Effect of BIA 6-512 at Steady-state on the Levodopa Pharmacokinetics

March 29, 2017 updated by: Bial - Portela C S.A.

A Double-blind, Randomised, Placebo-controlled, Rising Multiple Dose Study in Healthy Volunteers to Investigate the Effect of BIA 6-512 at Steady-state on the Levodopa Pharmacokinetics When Administered in Combination With a Single-dose of Levodopa/Benserazide 200/50 mg or With a Single-dose of Levodopa/Benserazide 200/50 mg Plus a Single-dose of Entacapone 200 mg

The purpose of the study was to To investigate whether the administration of BIA 6-512 (25 mg, 50 mg, 75 mg and 100 mg) at steady-state affects the pharmacokinetics of levodopa when administered in combination with a single-dose of immediate release levodopa/benserazide 200/50 mg or with a single-dose of immediate release levodopa/benserazide 200/50 mg plus a single-dose of entacapone 200 mg.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Single centre, double-blind, randomised, placebo-controlled, rising multiple-dose study in four sequential groups of healthy male and female subjects. Eligible subjects were admitted to the Human Pharmacology Unit (UFHBIAL - Portela & Cª, SA) on the day prior to receiving the first study medication. Starting in the morning of Day 1 (first dose), subjects received BIA 6-512/Placebo thrice-daily until the morning of Day 5 (last dose). Concomitantly with the morning dose of BIA 6-512/Placebo, on Day 4 a levodopa/benserazide 200/50 mg (Madopar® 250) single-dose was administered. On Day 5, a Madopar® 250 single-dose and a entacapone 200 mg (Comtan®) single-dose were administered concomitantly with the morning dose of BIA 6-512/Placebo. In the morning of Day 4 and Day 5, products were administered in fasting of at least 8 hours and subjects remained fasted until 2 h post-dose. Subjects were resident in the UFH from admission (Day 0) until at least 24 h post last dose (Day 6); then, they were discharged and returned for the follow-up visit.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
39

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

  • Portugal
      • S. Mamede do Coronado, Portugal, 4745-457
        • Human Pharmacology Unit (UFH) - BIAL - Portela & Cª, SA

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 45 years (ADULT)

Accepts Healthy Volunteers

Yes

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, vital signs, complete neurological examination and 12-lead ECG.
  • Subjects who had negative tests for HBsAg, anti-HCVAb and HIV-1 and HIV-2 Ab at screening
  • Subjects who had clinical laboratory test results clinically acceptable at screening and admission.
  • Subjects who had a negative screen for alcohol and drugs of abuse at screening and admission.
  • Subjects who were non-smokers or who smoked ≤ 10 cigarettes or equivalent per day.
  • Subjects who were able and willing to gave 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 urine pregnancy test at screening and admission.

Exclusion Criteria:

  • 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 14 units of alcohol a week.
  • Subjects who had a significant infection or known inflammatory process on screening or admission.
  • Subjects who had acute gastrointestinal symptoms (e.g., nausea, vomiting, diarrhoea, heartburn) at the time of screening or admission.
  • Subjects who had used medicines within 2 weeks of admission that may affect the safety or other study assessments, in the investigator's opinion.
  • Subjects who had previously participated in a clinical trial with BIA 6-512.
  • Subjects who had used any investigational drug or participated in any clinical trial within 6 months prior to screening.
  • Subjects who had participated in more than 2 clinical trials within the 12 months prior to screening.
  • Subjects who had donated or received any blood or blood products within the 3 months prior to screening.
  • Subjects who were vegetarians, vegans 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 effective contraceptive method (double-barrier, intra-uterine device or abstinence) 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: SEQUENTIAL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: Placebo
Subjects were administered with those investigational products at approximately 8-h intervals, starting in the morning (approximately at 8h00) of Day 1 and finishing in the morning of Day 5 (last dose). On Day 4, concomitantly with the Placebo morning dose, one tablet of Madopar® 250 was administered. On Day 5, concomitantly with the Placebo morning dose, one tablet of Madopar® 250 and one tablet of Comtan® were administered.
Drug: Placebo
1 capsule of placebo [to be taken orally, with 240 mL of potable water]
Drug: Madopar® 250
Levodopa/benserazide immediate release tablets 200mg/50mg [to be taken orally, with 240 mL of potable water]
Drug: Comtan®
Entacapone 200 mg tablets [to be taken orally, with 240 mL of potable water]
EXPERIMENTAL: BIA 6-512 25 mg
Subjects were administered with those investigational products at approximately 8-h intervals, starting in the morning (approximately at 8h00) of Day 1 and finishing in the morning of Day 5 (last dose). On Day 4, concomitantly with the BIA 6-512 25 mg morning dose, one tablet of Madopar® 250 was administered. On Day 5, concomitantly with the BIA 6-512 25 mg morning dose, one tablet of Madopar® 250 and one tablet of Comtan® were administered.
Drug: Madopar® 250
Levodopa/benserazide immediate release tablets 200mg/50mg [to be taken orally, with 240 mL of potable water]
Drug: Comtan®
Entacapone 200 mg tablets [to be taken orally, with 240 mL of potable water]
Drug: BIA 6-512
1 capsule of BIA 6-512 25mg or 1 capsule of BIA 6-512 50 mg or 1 capsule of BIA 6-512 75 mg or 1 capsule of BIA 6-512 100 mg [to be taken orally, with 240 mL of potable water]
Other Names:
  • Trans-resveratrol
EXPERIMENTAL: BIA 6-512 50 mg
Subjects were administered with those investigational products at approximately 8-h intervals, starting in the morning (approximately at 8h00) of Day 1 and finishing in the morning of Day 5 (last dose). On Day 4, concomitantly with the BIA 6-512 50 mg morning dose, one tablet of Madopar® 250 was administered. On Day 5, concomitantly with the BIA 6-512 50 mg morning dose, one tablet of Madopar® 250 and one tablet of Comtan® were administered.
Drug: Madopar® 250
Levodopa/benserazide immediate release tablets 200mg/50mg [to be taken orally, with 240 mL of potable water]
Drug: Comtan®
Entacapone 200 mg tablets [to be taken orally, with 240 mL of potable water]
Drug: BIA 6-512
1 capsule of BIA 6-512 25mg or 1 capsule of BIA 6-512 50 mg or 1 capsule of BIA 6-512 75 mg or 1 capsule of BIA 6-512 100 mg [to be taken orally, with 240 mL of potable water]
Other Names:
  • Trans-resveratrol
EXPERIMENTAL: BIA 6-512 75 mg
Subjects were administered with those investigational products at approximately 8-h intervals, starting in the morning (approximately at 8h00) of Day 1 and finishing in the morning of Day 5 (last dose). On Day 4, concomitantly with the BIA 6-512 75 mg morning dose, one tablet of Madopar® 250 was administered. On Day 5, concomitantly with the BIA 6-512 75 mg morning dose, one tablet of Madopar® 250 and one tablet of Comtan® were administered.
Drug: Madopar® 250
Levodopa/benserazide immediate release tablets 200mg/50mg [to be taken orally, with 240 mL of potable water]
Drug: Comtan®
Entacapone 200 mg tablets [to be taken orally, with 240 mL of potable water]
Drug: BIA 6-512
1 capsule of BIA 6-512 25mg or 1 capsule of BIA 6-512 50 mg or 1 capsule of BIA 6-512 75 mg or 1 capsule of BIA 6-512 100 mg [to be taken orally, with 240 mL of potable water]
Other Names:
  • Trans-resveratrol
EXPERIMENTAL: BIA 6-512 100 mg
Subjects were administered with those investigational products at approximately 8-h intervals, starting in the morning (approximately at 8h00) of Day 1 and finishing in the morning of Day 5 (last dose). On Day 4, concomitantly with the BIA 6-512 100 mg morning dose, one tablet of Madopar® 250 was administered. On Day 5, concomitantly with the BIA 6-512 100 mg morning dose, one tablet of Madopar® 250 and one tablet of Comtan® were administered.
Drug: Madopar® 250
Levodopa/benserazide immediate release tablets 200mg/50mg [to be taken orally, with 240 mL of potable water]
Drug: Comtan®
Entacapone 200 mg tablets [to be taken orally, with 240 mL of potable water]
Drug: BIA 6-512
1 capsule of BIA 6-512 25mg or 1 capsule of BIA 6-512 50 mg or 1 capsule of BIA 6-512 75 mg or 1 capsule of BIA 6-512 100 mg [to be taken orally, with 240 mL of potable water]
Other Names:
  • Trans-resveratrol

