Trial Outcomes & Findings for Single-dose and Steady-state Pharmacokinetics of BIA 2-093 and Its Metabolites (NCT NCT02172755)

Last Updated: 2017-05-19

Results Overview

Single-dose period: Day 1 at pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours post-dose. Multiple-dose period: from Day 5 to Day 11 inclusive, early in the morning, before the daily dose (for trough levels). Day 12: pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-last dose. BIA 2-194, BIA 2-195, and oxcarbazepine are metabolites of BIA 2-093

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

30 participants

Primary outcome timeframe

Day 1 at pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours post-dose From Day 5 to Day 11 inclusive, before the daily dose (for trough levels). On Day 12, pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours p

Results posted on

2017-05-19

Participant Flow

Participant milestones

Participant milestones
Measure	Elderly Subjects 14 Elderly subjects aged 65 years or more; During the whole study, subjects were to receive a single 600 mg dose of BIA 2-093 (Phase A) followed by 600 mg BIA 2-093 once daily for 8 days in Phase B. Phase B was to begun 96 hours post-Phase A dose. BIA 2-093: During the whole study, subjects were to receive a single 600 mg dose of BIA 2-093 (Phase A) followed by 600 mg BIA 2-093 once daily for 8 days in Phase B. Phase B was to begun 96 hours post-Phase A dose.	Young Subjects 16 young subjects aged between 18 and 40 years During the whole study, subjects were to receive a single 600 mg dose of BIA 2-093 (Phase A) followed by 600 mg BIA 2-093 once daily for 8 days in Phase B. Phase B was to begun 96 hours post-Phase A dose. BIA 2-093: During the whole study, subjects were to receive a single 600 mg dose of BIA 2-093 (Phase A) followed by 600 mg BIA 2-093 once daily for 8 days in Phase B. Phase B was to begun 96 hours post-Phase A dose.
Overall Study STARTED	14	16
Overall Study COMPLETED	12	12
Overall Study NOT COMPLETED	2	4

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Single-dose and Steady-state Pharmacokinetics of BIA 2-093 and Its Metabolites

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Elderly Subjects n=14 Participants 14 Elderly subjects aged 65 years or more; During the whole study, subjects were to receive a single 600 mg dose of BIA 2-093 (Phase A) followed by 600 mg BIA 2-093 once daily for 8 days in Phase B. Phase B was to begun 96 hours post-Phase A dose. BIA 2-093: During the whole study, subjects were to receive a single 600 mg dose of BIA 2-093 (Phase A) followed by 600 mg BIA 2-093 once daily for 8 days in Phase B. Phase B was to begun 96 hours post-Phase A dose.	Young Subjects n=15 Participants 16 young subjects aged between 18 and 40 years During the whole study, subjects were to receive a single 600 mg dose of BIA 2-093 (Phase A) followed by 600 mg BIA 2-093 once daily for 8 days in Phase B. Phase B was to begun 96 hours post-Phase A dose. BIA 2-093: During the whole study, subjects were to receive a single 600 mg dose of BIA 2-093 (Phase A) followed by 600 mg BIA 2-093 once daily for 8 days in Phase B. Phase B was to begun 96 hours post-Phase A dose.	Total n=29 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	15 Participants n=7 Participants	15 Participants n=5 Participants
Age, Categorical >=65 years	14 Participants n=5 Participants	0 Participants n=7 Participants	14 Participants n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	8 Participants n=7 Participants	15 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	7 Participants n=7 Participants	14 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 1 at pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours post-dose From Day 5 to Day 11 inclusive, before the daily dose (for trough levels). On Day 12, pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours p

