Pharmacokinetics of BIA 5-453 and Its Metabolites

NCT03090724 | Completed Phase 1

• 1 other identifier: BIA-5453-105
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study was to assess the effects of age on the pharmacokinetic (PK) profile of BIA 5-453 and its metabolites.

Conditions

Hypertension; Chronic Heart Failure

Outcome Measures

Primary Outcomes (10)

• Maximum observed plasma concentration (Cmax) - DAY 1

  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

  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

  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

  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

  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

• Maximum observed plasma concentration (Cmax) - DAY 12

  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 time at which Cmax was observed (Tmax) - Day 12

  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

  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

  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 Curve from time 0 to 24 h post-dose (AUC0-24) - Day 12

  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

Study Arms (2)

BIA 5-453 (Young)

EXPERIMENTAL

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)

Drug: BIA 5-453

BIA 5-453 (Elderly)

EXPERIMENTAL

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)

Drug: BIA 5-453

Interventions

BIA 5-453 DRUG

100 mg of BIA 5-453 (combination of two 50 mg capsules); Oral, once-daily (QD), in the morning in fasting conditions

Also known as: Etamicastat

BIA 5-453 (Elderly); BIA 5-453 (Young)

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Young subjects only: Males aged between 18 and 45 years, inclusive. Elderly subjects only: Males older than 65 years, inclusive.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

You may not qualify if:

• 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.

Sponsors & Collaborators

• Bial - Portela C S.A.: lead

Study Sites (1)

Biotrial

Rennes, F-35000, France

Location

MeSH Terms

Conditions

Hypertension

Interventions

etamicastat

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 20, 2017
• First Posted: March 27, 2017
• Study Start: June 13, 2008
• Primary Completion: August 12, 2008
• Study Completion: August 12, 2008
• Last Updated: March 27, 2017

Record last verified: 2017-03

Locations

FR (1)