CompletedNCT03091543Updated Mar 27, 2017

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

A Phase 1 interventional study of Madopar® HBS 125 and Placebo in Parkinson Disease, sponsored by Bial - Portela C S.A.. Completed at 1 site in Portugal. Open to participants aged 18 Years to 45 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2017-03-27.

Sponsored by Bial - Portela C S.A. · Phase 1, Interventional, and Treatment

From the registry’s dates

Registered 12 years 10 months after the study started (first participant enrolled May 2004, registered Mar 2017).

Phase: Phase 1
Study type: Interventional
Enrollment: 20
Allocation: Randomized
Ages: 18 Years to 45 Years
Sex: All

Study summary

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.

Read the detailed 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.

Conditions studied

Parkinson Disease

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Parkinson Disease 4,487

In context

Parkinson Disease

4,487 studies on the registry are indexed under Parkinson Disease; 1,082 are open to participants now.

This study's enrollment of 20 is below the median of 40 across 3,294 interventional studies indexed under Parkinson Disease.

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Lead sponsor

Bial - Portela C S.A. is the lead sponsor of 133 studies on the registry; 1 is open to participants now.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 45 Years
Sexes eligible: All
Accepts healthy volunteers: Yes

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

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.

Study design

Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover assignment
Masking: Single (Investigator)
Enrollment: 20 participants (actual)

Study arms

Experimental
Sequence A (25 mg - 50 mg - 100 mg - 200 mg - Placebo)
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.
Drug: Madopar® HBS 125 · Drug: Placebo · Drug: BIA 6-512 25 mg dose · Drug: BIA 6-512 50 mg dose · Drug: BIA 6-512 100 mg dose · Drug: BIA 6-512 200 mg dose
Experimental
Sequence B (Placebo - 25 mg - 50 mg - 100 mg - 200 mg)
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.
Drug: Madopar® HBS 125 · Drug: Placebo · Drug: BIA 6-512 25 mg dose · Drug: BIA 6-512 50 mg dose · Drug: BIA 6-512 100 mg dose · Drug: BIA 6-512 200 mg dose
Experimental
Sequence C (200 mg - Placebo - 25 mg - 50 mg - 100 mg)
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.
Drug: Madopar® HBS 125 · Drug: Placebo · Drug: BIA 6-512 25 mg dose · Drug: BIA 6-512 50 mg dose · Drug: BIA 6-512 100 mg dose · Drug: BIA 6-512 200 mg dose
Experimental
Sequence D (100 mg - 200 mg - Placebo - 25 mg - 50 mg)
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.
Drug: Madopar® HBS 125 · Drug: Placebo · Drug: BIA 6-512 25 mg dose · Drug: BIA 6-512 50 mg dose · Drug: BIA 6-512 100 mg dose · Drug: BIA 6-512 200 mg dose
Experimental
Sequence E (50 mg - 100 mg - 200 mg - Placebo - 25 mg)
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.
Drug: Madopar® HBS 125 · Drug: Placebo · Drug: BIA 6-512 25 mg dose · Drug: BIA 6-512 50 mg dose · Drug: BIA 6-512 100 mg dose · Drug: BIA 6-512 200 mg dose

Interventions

DrugMadopar® HBS 125
1 capsule of Madopar® HBS 125 (levodopa 100 mg / benserazide 25 mg) in an open label manner, concomitantly with BIA 6-512/Placebo.
DrugPlacebo
2 capsules of placebo
DrugBIA 6-512 25 mg dose
1 capsule of 25 mg plus 1 capsule of placebo
DrugBIA 6-512 50 mg dose
2 capsules of 25 mg
DrugBIA 6-512 100 mg dose
1 capsule of 100 mg plus 1 capsule of placebo
DrugBIA 6-512 200 mg dose
2 capsules of 100 mg

