NCT03708146

Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of BIA 5-1058

A Double-Blind, Randomised, Placebo-Controlled, Parallel Group Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Doses of BIA 5 1058 in Healthy Volunteers

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 157 (actual)
• Sponsor: Bial - Portela C S.A. · Industry
• Sex: All
• Age: 18 Years – 55 Years
• Healthy volunteers: Accepted

Summary

This is a single centre, double-blind, randomised, placebo-controlled, parallel staggered group study of BIA 5-1058 in 11 different cohorts of 15 healthy subjects. Subjects will be randomly assigned to receive once-daily oral doses of BIA 5-1058 or matching placebo for 10 days. The primary objectives of the study are to assess the safety and tolerability of BIA 5-1058 after repeated ascending doses under fed and fasted conditions and to assess the pharmacokinetics (PK) of BIA 5-1058 after repeated ascending doses under fed conditions having matching fasting cohorts for comparison of bioavailability. It is planned that comparison cohorts will be dosed in parallel, i.e. Cohorts 1 and 2, 3 and 4, 5 and 6, 7 and 8 and 9 and 10. Cohorts may be split or dosed sequentially for logistical purposes; however, data from both comparison cohorts (e.g. Cohorts 1 and 2) must be available before dose escalation to the next dose levels.

Detailed description

Each cohort will follow the same study design. Subjects will be screened for inclusion in the study between 28 and 3 days before the first dose. Eligible subjects will be admitted 2 days before dosing (Day -2) for all regimens, and will remain resident in the clinic until 72 h after the last dose (Day 13). On Day -1, blood samples will be taken in all cohorts for PD assessments at pre-defined time points. These time points will be time matched to Day 1 PK and PD time points. Subjects in Cohorts 2, 4, 6, 8, 10 and 11 (fed cohorts) will also undergo continuous cardiac monitoring via 24 h Holter recordings on Day -1. Subjects in Cohorts 1, 3, 5, 7 and 9 will receive oral doses of BIA 5-1058 or matching placebo once daily from Day 1 to Day 10, administered in the morning of each day after a minimum of 8 h fast and will remain fasted until 4 h post-dose. Subjects in Cohorts 2, 4, 6, 8, 10 and 11 will receive oral doses of BIA 5-1058 or matching placebo once daily from Day 1 to Day 10, administered in the morning of each day, 30 minutes after the start of a moderate breakfast containing approximately 550 kcal with fat contributing approximately 150 kcal.

Conditions

• Cardiovascular Disease+Pulmonary Disease
• Pulmonary Arterial Hypertension

Interventions

Type	Name	Description
DRUG	BIA 5-1058	25 mg and 100 mg tablets; Oral, once-daily, from Day 1 to Day 10. In Cohorts 1, 3, 5, 7 and 9 (fasted), BIA 5-1058 will be orally administered in the morning after a minimum of 8 h fast. Subjects will remain fasted until 4 h post-dose and will receive lunch approximately 4 h after dosing. In Cohorts 2, 4, 6, 8 and 10 (fed), BIA 5-1058 will be orally administered in the morning after a moderate breakfast (containing approximately 550 kcal with fat contributing approximately 150 kcal). The meal should be consumed over a maximum period of 25 min, with dosing occurring 30 min after the start of the meal. Each dose will be administered with 240 mL water.
DRUG	Placebo	matching placebo tablet; Oral, once-daily, from Day 1 to Day 10. In Cohorts 1, 3, 5, 7 and 9 (fasted), placebo will be orally administered in the morning after a minimum of 8 h fast. Subjects will remain fasted until 4 h post-dose and will receive lunch approximately 4 h after dosing. In Cohorts 2, 4, 6, 8 and 10 (fed), placebo will be orally administered in the morning after a moderate breakfast (containing approximately 550 kcal with fat contributing approximately 150 kcal). The meal should be consumed over a maximum period of 25 min, with dosing occurring 30 min after the start of the meal. Each dose will be administered with 240 mL water.

Timeline

• Start date: 2018-05-28
• Primary completion: 2019-03-18
• Completion: 2019-03-18
• First posted: 2018-10-17
• Last updated: 2020-12-31

Locations

1 site across 1 country: United Kingdom