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

Primary Purpose

Parkinson Disease

Status

Completed

Phase

Phase 1

Locations

Portugal

Study Type

Interventional

Intervention

Madopar® HBS 125

Placebo

BIA 6-512 25 mg dose

BIA 6-512 50 mg dose

BIA 6-512 100 mg dose

BIA 6-512 200 mg dose

About this trial

This is an interventional treatment trial for Parkinson Disease

Eligibility Criteria

18 Years - 45 Years (Adult)All SexesAccepts 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.

Sites / Locations

Human Pharmacology Unit (UFH)

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Arm Label

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

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

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

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

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

Arm 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.

Outcomes

Primary Outcome Measures

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 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

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

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

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

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 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

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

Secondary Outcome Measures

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 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

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

Full Information

NCT ID

NCT03091543

First Posted

March 21, 2017

Last Updated

March 21, 2017

Sponsor

Bial - Portela C S.A.

1. Study Identification

Unique Protocol Identification Number

NCT03091543

Brief Title

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

Official 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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2017

Overall Recruitment Status

Completed

Study Start Date

May 4, 2004 (Actual)

Primary Completion Date

July 23, 2004 (Actual)

Study Completion Date

July 23, 2004 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Bial - Portela C S.A.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Parkinson Disease

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Crossover Assignment

Masking

Investigator

Allocation

Randomized

Enrollment

20 (Actual)

8. Arms, Groups, and Interventions

Arm Title

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

Arm Type

Experimental

Arm Description

Arm Title

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

Arm Type

Experimental

Arm Description

Arm Title

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

Arm Type

Experimental

Arm Description

Arm Title

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

Arm Type

Experimental

Arm Description

Arm Title

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

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Madopar® HBS 125

Intervention Description

1 capsule of Madopar® HBS 125 (levodopa 100 mg / benserazide 25 mg) in an open label manner, concomitantly with BIA 6-512/Placebo.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

2 capsules of placebo

Intervention Type

Drug

Intervention Name(s)

BIA 6-512 25 mg dose

Intervention Description

1 capsule of 25 mg plus 1 capsule of placebo

Intervention Type

Drug

Intervention Name(s)

BIA 6-512 50 mg dose

Intervention Description

2 capsules of 25 mg

Intervention Type

Drug

Intervention Name(s)

BIA 6-512 100 mg dose

Intervention Description

1 capsule of 100 mg plus 1 capsule of placebo

Intervention Type

Drug

Intervention Name(s)

BIA 6-512 200 mg dose

Intervention Description

2 capsules of 100 mg

Primary Outcome Measure Information:

Title

Maximum observed plasma drug concentration (Cmax) post-dose - Levodopa

Description

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.

Title

Time of occurrence of Cmax (tmax) - Levodopa

Description

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.

Title

Description

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.

Title

Description

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.

Title

Apparent terminal half-life, calculated from ln 2/λz (t1/2) - Levodopa

Description

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.

Title

Maximum observed plasma drug concentration (Cmax) post-dose - BIA 6-512

Description

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.

Title

Time of occurrence of Cmax (tmax) - BIA 6-512

Description

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.

Title

Description

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.

Title

Description

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.

Title

Apparent terminal half-life, calculated from ln 2/λz (t1/2) - BIA 6-512

Description

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 Outcome Measure Information:

Title

Maximum observed plasma drug concentration (Cmax) post-dose - 3-OMD

Description

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.

Title

Time of occurrence of Cmax (tmax) - 3-OMD

Description

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.

Title

Description

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.

Title

Description

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.

Title

Apparent terminal half-life, calculated from ln 2/λz (t1/2) - 3-OMD

Description

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.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

45 Years

Accepts Healthy Volunteers

Eligibility 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.

Facility Information:

Facility Name

Human Pharmacology Unit (UFH)

City

S. Mamede do Coronado

ZIP/Postal Code

4745-457

Country

Portugal

12. IPD Sharing Statement

Plan to Share IPD

Undecided

Learn more about this trial

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

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