Absorption, Distribution, Metabolism and Excretion of [14C]- Labeled BIA 5-453 and Metabolites

An Open-label Study in Healthy Male Subjects to Assess the Absorption, Distribution, Metabolism and Excretion of [14C]-Labeled BIA 5-453 and Metabolites Following a Single-dose Oral Administration

The purpose of this study is to:

To determine the rate and routes of excretion of BIA 5-453 and the mass balance in urine and faeces

Study Overview

• Status: Completed
• Conditions: Hypertension; Congestive Heart Failure
• Intervention / Treatment: Drug: BIA-5-453

Detailed Description

Monocentre, open, non-placebo-controlled, single-group, single-dose study Safety measurements (12-lead ECG, vital signs, blood chemistry and haematology) will be conducted before and after the study, adverse events will be monitored throughout the study.

Subjects should be hospitalized the day before the administration until 264 hours thereafter.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 1

Contacts and Locations

Study Locations

• Switzerland
  • Allschwil, Switzerland, CH-4123
    • Swiss Pharma Contract Ltd.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Healthy Caucasian male subjects, 40-55 years of age.
• Sitting blood pressure and pulse rate within a clinically acceptable range for the purposes of the study, i.e.: BP: 100 160 mmHg systolic, 50 95 mmHg diastolic and pulse rate: 50 100 bpm. Blood pressure and pulse will be measured after 3 minutes resting in a sitting position.
• Subject body mass index must be between 18 and 28 kg/m2
• Normal 12-lead ECG
• Ability to communicate well with the investigator and comply with the requirements of the entire study.
• The subject has given his written informed consent to participate in the study.

Exclusion Criteria:

• History of serious adverse reactions or hypersensitivity to any drug.
• Presence or history of allergies requiring acute or chronic treatment (except seasonal allergic rhinitis).
• History of alcohol or drug abuse in the last 5 years.
• Abnormal physical findings of clinical significance at the screening examination or baseline which would interfere with the objectives of the study.
• Need of any prescription medication within 14 days prior to the administration of the drug and/or nonprescription medication within 7 days prior to the administration of the drug.
• Participation in other clinical trials during the previous month in which an investigational drug or a commercially available drug was tested.
• Loss of 500 mL blood or more during the 3 month period before the study, e.g., as a donor.
• Existence of any surgical or medical condition which might interfere with the absorption, distribution, metabolism or excretion of the drug, i.e., impaired renal or hepatic function, diabetes mellitus, cardiovascular abnormalities, chronic symptoms of pronounced constipation or diarrhoea or conditions associated with total or partial obstruction of the urinary tract.
• Symptoms of a significant somatic or mental illness in the 4 week period preceding drug administration.
• History of hepatitis B and / or C and / or positive serology results which indicate the presence of hepatitis B and / or C.
• Positive results from the HIV serology.
• Clinically significant abnormal laboratory values (as determined by the Principal Investigator) at the screening evaluation, however, liver parameters (SGPT, SGOT) values must be within the normal range.
• Positive results of the drug screening.
• Known hypersensitivity to BIA 5-453.
• Heavy smokers, i.e., more than 10 cigarettes per day
• Exposure to artificial ionizing radiation in the last 12 months (e.g., x-ray investigation)
• Subject who had more than 4 flights (with more than 2 hours flight time) within the last year prior to the administration of the drug

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Etamicastat; Single administration. 100 μCi/ 3.7 MBq 14C labeled BIA 5-453 50 mg, hard gelatina capsules	Drug: BIA-5-453; Each subject will receive a single oral dose of 100 μCi/ 3.7 MBq 14C labeled BIA 5-453 (600 mg).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
urinary excretion of BIA 5-453 associated radioactivity	following a single 600 mg oral dose labeled with 98 μCi of [14C]	pre-dose, then it was collected from 0-4, 4-8, 8-24, 24-48, 48-72, 72-120, 120-168, 168-216, and 216-264 hours post-dose.
faecal excretion of BIA 5-453 associated radioactivity	baseline period. Following dose, each faeces sample was collected during the 264 hours post-dose period.	following a single 600 mg oral dose labeled with 98 μCi of [14C]
amount of BIA 5-453 associated radioactivity present in the expired air	following a single 600 mg oral dose labeled with 98 μCi of [14C]	baseline, 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 4h 6h, 8h, 12h and 24h post-dose

Collaborators and Investigators

• Sponsor: Bial - Portela C S.A.

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (Actual): October 1, 2008
• Study Completion (Actual): October 1, 2008

Study Registration Dates

• First Submitted: January 5, 2017
• First Submitted That Met QC Criteria: January 6, 2017
• First Posted (Estimate): January 9, 2017

Study Record Updates

• Last Update Posted (Estimate): January 9, 2017
• Last Update Submitted That Met QC Criteria: January 6, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: BIA-5453-103

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED