- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03091543
Tolerability, Safety and Pharmacokinetics of Four Single-doses of BIA 6-512 (Trans-resveratrol) and Their Effect on the Levodopa Pharmacokinetics
March 21, 2017 updated by: Bial - Portela C S.A.
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
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.
Study Overview
Status
Completed
Conditions
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.
Study Type
Interventional
Enrollment (Actual)
20
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
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S. Mamede do Coronado, Portugal, 4745-457
- Human Pharmacology Unit (UFH)
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 45 years (Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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.
|
1 capsule of Madopar® HBS 125 (levodopa 100 mg / benserazide 25 mg) in an open label manner, concomitantly with BIA 6-512/Placebo.
2 capsules of placebo
1 capsule of 25 mg plus 1 capsule of placebo
2 capsules of 25 mg
1 capsule of 100 mg plus 1 capsule of placebo
2 capsules of 100 mg
|
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.
|
1 capsule of Madopar® HBS 125 (levodopa 100 mg / benserazide 25 mg) in an open label manner, concomitantly with BIA 6-512/Placebo.
2 capsules of placebo
1 capsule of 25 mg plus 1 capsule of placebo
2 capsules of 25 mg
1 capsule of 100 mg plus 1 capsule of placebo
2 capsules of 100 mg
|
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.
|
1 capsule of Madopar® HBS 125 (levodopa 100 mg / benserazide 25 mg) in an open label manner, concomitantly with BIA 6-512/Placebo.
2 capsules of placebo
1 capsule of 25 mg plus 1 capsule of placebo
2 capsules of 25 mg
1 capsule of 100 mg plus 1 capsule of placebo
2 capsules of 100 mg
|
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.
|
1 capsule of Madopar® HBS 125 (levodopa 100 mg / benserazide 25 mg) in an open label manner, concomitantly with BIA 6-512/Placebo.
2 capsules of placebo
1 capsule of 25 mg plus 1 capsule of placebo
2 capsules of 25 mg
1 capsule of 100 mg plus 1 capsule of placebo
2 capsules of 100 mg
|
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.
|
1 capsule of Madopar® HBS 125 (levodopa 100 mg / benserazide 25 mg) in an open label manner, concomitantly with BIA 6-512/Placebo.
2 capsules of placebo
1 capsule of 25 mg plus 1 capsule of placebo
2 capsules of 25 mg
1 capsule of 100 mg plus 1 capsule of placebo
2 capsules of 100 mg
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
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
|
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.
|
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
|
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.
|
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
|
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
Time Frame: pre-dose, ¼, ½, 1, 1½, 2, 3, 4, 6, 9, 12, 16 and 24 hours post-dose.
|
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
|
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
Time Frame: pre-dose, ¼, ½, 1, 1½, 2, 3, 4, 6, 9, 12, 16 and 24 hours post-dose.
|
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
|
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.
|
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
|
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.
|
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
|
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.
|
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
|
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
Time Frame: pre-dose, ¼, ½, 1, 1½, 2, 3, 4, 6, 9, 12, 16 and 24 hours post-dose.
|
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
|
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
Time Frame: pre-dose, ¼, ½, 1, 1½, 2, 3, 4, 6, 9, 12, 16 and 24 hours post-dose.
|
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
|
pre-dose, ¼, ½, 1, 1½, 2, 3, 4, 6, 9, 12, 16 and 24 hours post-dose.
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
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
|
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.
|
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
|
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.
|
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
|
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
Time Frame: pre-dose, ¼, ½, 1, 1½, 2, 3, 4, 6, 9, 12, 16 and 24 hours post-dose.
|
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
|
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
Time Frame: pre-dose, ¼, ½, 1, 1½, 2, 3, 4, 6, 9, 12, 16 and 24 hours post-dose.
|
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
|
pre-dose, ¼, ½, 1, 1½, 2, 3, 4, 6, 9, 12, 16 and 24 hours post-dose.
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
May 4, 2004
Primary Completion (Actual)
July 23, 2004
Study Completion (Actual)
July 23, 2004
Study Registration Dates
First Submitted
March 21, 2017
First Submitted That Met QC Criteria
March 21, 2017
First Posted (Actual)
March 27, 2017
Study Record Updates
Last Update Posted (Actual)
March 27, 2017
Last Update Submitted That Met QC Criteria
March 21, 2017
Last Verified
March 1, 2017
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Parkinsonian Disorders
- Basal Ganglia Diseases
- Movement Disorders
- Synucleinopathies
- Neurodegenerative Diseases
- Parkinson Disease
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Dopamine Agents
- Benserazide, levodopa drug combination
Other Study ID Numbers
- BIA-6512-101
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Undecided
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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