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

Primary Purpose

Parkinson Disease

Status

Completed

Phase

Phase 1

Locations

Portugal

Study Type

Interventional

Intervention

Placebo

BIA 6-512

Madopar® 250

Comtan®

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, 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.

Sites / Locations

Human Pharmacology Unit (UFH) - BIAL - Portela & Cª, SA

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Arm Label

Placebo

BIA 6-512 25 mg

BIA 6-512 50 mg

BIA 6-512 75 mg

BIA 6-512 100 mg

Arm Description

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.

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

Day 4 - Maximum observed plasma drug concentration (Cmax)

BIA 6-512, levodopa, 3-OMD and entacapone pharmacokinetic parameters on day 4

Day 4 - Time of occurrence of Cmax (tmax)

BIA 6-512, levodopa, 3-OMD and entacapone pharmacokinetic parameters on day 4

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)

BIA 6-512, levodopa, 3-OMD and entacapone pharmacokinetic parameters on day 4

Day 4 - AUC from time zero to 8 h post-dose (AUC0-τ)

BIA 6-512, levodopa, 3-OMD and entacapone pharmacokinetic parameters on day 4

Day 4 - Apparent terminal elimination half-life, calculated from ln 2/λz (t1/2)

BIA 6-512, levodopa, 3-OMD and entacapone pharmacokinetic parameters on day 4

Day 4 - Area under the plasma concentration versus time curve from time zero to infinity (AUC0-∞)

BIA 6-512, levodopa, 3-OMD and entacapone pharmacokinetic parameters on day 4

Day 5 - Maximum observed plasma drug concentration (Cmax)

Day 5 - Time of occurrence of Cmax (tmax)

BIA 6-512, levodopa, 3-OMD and entacapone pharmacokinetic parameters on day 5

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)

BIA 6-512, levodopa, 3-OMD and entacapone pharmacokinetic parameters on day 5

Day 5 - AUC from time zero to 8 h post-dose (AUC0-τ)

BIA 6-512, levodopa, 3-OMD and entacapone pharmacokinetic parameters on day 5

Day 5 - Apparent terminal elimination half-life, calculated from ln 2/λz (t1/2)

BIA 6-512, levodopa, 3-OMD and entacapone pharmacokinetic parameters on day 5

Day 5 - Area under the plasma concentration versus time curve from time zero to infinity (AUC0-∞)

BIA 6-512, levodopa, 3-OMD and entacapone pharmacokinetic parameters on day 5

Secondary Outcome Measures

Full Information

NCT ID

NCT03094156

First Posted

March 23, 2017

Last Updated

March 29, 2017

Sponsor

Bial - Portela C S.A.

1. Study Identification

Unique Protocol Identification Number

NCT03094156

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2017

Overall Recruitment Status

Completed

Study Start Date

April 26, 2006 (Actual)

Primary Completion Date

July 11, 2006 (Actual)

Study Completion Date

July 11, 2006 (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

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.

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.

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

Sequential Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

39 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Placebo

Arm Type

Experimental

Arm Description

Arm Title

BIA 6-512 25 mg

Arm Type

Experimental

Arm Description

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.

Arm Title

BIA 6-512 50 mg

Arm Type

Experimental

Arm Description

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.

Arm Title

BIA 6-512 75 mg

Arm Type

Experimental

Arm Description

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.

Arm Title

BIA 6-512 100 mg

Arm Type

Experimental

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

1 capsule of placebo [to be taken orally, with 240 mL of potable water]

Intervention Type

Drug

Intervention Name(s)

BIA 6-512

Other Intervention Name(s)

Trans-resveratrol

Intervention Description

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]

Intervention Type

Drug

Intervention Name(s)

Madopar® 250

Intervention Description

Levodopa/benserazide immediate release tablets 200mg/50mg [to be taken orally, with 240 mL of potable water]

Intervention Type

Drug

Intervention Name(s)

Comtan®

Intervention Description

Entacapone 200 mg tablets [to be taken orally, with 240 mL of potable water]

Primary Outcome Measure Information:

Title

Day 4 - Maximum observed plasma drug concentration (Cmax)

Description

BIA 6-512, levodopa, 3-OMD and entacapone pharmacokinetic parameters on day 4

Time Frame

pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8 and 16 hours post-dose

Title

Day 4 - Time of occurrence of Cmax (tmax)

Description

BIA 6-512, levodopa, 3-OMD and entacapone pharmacokinetic parameters on day 4

Time Frame

pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8 and 16 hours post-dose

Title

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)

Description

BIA 6-512, levodopa, 3-OMD and entacapone pharmacokinetic parameters on day 4

Time Frame

pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8 and 16 hours post-dose

Title

Day 4 - AUC from time zero to 8 h post-dose (AUC0-τ)

Description

BIA 6-512, levodopa, 3-OMD and entacapone pharmacokinetic parameters on day 4

Time Frame

pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8 and 16 hours post-dose

Title

Day 4 - Apparent terminal elimination half-life, calculated from ln 2/λz (t1/2)

Description

BIA 6-512, levodopa, 3-OMD and entacapone pharmacokinetic parameters on day 4

Time Frame

pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8 and 16 hours post-dose

Title

Day 4 - Area under the plasma concentration versus time curve from time zero to infinity (AUC0-∞)

Description

BIA 6-512, levodopa, 3-OMD and entacapone pharmacokinetic parameters on day 4

Time Frame

pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8 and 16 hours post-dose

Title

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

Title

Day 5 - Time of occurrence of Cmax (tmax)

Description

BIA 6-512, levodopa, 3-OMD and entacapone pharmacokinetic parameters on day 5

Time Frame

pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 16 and 24 hours post-dose

Title

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)

Description

BIA 6-512, levodopa, 3-OMD and entacapone pharmacokinetic parameters on day 5

Time Frame

pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 16 and 24 hours post-dose

Title

Day 5 - AUC from time zero to 8 h post-dose (AUC0-τ)

Description

BIA 6-512, levodopa, 3-OMD and entacapone pharmacokinetic parameters on day 5

Time Frame

pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 16 and 24 hours post-dose

Title

Day 5 - Apparent terminal elimination half-life, calculated from ln 2/λz (t1/2)

Description

BIA 6-512, levodopa, 3-OMD and entacapone pharmacokinetic parameters on day 5

Time Frame

pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 16 and 24 hours post-dose

Title

Day 5 - Area under the plasma concentration versus time curve from time zero to infinity (AUC0-∞)

Description

BIA 6-512, levodopa, 3-OMD and entacapone pharmacokinetic parameters on day 5

Time Frame

pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 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, 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.

Facility Information:

Facility Name

Human Pharmacology Unit (UFH) - BIAL - Portela & Cª, SA

City

S. Mamede do Coronado

ZIP/Postal Code

4745-457

Country

Portugal

12. IPD Sharing Statement

Plan to Share IPD

Undecided

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

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