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Day 4 - Maximum observed plasma drug concentration (Cmax)
Time Frame: pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8 and 16 hours post-dose
BIA 6-512, levodopa, 3-OMD and entacapone pharmacokinetic parameters on day 4
pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8 and 16 hours post-dose
Day 4 - Time of occurrence of Cmax (tmax)
Time Frame: pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8 and 16 hours post-dose
BIA 6-512, levodopa, 3-OMD and entacapone pharmacokinetic parameters on day 4
pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8 and 16 hours post-dose
Day 4 - 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)
Time Frame: pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8 and 16 hours post-dose
BIA 6-512, levodopa, 3-OMD and entacapone pharmacokinetic parameters on day 4
pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8 and 16 hours post-dose
Day 4 - AUC from time zero to 8 h post-dose (AUC0-τ)
Time Frame: pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8 and 16 hours post-dose
BIA 6-512, levodopa, 3-OMD and entacapone pharmacokinetic parameters on day 4
pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8 and 16 hours post-dose
Day 4 - Apparent terminal elimination half-life, calculated from ln 2/λz (t1/2)
Time Frame: pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8 and 16 hours post-dose
BIA 6-512, levodopa, 3-OMD and entacapone pharmacokinetic parameters on day 4
pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8 and 16 hours post-dose
Day 4 - Area under the plasma concentration versus time curve from time zero to infinity (AUC0-∞)
Time Frame: pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8 and 16 hours post-dose
BIA 6-512, levodopa, 3-OMD and entacapone pharmacokinetic parameters on day 4
pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8 and 16 hours post-dose
Day 5 - Maximum observed plasma drug concentration (Cmax)
Time Frame: pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 16 and 24 hours post-dose
pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 16 and 24 hours post-dose
Day 5 - Time of occurrence of Cmax (tmax)
Time Frame: pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 16 and 24 hours post-dose
BIA 6-512, levodopa, 3-OMD and entacapone pharmacokinetic parameters on day 5
pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 16 and 24 hours post-dose
Day 5 - 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)
Time Frame: pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 16 and 24 hours post-dose
BIA 6-512, levodopa, 3-OMD and entacapone pharmacokinetic parameters on day 5
pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 16 and 24 hours post-dose
Day 5 - AUC from time zero to 8 h post-dose (AUC0-τ)
Time Frame: pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 16 and 24 hours post-dose
BIA 6-512, levodopa, 3-OMD and entacapone pharmacokinetic parameters on day 5
pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 16 and 24 hours post-dose
Day 5 - Apparent terminal elimination half-life, calculated from ln 2/λz (t1/2)
Time Frame: pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 16 and 24 hours post-dose
BIA 6-512, levodopa, 3-OMD and entacapone pharmacokinetic parameters on day 5
pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 16 and 24 hours post-dose
Day 5 - Area under the plasma concentration versus time curve from time zero to infinity (AUC0-∞)
Time Frame: pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 16 and 24 hours post-dose
BIA 6-512, levodopa, 3-OMD and entacapone pharmacokinetic parameters on day 5
pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 16 and 24 hours post-dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Bial - Portela C S.A.

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 26, 2006

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 11, 2006

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 11, 2006

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 23, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 28, 2017

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 29, 2017

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 30, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 29, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • BIA-6512-106

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

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