Trial Outcomes & Findings for Safety, Tolerability, Pharmacokinetic, Including Food Interaction, and Pharmacodynamic Profile of BIA 5-1058. (NCT NCT02151994)

NCT ID: NCT02151994

Last Updated: 2016-01-05

Results Overview

Just before drug administration and twice daily until 72 h after (last) drug administration, subjects were asked non-leading questions to determine the occurrence of AEs. Subjects were asked in general terms about any AEs at regular intervals during each study period. In addition, all AEs reported spontaneously during the course of the study were recorded. All answers were assessed by the Medical Investigator (MI), coded using the Medical Dictionary for Regulatory Activities (MedDRA; Version 14.0) and recorded in the AEs Record. The intensity of the AEs was rated as "mild", "moderate" or "severe" and the relationship between the AEs and the study medication was indicated as "not related", "unlikely", "possible", "probable" or ''definite".

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

124 participants

Primary outcome timeframe

Just before drug administration and twice daily until 72 h after (last) drug administration

Results posted on

2016-01-05

Participant Flow

Study period : Date of first screening to last follow-up: 03 March 2011 - 13 January 2012;

Participant milestones

Participant milestones
Measure	Placebo Placebo : visually matching active medication	5 mg BIA 5-1058 (5, 25 and 100 mg) tablets SAD part: Single dose of BIA 5-1058 (n=6) or matching placebo (n=2) on Day 1, at the following dose levels: 5, 25, 50, 100, 200, 400, 800, 1600 and 2400 mg. Escalation to the next higher dose and any dose adjustments of the next dose levels were based on safety and tolerability results of the previously administered dose and available PK data of previous dose groups.	25 mg BIA 5-1058 (5, 25 and 100 mg) tablets SAD part: Single dose of BIA 5-1058 (n=6) or matching placebo (n=2) on Day 1, at the following dose levels: 5, 25, 50, 100, 200, 400, 800, 1600 and 2400 mg. Escalation to the next higher dose and any dose adjustments of the next dose levels were based on safety and tolerability results of the previously administered dose and available PK data of previous dose groups.	50 mg BIA 5-1058 (5, 25 and 100 mg) tablets SAD part: Single dose of BIA 5-1058 (n=6) or matching placebo (n=2) on Day 1, at the following dose levels: 5, 25, 50, 100, 200, 400, 800, 1600 and 2400 mg. Escalation to the next higher dose and any dose adjustments of the next dose levels were based on safety and tolerability results of the previously administered dose and available PK data of previous dose groups. MAD part: Multiple doses of BIA 5-1058 (n=6) or matching placebo (n=2) once daily on Days 1 to 10, at the following dose levels: 50, 100, 200, 400 and 1200 mg.	100 mg BIA 5-1058 (5, 25 and 100 mg) tablets SAD part: Single dose of BIA 5-1058 (n=6) or matching placebo (n=2) on Day 1, at the following dose levels: 5, 25, 50, 100, 200, 400, 800, 1600 and 2400 mg. Escalation to the next higher dose and any dose adjustments of the next dose levels were based on safety and tolerability results of the previously administered dose and available PK data of previous dose groups. MAD part: Multiple doses of BIA 5-1058 (n=6) or matching placebo (n=2) once daily on Days 1 to 10, at the following dose levels: 50, 100, 200, 400 and 1200 mg.	200 mg BIA 5-1058 (5, 25 and 100 mg) tablets SAD part: Single dose of BIA 5-1058 (n=6) or matching placebo (n=2) on Day 1, at the following dose levels: 5, 25, 50, 100, 200, 400, 800, 1600 and 2400 mg. Escalation to the next higher dose and any dose adjustments of the next dose levels were based on safety and tolerability results of the previously administered dose and available PK data of previous dose groups. MAD part: Multiple doses of BIA 5-1058 (n=6) or matching placebo (n=2) once daily on Days 1 to 10, at the following dose levels: 50, 100, 200, 400 and 1200 mg.	400 mg BIA 5-1058 (5, 25 and 100 mg) tablets SAD part: Single dose of BIA 5-1058 (n=6) or matching placebo (n=2) on Day 1, at the following dose levels: 5, 25, 50, 100, 200, 400, 800, 1600 and 2400 mg. Escalation to the next higher dose and any dose adjustments of the next dose levels were based on safety and tolerability results of the previously administered dose and available PK data of previous dose groups. MAD part: Multiple doses of BIA 5-1058 (n=6) or matching placebo (n=2) once daily on Days 1 to 10, at the following dose levels: 50, 100, 200, 400 and 1200 mg.	800 mg BIA 5-1058 (5, 25 and 100 mg) tablets SAD part: Single dose of BIA 5-1058 (n=6) or matching placebo (n=2) on Day 1, at the following dose levels: 5, 25, 50, 100, 200, 400, 800, 1600 and 2400 mg. Escalation to the next higher dose and any dose adjustments of the next dose levels were based on safety and tolerability results of the previously administered dose and available PK data of previous dose groups.	