What researchers measure

Primary outcomes

Maximum observed plasma drug concentration (Cmax) post-dose - Levodopa
Pharmacokinetic parameters of Levodopa following oral administration of single-doses of Madopar® HBS 125 concomitantly with placebo or BIA 6-512 25 mg, 50 mg, 100 mg and 200 mg
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
Pharmacokinetic parameters of Levodopa following oral administration of single-doses of Madopar® HBS 125 concomitantly with placebo or BIA 6-512 25 mg, 50 mg, 100 mg and 200 mg
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
Pharmacokinetic parameters of Levodopa following oral administration of single-doses of Madopar® HBS 125 concomitantly with placebo or BIA 6-512 25 mg, 50 mg, 100 mg and 200 mg
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-∞), calculated from AUC0-t + (Clast/λz), where Clast is the last quantifiable concentration and λz the apparent terminal rate constant - Levodopa
Pharmacokinetic parameters of Levodopa following oral administration of single-doses of Madopar® HBS 125 concomitantly with placebo or BIA 6-512 25 mg, 50 mg, 100 mg and 200 mg
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/λz (t1/2) - Levodopa
Pharmacokinetic parameters of Levodopa following oral administration of single-doses of Madopar® HBS 125 concomitantly with placebo or BIA 6-512 25 mg, 50 mg, 100 mg and 200 mg
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
Pharmacokinetic parameters of BIA 6-512 following oral administration of single-doses of Madopar® HBS 125 concomitantly with placebo or BIA 6-512 25 mg, 50 mg, 100 mg and 200 mg
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
Pharmacokinetic parameters of BIA 6-512 following oral administration of single-doses of Madopar® HBS 125 concomitantly with placebo or BIA 6-512 25 mg, 50 mg, 100 mg and 200 mg
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
Pharmacokinetic parameters of BIA 6-512 following oral administration of single-doses of Madopar® HBS 125 concomitantly with placebo or BIA 6-512 25 mg, 50 mg, 100 mg and 200 mg
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-∞), calculated from AUC0-t + (Clast/λz), where Clast is the last quantifiable concentration and λz the apparent terminal rate constant - BIA 6-512
Pharmacokinetic parameters of BIA 6-512 following oral administration of single-doses of Madopar® HBS 125 concomitantly with placebo or BIA 6-512 25 mg, 50 mg, 100 mg and 200 mg
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/λz (t1/2) - BIA 6-512
Pharmacokinetic parameters of BIA 6-512 following oral administration of single-doses of Madopar® HBS 125 concomitantly with placebo or BIA 6-512 25 mg, 50 mg, 100 mg and 200 mg
Time frame: pre-dose, ¼, ½, 1, 1½, 2, 3, 4, 6, 9, 12, 16 and 24 hours post-dose.

Secondary outcomes

Maximum observed plasma drug concentration (Cmax) post-dose - 3-OMD
Pharmacokinetic parameters of 3-O-methyldopa (3-OMD) following oral administration of single-doses of Madopar® HBS 125 concomitantly with placebo or BIA 6-512 25 mg, 50 mg, 100 mg and 200 mg
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
Pharmacokinetic parameters of 3-O-methyldopa (3-OMD) following oral administration of single-doses of Madopar® HBS 125 concomitantly with placebo or BIA 6-512 25 mg, 50 mg, 100 mg and 200 mg
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
Pharmacokinetic parameters of 3-O-methyldopa (3-OMD) following oral administration of single-doses of Madopar® HBS 125 concomitantly with placebo or BIA 6-512 25 mg, 50 mg, 100 mg and 200 mg
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-∞), calculated from AUC0-t + (Clast/λz), where Clast is the last quantifiable concentration and λz the apparent terminal rate constant - 3-OMD
Pharmacokinetic parameters of 3-O-methyldopa (3-OMD) following oral administration of single-doses of Madopar® HBS 125 concomitantly with placebo or BIA 6-512 25 mg, 50 mg, 100 mg and 200 mg
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/λz (t1/2) - 3-OMD
Pharmacokinetic parameters of 3-O-methyldopa (3-OMD) following oral administration of single-doses of Madopar® HBS 125 concomitantly with placebo or BIA 6-512 25 mg, 50 mg, 100 mg and 200 mg
Time frame: pre-dose, ¼, ½, 1, 1½, 2, 3, 4, 6, 9, 12, 16 and 24 hours post-dose.

Study locations

1 site

Human Pharmacology Unit (UFH)
S. Mamede do Coronado, 4745-457, Portugal

References and documents

Individual participant data

Plan to share: Undecided

No publications or documents are linked to this record.

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Mar 27, 2017, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT03091543
Lead sponsor: Bial - Portela C S.A.
Responsible party: Sponsor
First posted: Mar 27, 2017
Start date: May 4, 2004
Primary completion: Jul 23, 2004
Completion: Jul 23, 2004
Last update: Mar 27, 2017

Oversight

Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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