Tolerability and Steady-state Pharmacokinetics of BIA 6-512

NCT03093389 | Completed Phase 1

• 1 other identifier: BIA-6512-103
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

To investigate the tolerability and safety of four multiple-dose regimens of BIA 6-512 (25 mg, 50 mg, 100 mg, and 150 mg 6 times daily) in healthy volunteers and to characterise the steady-state pharmacokinetic profiles of BIA 6-512 (25 mg, 50 mg, 100 mg, and 150 mg 6 times daily) in healthy volunteers.

Conditions

Parkinson Disease

Outcome Measures

Primary Outcomes (12)

• Cmax - the maximum plasma concentration - first dose (dose 1)

  BIA 6-512 pharmacokinetic parameters following the first dose (Dose 1)

  Dose 1: pre-dose and ¼, ½, ¾, 1, 1½, 2, and 3 hours post-dose

• tmax - the time of occurrence of Cmax - first dose (dose 1)

  BIA 6-512 pharmacokinetic parameters following the first dose (Dose 1)

  Dose 1: pre-dose and ¼, ½, ¾, 1, 1½, 2, and 3 hours post-dose

• AUC0-t - the area under the plasma concentration-time curve from time zero to the last sampling time at which concentrations are at or above the limit of quantification, calculated by the linear trapezoidal rule - first dose (dose 1)

  BIA 6-512 pharmacokinetic parameters following the first dose (Dose 1)

  Dose 1: pre-dose and ¼, ½, ¾, 1, 1½, 2, and 3 hours post-dose

• AUC0-τ - the area under the plasma concentration versus time curve over the dosing interval (4 h), calculated by the linear trapezoidal rule - first dose (dose 1)

  BIA 6-512 pharmacokinetic parameters following the first dose (Dose 1)

  Dose 1: pre-dose and ¼, ½, ¾, 1, 1½, 2, and 3 hours post-dose

• AUC0-¥ - the area under the plasma concentration versus time curve from time zero to infinity, calculated from AUC0-t + (Clast/lz), where Clast is the last quantifiable concentration and lz the apparent terminal rate constant - first dose (dose 1)

  BIA 6-512 pharmacokinetic parameters following the first dose (Dose 1)

  Dose 1: pre-dose and ¼, ½, ¾, 1, 1½, 2, and 3 hours post-dose

• t½ - the apparent elimination half-life, calculated from ln 2/lz - first dose (dose 1)

  BIA 6-512 pharmacokinetic parameters following the first dose (Dose 1)

  Dose 1: pre-dose and ¼, ½, ¾, 1, 1½, 2, and 3 hours post-dose

• Cmax - the maximum plasma concentration - last dose (dose 13)

  BIA 6-512 pharmacokinetic parameters following the last dose (Dose 13)

  Dose 13: pre-dose and ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose

• tmax - the time of occurrence of Cmax - last dose (dose 13)

  BIA 6-512 pharmacokinetic parameters following the last dose (Dose 13)

  Dose 13: pre-dose and ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose

• AUC0-t - the area under the plasma concentration-time curve from time zero to the last sampling time at which concentrations are at or above the limit of quantification, calculated by the linear trapezoidal rule - last dose (dose 13)

  BIA 6-512 pharmacokinetic parameters following the last dose (Dose 13)

  Dose 13: pre-dose and ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose

• AUC0-τ - the area under the plasma concentration versus time curve over the dosing interval (4 h), calculated by the linear trapezoidal rule - last dose (dose 13)

  BIA 6-512 pharmacokinetic parameters following the last dose (Dose 13)

  Dose 13: pre-dose and ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose

• AUC0-¥ - the area under the plasma concentration versus time curve from time zero to infinity, calculated from AUC0-t + (Clast/lz), where Clast is the last quantifiable concentration and lz the apparent terminal rate constant - last dose (dose 13)

  BIA 6-512 pharmacokinetic parameters following the last dose (Dose 13)

  Dose 13: pre-dose and ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose

• t½ - the apparent elimination half-life, calculated from ln 2/lz - last dose (dose 13)

  BIA 6-512 pharmacokinetic parameters following the last dose (Dose 13)

  Dose 13: pre-dose and ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose

Study Arms (4)

BIA 6-512 25 mg or Placebo

EXPERIMENTAL

1 capsule of BIA 6-512 25 mg or 1 capsule of placebo.

Drug: BIA 6-512; Drug: Placebo

BIA 6-512 50 mg or Placebo

EXPERIMENTAL

1 capsule of BIA 6-512 50 mg or 1 capsule of placebo.

Drug: BIA 6-512; Drug: Placebo

BIA 6-512 100 mg or Placebo

EXPERIMENTAL

1 capsule of BIA 6-512 100 mg or 1 capsule of placebo.

Drug: BIA 6-512; Drug: Placebo

BIA 6-512 150 mg or Placebo

EXPERIMENTAL

1 capsule of BIA 6-512 150 mg or 1 capsule of placebo.

Drug: BIA 6-512; Drug: Placebo

Interventions

BIA 6-512 DRUG

The investigational products consisted of capsules containing BIA 6-512 25 mg, 50 mg, 100 mg and 150 mg. Products were administered orally, with approximately 240 mL of water in case of Doses 1 and 13, and at least 150 mL of water in case of Doses 2 to 12. First dose (Dose 1) and last dose (Dose 13) were administered in fasting of at least 8 hours and subject remained fasted until to 2.5 h post-dose. Meals were not served within 1 hour prior and 1 hour after investigational product administration in Doses 2 to 12

Also known as: Trans-resveratrol

BIA 6-512 100 mg or Placebo; BIA 6-512 150 mg or Placebo; BIA 6-512 25 mg or Placebo; BIA 6-512 50 mg or Placebo

Placebo DRUG

Matching placebo capsules

BIA 6-512 100 mg or Placebo; BIA 6-512 150 mg or Placebo; BIA 6-512 25 mg or Placebo; BIA 6-512 50 mg or Placebo

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

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 drug or food 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 or admission.
• Subjects who had acute gastrointestinal symptoms at the time of screening or admission (e.g., nausea, vomiting, diarrhoea, heartburn).
• Subjects who had used medicines within 2 weeks of first admission that, in the opinion of the investigator, may affect the safety or other study assessments.
• Subjects who had used any investigational drug or participated in any clinical trial within 2 months of their admission.
• Subjects who had donated or received any blood or blood products within the previous 2 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.

Sponsors & Collaborators

• Bial - Portela C S.A.: lead

Study Sites (1)

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

S. Mamede Do Coronado, 4745-457, Portugal

Location

MeSH Terms

Conditions

Parkinson Disease

Interventions

Resveratrol

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Stilbestrols; Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polyphenols; Phenols

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 22, 2017
• First Posted: March 28, 2017
• Study Start: May 11, 2005
• Primary Completion: July 29, 2005
• Study Completion: July 29, 2005
• Last Updated: March 28, 2017

Record last verified: 2017-03

Locations

PT (1)