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

NCT03091543 | Completed Phase 1

• 1 other identifier: BIA-6512-101
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Parkinson Disease

Outcome Measures

Primary Outcomes (10)

• 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

  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

  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

  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

  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

  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

  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

  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

  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

  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

  pre-dose, ¼, ½, 1, 1½, 2, 3, 4, 6, 9, 12, 16 and 24 hours post-dose.

Secondary Outcomes (5)

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

  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

  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

  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

  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

  pre-dose, ¼, ½, 1, 1½, 2, 3, 4, 6, 9, 12, 16 and 24 hours post-dose.

Study Arms (5)

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

EXPERIMENTAL

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

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

EXPERIMENTAL

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

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

EXPERIMENTAL

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

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

EXPERIMENTAL

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

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

EXPERIMENTAL

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

Madopar® HBS 125 DRUG

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

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)

Placebo DRUG

2 capsules of placebo

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)

BIA 6-512 25 mg dose DRUG

1 capsule of 25 mg plus 1 capsule of placebo

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)

BIA 6-512 50 mg dose DRUG

2 capsules of 25 mg

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)

BIA 6-512 100 mg dose DRUG

1 capsule of 100 mg plus 1 capsule of placebo

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)

BIA 6-512 200 mg dose DRUG

2 capsules of 100 mg

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)

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Bial - Portela C S.A.: lead

Study Sites (1)

Human Pharmacology Unit (UFH)

S. Mamede Do Coronado, 4745-457, Portugal

Location

MeSH Terms

Conditions

Parkinson Disease

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 21, 2017
• First Posted: March 27, 2017
• Study Start: May 4, 2004
• Primary Completion: July 23, 2004
• Study Completion: July 23, 2004
• Last Updated: March 27, 2017

Record last verified: 2017-03

Locations

PT (1)