- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03090724
Pharmacokinetics of BIA 5-453 and Its Metabolites
Single-dose and Steady-state Pharmacokinetics of BIA 5-453 and Its Metabolites in Healthy Male Elderly Subjects Compared With Those in Healthy Male Young Subjects
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Single-centre, open-label, parallel group, non-randomised study in 12 healthy elderly and 12 healthy younger male subjects, who participated in 2 consecutive phases:
Phase A: a single-dose phase (including a wash out period); Phase B: a multiple-dose phase during 7 days (steady state).
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Rennes, France, F-35000
- Biotrial
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
All subjects (young and elderly):
- A signed and dated informed consent form before any study-specific screening procedure is performed.
- Healthy as determined by the investigator on the basis of medical history, physical examination, clinical laboratory test results, vital signs and digital 12-lead electrocardiogram (ECG).
Non-smoker or smoker of <10 cigarettes per day as determined by history. Must be able to abstain from smoking during the inpatient stay.
Young subjects only:
Males aged between 18 and 45 years, inclusive.
Elderly subjects only:
- Males older than 65 years, inclusive. Specific inclusion criteria procedure: genotyping Since acetylation is an important BIA 5-453 metabolic pathway, NAT1 and NAT2 genotyping was required for inclusion for distinguishing between poor and faster acetylators (both could however be enrolled in the study).
Exclusion Criteria:
All subjects (young and elderly):
General
- Subjects who had participated in a clinical trial with an investigational drug within the 90 days prior to screening.
- Subjects who were likely to be noncompliant with the protocol, or who were felt to be unsuitable by the Investigator for any other reason.
- Positive serologic findings for human immunodeficiency virus (HIV) antibodies, hepatitis B surface antigen (HBsAg), and/or hepatitis C virus (HCV) antibodies.
Positive findings of urine drug screen (amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, methadone, opiates, MDMA [3,4-methylenedioxy-methamphetamine; ecstasy]).
Medical History
- Any significant cardiovascular, hepatic, renal, respiratory (e.g. childhood asthma), gastrointestinal, endocrine (e.g. diabetes), immunological, dermatological, haematological, neurological, or psychiatric disease and history thereof.
- Acute disease state (e.g., nausea, vomiting, fever, diarrhoea) within 7 days before study Day 1.
- Subjects proned to orthostatic hypotension: there was a measurement of supine blood pressure (BP) and heart rate (HR) after the subjects had been resting for at least 10 minutes, followed by standing BP and HR after 2 minutes of standing: orthostatic hypotension as defined by as a difference between supine systolic BP (SBP) and standing SBP ≥20 mmHg or a difference between supine diastolic BP (DBP) and standing DBP ≥10 mmHg.
- History of drug abuse within 1 year before study day 1.
- History of alcoholism within 1 year before day 1. Consumption of more than 50 g of ethanol per day (12.5 cL glass of 10° [10%] wine = 12 g; 4 cL of aperitif, 42° [42%] whiskey = 17 g; 25 cL glass of 3° [3%] beer = 7.5 g; 25 cL glass of 6° [6%] beer = 15 g.
- History of any clinically important drug allergy.
- Had previously received BIA 5-453. Prohibited treatments and dietary restrictions
- Consumption of any caffeine-containing products (e.g., coffee, tea, chocolate, or soda) in excess of 6 cups per day (or equivalent), of grapefruit, grapefruit-containing products, or alcoholic beverages within 24 hours before study day 1.
- Use of any over-the-counter drugs including herbal supplements (except for the occasional use of acetaminophen [paracetamol], aspirin and vitamins ≤100% recommended daily allowance) within 7 days before BIA 5-453 administration.
Donation of blood (i.e. 450 mL) within 60 days before study day 1.
Young subjects only:
General
- An automatic QTc interval reading ≥450 ms at the screening assessment. Prohibited treatments and dietary restrictions
Prohibited Treatments: use of any investigational drug within 90 days (young and elderly subjects) or prescription drug within 30 days before BIA 5-453 administration.
Elderly subjects only:
General
- An automatic QTc interval reading ≥470 ms at the screening assessment.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: BIA 5-453 (Young)
Each subject participated in the study for approximately 7 weeks. Participation included the screening evaluations within 28 days before the first administration, phase A (single dose, a 2-day inpatient period followed by 4 ambulatory visits), phase B (multiple-dose during 7 days, 6 ambulatory visits, followed by a 2-day inpatient period and by 5 ambulatory visits) and a follow-up visit 7 to 10 days after the last administration. Phase A: single-dose on Day 1, followed by a wash out period Phase B: repeated dose from Day 6 to Day 12 (7 days, steady-state) |
100 mg of BIA 5-453 (combination of two 50 mg capsules); Oral, once-daily (QD), in the morning in fasting conditions
Other Names:
|
Experimental: BIA 5-453 (Elderly)
Each subject participated in the study for approximately 7 weeks. Participation included the screening evaluations within 28 days before the first administration, phase A (single dose, a 2-day inpatient period followed by 4 ambulatory visits), phase B (multiple-dose during 7 days, 6 ambulatory visits, followed by a 2-day inpatient period and by 5 ambulatory visits) and a follow-up visit 7 to 10 days after the last administration. Phase A: single-dose on Day 1, followed by a wash out period Phase B: repeated dose from Day 6 to Day 12 (7 days, steady-state) |
100 mg of BIA 5-453 (combination of two 50 mg capsules); Oral, once-daily (QD), in the morning in fasting conditions
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Maximum observed plasma concentration (Cmax) - DAY 1
Time Frame: Day 1 pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, and 96 h post-dose
|
Day 1 pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, and 96 h post-dose
|
The time at which Cmax was observed (Tmax) - Day 1
Time Frame: Day 1 pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, and 96 h post-dose
|
Day 1 pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, and 96 h post-dose
|
The terminal half-life (t1/2) - Day 1
Time Frame: Day 1 pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, and 96 h post-dose
|
Day 1 pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, and 96 h post-dose
|
The area under the concentration-time curve from 0 to infinity (AUC0-∞) - Day 1
Time Frame: Day 1 pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, and 96 h post-dose
|
Day 1 pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, and 96 h post-dose
|
The Area Under the Curve from time 0 to 24 h post-dose (AUC0-24) - Day 1
Time Frame: Day 1 pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, and 96 h post-dose
|
Day 1 pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, and 96 h post-dose
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Maximum observed plasma concentration (Cmax) - DAY 12
Time Frame: Day 12 pre-dose, and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 120 h post-last dose
|
Day 12 pre-dose, and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 120 h post-last dose
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The time at which Cmax was observed (Tmax) - Day 12
Time Frame: Day 12 pre-dose, and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 120 h post-last dose
|
Day 12 pre-dose, and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 120 h post-last dose
|
The terminal half-life (t1/2) - Day 12
Time Frame: Day 12 pre-dose, and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 120 h post-last dose
|
Day 12 pre-dose, and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 120 h post-last dose
|
The area under the concentration-time curve from 0 to infinity (AUC0-∞) - Day 12
Time Frame: Day 12 pre-dose, and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 120 h post-last dose
|
Day 12 pre-dose, and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 120 h post-last dose
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The Area Under the Curve from time 0 to 24 h post-dose (AUC0-24) - Day 12
Time Frame: Day 12 pre-dose, and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 120 h post-last dose
|
Day 12 pre-dose, and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 120 h post-last dose
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- BIA-5453-105
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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