12, 16 and 24 hours post-dose.]

Time of occurrence of Cmax (tmax) - 3-OMD [Time Frame: pre-dose, ¼, ½, 1, 1½, 2, 3, 4, 6, 9, 12, 16 and 24 hours post-dose.]

Area under the plasma concentration versus time curve from time zero to infinity (AUC0-8), calculated from AUC0-t + (Clast/?z), where Clast is the last quantifiable concentration and ?z the apparent terminal rate constant - 3-OMD [Time Frame: pre-dose, ¼, ½, 1, 1½, 2, 3, 4, 6, 9, 12, 16 and 24 hours post-dose.]

Secondary ID(s)

BIA-6512-101

Source(s) of Monetary Support

Please refer to primary and secondary sponsors