1200 mg BIA 5-1058 (5, 25 and 100 mg) tablets MAD part: Multiple doses of BIA 5-1058 (n=6) or matching placebo (n=2) once daily on Days 1 to 10, at the following dose levels: 50, 100, 200, 400 and 1200 mg.	1600 mg BIA 5-1058 (5, 25 and 100 mg) tablets SAD part: Single dose of BIA 5-1058 (n=6) or matching placebo (n=2) on Day 1, at the following dose levels: 5, 25, 50, 100, 200, 400, 800, 1600 and 2400 mg. Escalation to the next higher dose and any dose adjustments of the next dose levels were based on safety and tolerability results of the previously administered dose and available PK data of previous dose groups.	2400 mg BIA 5-1058 (5, 25 and 100 mg) tablets SAD part: Single dose of BIA 5-1058 (n=6) or matching placebo (n=2) on Day 1, at the following dose levels: 5, 25, 50, 100, 200, 400, 800, 1600 and 2400 mg. Escalation to the next higher dose and any dose adjustments of the next dose levels were based on safety and tolerability results of the previously administered dose and available PK data of previous dose groups.	400 mg Fasted BIA 5-1058 (5, 25 and 100 mg) tablets FE part: A single dose of 400 mg BIA 5-1058 on Day 1 under fasted (one period) and fed (one period) conditions.	400 mg Fed BIA 5-1058 (5, 25 and 100 mg) tablets FE part: A single dose of 400 mg BIA 5-1058 on Day 1 under fasted (one period) and fed (one period) conditions.
Single Ascending Dose (SAD) STARTED	18	6	6	6	6	6	6	6	0	6	6	0	0
Single Ascending Dose (SAD) COMPLETED	18	6	6	6	6	6	6	6	0	6	6	0	0
Single Ascending Dose (SAD) NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0
Multiple Ascending Dose (MAD) STARTED	10	0	0	6	6	6	6	0	6	0	0	0	0
Multiple Ascending Dose (MAD) COMPLETED	10	0	0	6	6	6	6	0	6	0	0	0	0
Multiple Ascending Dose (MAD) NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0
Food Effect (FE): Fasted STARTED	0	0	0	0	0	0	0	0	0	0	0	12	0
Food Effect (FE): Fasted COMPLETED	0	0	0	0	0	0	0	0	0	0	0	12	0
Food Effect (FE): Fasted NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0
Food Effect (FE): Fed STARTED	0	0	0	0	0	0	0	0	0	0	0	0	12
Food Effect (FE): Fed COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	12
Food Effect (FE): Fed NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Safety, Tolerability, Pharmacokinetic, Including Food Interaction, and Pharmacodynamic Profile of BIA 5-1058.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Single Ascending Dose (SAD) n=72 Participants This part consisted of an eligibility screening period, one study period involving administration of single doses of BIA 5-1058 or placebo according to a randomised design, and a follow-up period. Nine sequential groups of 8 healthy young male subjects were dosed. Within each group, 6 subjects were randomised to receive BIA 5-1058 and 2 subjects were randomised to receive placebo.	Multiple Ascending Dose (MAD) n=40 Participants This part consisted of an eligibility screening period, one study period involving administration of multiple doses of BIA 5-1058 or placebo once daily for 10 days, and a follow-up period. Five sequential groups of 8 healthy young male subjects were dosed. Within each group, 6 subjects were randomised to receive BIA 5-1058 and 2 subjects were randomised to receive placebo.	Food Interaction (Food Effect, FE) Analysis n=12 Participants This part consisted of an eligibility screening period, an open-label two-way crossover study period, and a follow-up period. One group of 12 subjects received single doses of 400 mg BIA 5-1058 during 2 treatment periods, once after having fasted overnight and once after consumption of a high fat breakfast. Each treatment was separated by a period of at least 7 days. The treatment sequence was determined by randomisation.	Total n=124 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	72 Participants n=5 Participants	38 Participants n=7 Participants	12 Participants n=5 Participants	122 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Sex: Female, Male Male	72 Participants n=5 Participants	40 Participants n=7 Participants	12 Participants n=5 Participants	124 Participants n=4 Participants

