Pharmacokinetic Profile of BIA 6-512 in Healthy Elderly Subjects Versus Healthy Young Subjects

An Open-label, Parallel-group Study to Compare the Pharmacokinetic Profile in Healthy Elderly Subjects Versus Healthy Young Subjects After Single and Repeated Oral Administration of BIA 6-512 (Trans-resveratrol)

the purpose of the study was to the compare pharmacokinetic profile of BIA 6-512 in healthy elderly subjects versus healthy young subjects after single and repeated oral administration of 200 mg BIA 6-512.

Study Overview

• Status: Completed
• Conditions: Parkinson Disease
• Intervention / Treatment: Drug: 200 mg BIA 6-512

Detailed Description

Single-centre, open-label study in healthy young (18-40 years) and elderly (65 years or older) subjects. The study consisted of a single-dose phase followed by a repeated dose phase (3 times daily, at 8-h intervals). Subjects were admitted on the day prior to the first dose (Day 1). On day 1, a single dose of 200 mg BIA 6-512 (Dose 1) was administered in the morning. On day 2, the repeated dose phase started 24 h post first dosing. In the repeated dose phase (Doses 2 to 8) subjects received 200 mg BIA 6-512 every 8 hours until the morning of day 4 (approximately 72 hours post first dosing).

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Hamburg, Germany, D-22525
    • Scope International AG

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female subjects aged between 18 and 40 years, inclusive (young); or male or female subjects aged 65 years or more (elderly).
• Body mass index (BMI) between 19 and 30 kg/m2, inclusive.
• Healthy as determined by an inter¬view, pre-study medical history, physical examination, vital signs, neurological examination and 12-lead ECG; clinical laboratory test results clinically acceptable at screening and admission.
• Negative tests for HBsAg, anti-HCVAb, anti-HIV-1 Ab and anti-HIV-2 Ab at screening.
• Negative screen for drugs of abuse at screening and admission.
• Informed consent signed by the subject.
• Co-operative and available for the entire study.
• Abstinence from alcohol for 48 hours prior to admission (as stated by subject). An alcohol breath test performed at screening and at admission to the clinic had to be negative.
• Non-smokers or who smoke ≤ 10 cigarettes or equivalent per day.
• If female, in the young group: 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; and she had a negative urine pregnancy test at screening and admission.

Exclusion Criteria:

• Evidence in the subject's medical history or in the medical exa¬mina¬tion of any clinically significant respiratory, hepatic, renal, gastrointesti¬nal, haematological, lymphatic, neurological, car¬diovascu¬lar, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, endocrine, connective tissue or other significant acute or chronic abnormalities which might influence either the safety of the subject or the ab¬sorption, dis¬tribution, meta¬bolism or excretion of the active agent under investigation.
• History of relevant drug or food hypersensitivity.
• Significant infection or known inflammatory process on screening or admission.
• Acute gastrointestinal symptoms at the time of screening or admission (e.g., nausea, vomiting, diarrhoea, heartburn).
• Regular use of any medication within four weeks prior to study admission (self-medication or prescription).
• Single use of any medication (including OTC) that was not expressly permitted within two weeks prior admission to the stu¬dy.
• Abuse of alcohol (equiv¬alent to more than 35 g ethanol per day).
• Vegetarians, vegans or subjects who had medical dietary restrictions.
• History of alcoholism or drug abuse.
• Participation in a clinical investigation within two months prior to screening.
• Blood donation of more than 250 ml within two months prior to screening. Blood donation of less than 250 ml or plasma donation with¬in one month prior to screening.

• Subjects who were known or suspected:

  • not to comply with the study directives
  • not to be reliable or trustworthy
  • not to be capable of understanding and evaluating the information given to them as part of the formal information policy (informed consent), in particular regarding the risks and discomfort to which they would agree to be exposed
  • to be in such a precarious financial situation that they no longer weigh up the possible risks of their participation and the unpleasantness they may be involved in.
• If female, in the young group: she was pregnant or breast-feeding; she was of childbearing potential and she did not use an approved effective contraceptive method (double-barrier, intra-uterine device or abstinence) or she used oral contraceptives.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Young group; The study was performed in two consecutive phases: single-dose and multiple-dose. Subjects were institutionalised on Day 0, the day prior to the single-dose administration (Day 1). Single dose (dose 1) of BIA 6-512 200 mg was administered on Day 1 and subjects remained confined in the Unit until the 24 h post-dose procedures (Day 2). Then, subjects started being administered BIA 6-512 200 mg thrice-daily until the morning of Day 4 (Dose 8). Blood samples were taken at pre-determined time-points for the assay of BIA 6-512	Drug: 200 mg BIA 6-512; capsules containing BIA 6-512 200 mg was administered orally, with 240 mL of mineral water without gas at room tempera¬ture; Other Names: Trans-resveratrol
Experimental: Elderly group; The study was performed in two consecutive phases: single-dose and multiple-dose. Subjects were institutionalised on Day 0, the day prior to the single-dose administration (Day 1). Single dose (dose 1) of BIA 6-512 200 mg was administered on Day 1 and subjects remained confined in the Unit until the 24 h post-dose procedures (Day 2). Then, subjects started being administered BIA 6-512 200 mg thrice-daily until the morning of Day 4 (Dose 8). Blood samples were taken at pre-determined time-points for the assay of BIA 6-512	Drug: 200 mg BIA 6-512; capsules containing BIA 6-512 200 mg was administered orally, with 240 mL of mineral water without gas at room tempera¬ture; Other Names: Trans-resveratrol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax - the maximum observed plasma concentration (single dose)		Day 1: pre-dose 1, and ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 12 and 16 h post-dose
AUCτ- the area under the plasma concentration versus time curve over the dosing interval, calculated by the linear trapezoidal rule (Single dose)		Day 1: pre-dose 1, and ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 12 and 16 h 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. (single dose)		Day 1: pre-dose 1, and ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 12 and 16 h post-dose
Cmax - the maximum observed plasma concentration (multiple dose)	Effect of age on the BIA 6-512 pharmacokinetics	Day 2: pre-dose 2; pre-dose 3 and pre-dose 4; day 3: pre-dose 5, pre-dose 6 and pre-dose 7; day 4: pre-dose 8 and ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 12 and 16 h post-dose; day 5: 24 h after last dose (dose 8).
AUCτ - the area under the plasma concentration versus time curve over the dosing interval, calculated by the linear trapezoidal rule (multiple dose)	Effect of age on the BIA 6-512 pharmacokinetics	Day 2: pre-dose 2; pre-dose 3 and pre-dose 4; day 3: pre-dose 5, pre-dose 6 and pre-dose 7; day 4: pre-dose 8 and ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 12 and 16 h post-dose; day 5: 24 h after last dose (dose 8).
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. (multiple dose)	Effect of age on the BIA 6-512 pharmacokinetics	Day 2: pre-dose 2; pre-dose 3 and pre-dose 4; day 3: pre-dose 5, pre-dose 6 and pre-dose 7; day 4: pre-dose 8 and ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 12 and 16 h post-dose; day 5: 24 h after last dose (dose 8).

Collaborators and Investigators

• Sponsor: Bial - Portela C S.A.

Study record dates

Study Major Dates

• Study Start (Actual): January 24, 2006
• Primary Completion (Actual): March 2, 2006
• Study Completion (Actual): March 2, 2006

Study Registration Dates

• First Submitted: March 23, 2017
• First Submitted That Met QC Criteria: March 23, 2017
• First Posted (Actual): March 29, 2017

Study Record Updates

• Last Update Posted (Actual): March 30, 2017
• Last Update Submitted That Met QC Criteria: March 29, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Protective Agents; Antioxidants; Resveratrol
• Other Study ID Numbers: BIA-6512-105

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