PRIMARY outcome

Timeframe: Just before drug administration and twice daily until 72 h after (last) drug administration

Outcome measures

Outcome measures
Measure	Placebo n=18 Participants Placebo : visually matching active medication	5 mg n=6 Participants BIA 5-1058 (5, 25 and 100 mg) tablets	25 mg n=6 Participants BIA 5-1058 (5, 25 and 100 mg) tablets	50 mg n=6 Participants BIA 5-1058 (5, 25 and 100 mg) tablets	100 mg n=6 Participants BIA 5-1058 (5, 25 and 100 mg) tablets	200 mg n=6 Participants BIA 5-1058 (5, 25 and 100 mg) tablets	400 mg n=6 Participants BIA 5-1058 (5, 25 and 100 mg) tablets	800 mg n=6 Participants BIA 5-1058 (5, 25 and 100 mg) tablets	1600 mg n=6 Participants BIA 5-1058 (5, 25 and 100 mg) tablets	2400 mg n=6 Participants BIA 5-1058 (5, 25 and 100 mg) tablets
Percentage (%) of Subjects With Treatment-Emergent Adverse Event (TEAE) Related to Study Medication (SM) - Single Ascending Dose (SAD) Period	28 % of subject with TEAEs related to SM	0 % of subject with TEAEs related to SM	0 % of subject with TEAEs related to SM	0 % of subject with TEAEs related to SM	0 % of subject with TEAEs related to SM	0 % of subject with TEAEs related to SM	17 % of subject with TEAEs related to SM	17 % of subject with TEAEs related to SM	0 % of subject with TEAEs related to SM	67 % of subject with TEAEs related to SM

PRIMARY outcome

Timeframe: Just before drug administration and twice daily until 72 h after (last) drug administration

Population: No drug-related TEAEs were reported for the dose levels of 50 mg md and 400 mg md.

Outcome measures

Outcome measures
Measure	Placebo n=10 Participants Placebo : visually matching active medication	5 mg n=6 Participants BIA 5-1058 (5, 25 and 100 mg) tablets	25 mg n=6 Participants BIA 5-1058 (5, 25 and 100 mg) tablets	50 mg n=6 Participants BIA 5-1058 (5, 25 and 100 mg) tablets	100 mg n=6 Participants BIA 5-1058 (5, 25 and 100 mg) tablets	200 mg n=6 Participants BIA 5-1058 (5, 25 and 100 mg) tablets	400 mg BIA 5-1058 (5, 25 and 100 mg) tablets	800 mg BIA 5-1058 (5, 25 and 100 mg) tablets	1600 mg BIA 5-1058 (5, 25 and 100 mg) tablets	2400 mg BIA 5-1058 (5, 25 and 100 mg) tablets
Percentage (%) of Subjects With Treatment-Emergent Adverse Event (TEAE) Related to Study Medication (SM) - Multiple Ascending Dose (MAD) Period	30 % of subject with TEAEs related to SM	0 % of subject with TEAEs related to SM	50 % of subject with TEAEs related to SM	33 % of subject with TEAEs related to SM	0 % of subject with TEAEs related to SM	33 % of subject with TEAEs related to SM	—	—	—	—

PRIMARY outcome

Timeframe: Just before drug administration and twice daily until 72 h after (last) drug administration