Outcome measures

Outcome measures
Measure	Elderly Subjects n=12 Participants 14 Elderly subjects aged 65 years or more; During the whole study, subjects were to receive a single 600 mg dose of BIA 2-093 (Phase A) followed by 600 mg BIA 2-093 once daily for 8 days in Phase B. Phase B was to begun 96 hours post-Phase A dose. BIA 2-093: During the whole study, subjects were to receive a single 600 mg dose of BIA 2-093 (Phase A) followed by 600 mg BIA 2-093 once daily for 8 days in Phase B. Phase B was to begun 96 hours post-Phase A dose.	Young Subjects n=12 Participants 16 young subjects aged between 18 and 40 years During the whole study, subjects were to receive a single 600 mg dose of BIA 2-093 (Phase A) followed by 600 mg BIA 2-093 once daily for 8 days in Phase B. Phase B was to begun 96 hours post-Phase A dose. BIA 2-093: During the whole study, subjects were to receive a single 600 mg dose of BIA 2-093 (Phase A) followed by 600 mg BIA 2-093 once daily for 8 days in Phase B. Phase B was to begun 96 hours post-Phase A dose.
Maximum Drug Concentration (Cmax) Single dose (BIA 2-194)	9469 ng/mL Standard Deviation 2284	9867 ng/mL Standard Deviation 1714
Maximum Drug Concentration (Cmax) Multiple dose (BIA 2-194)	15067 ng/mL Standard Deviation 2126	17309 ng/mL Standard Deviation 3430
Maximum Drug Concentration (Cmax) Single dose (BIA 2-195)	209 ng/mL Standard Deviation 72.1	192 ng/mL Standard Deviation 31.5
Maximum Drug Concentration (Cmax) Multiple dose (BIA 2-195)	531 ng/mL Standard Deviation 190	461 ng/mL Standard Deviation 132
Maximum Drug Concentration (Cmax) Single dose (oxcarbazepine)	76.3 ng/mL Standard Deviation 29.5	77.3 ng/mL Standard Deviation 15.6
Maximum Drug Concentration (Cmax) Multiple dose (oxcarbazepine)	135 ng/mL Standard Deviation 36.6	150 ng/mL Standard Deviation 36.6

SECONDARY outcome

Outcome measures

Outcome measures
Measure	Elderly Subjects n=12 Participants 14 Elderly subjects aged 65 years or more; During the whole study, subjects were to receive a single 600 mg dose of BIA 2-093 (Phase A) followed by 600 mg BIA 2-093 once daily for 8 days in Phase B. Phase B was to begun 96 hours post-Phase A dose. BIA 2-093: During the whole study, subjects were to receive a single 600 mg dose of BIA 2-093 (Phase A) followed by 600 mg BIA 2-093 once daily for 8 days in Phase B. Phase B was to begun 96 hours post-Phase A dose.	Young Subjects n=12 Participants 16 young subjects aged between 18 and 40 years During the whole study, subjects were to receive a single 600 mg dose of BIA 2-093 (Phase A) followed by 600 mg BIA 2-093 once daily for 8 days in Phase B. Phase B was to begun 96 hours post-Phase A dose. BIA 2-093: During the whole study, subjects were to receive a single 600 mg dose of BIA 2-093 (Phase A) followed by 600 mg BIA 2-093 once daily for 8 days in Phase B. Phase B was to begun 96 hours post-Phase A dose.
Tmax - Time of Maximum Observed Concentration Single dose (BIA 2-194)	2.96 hours Standard Deviation 1.25	3.00 hours Standard Deviation 1.81
Tmax - Time of Maximum Observed Concentration Multiple dose (BIA 2-194)	2.04 hours Standard Deviation 0.916	2.04 hours Standard Deviation 1.57
Tmax - Time of Maximum Observed Concentration Single dose (BIA 2-195)	13.6 hours Standard Deviation 5.43	11.3 hours Standard Deviation 6.57
Tmax - Time of Maximum Observed Concentration Multiple dose (BIA 2-195)	7.29 hours Standard Deviation 4.18	7.58 hours Standard Deviation 2.68
Tmax - Time of Maximum Observed Concentration Single dose (oxcarbazepine)	5.41 hours Standard Deviation 3.29	5.41 hours Standard Deviation 2.96
Tmax - Time of Maximum Observed Concentration Multiple dose (oxcarbazepine)	2.67 hours Standard Deviation 1.54	2.67 hours Standard Deviation 1.48

SECONDARY outcome

Outcome measures

Outcome measures
Measure	Elderly Subjects n=12 Participants 14 Elderly subjects aged 65 years or more; During the whole study, subjects were to receive a single 600 mg dose of BIA 2-093 (Phase A) followed by 600 mg BIA 2-093 once daily for 8 days in Phase B. Phase B was to begun 96 hours post-Phase A dose. BIA 2-093: During the whole study, subjects were to receive a single 600 mg dose of BIA 2-093 (Phase A) followed by 600 mg BIA 2-093 once daily for 8 days in Phase B. Phase B was to begun 96 hours post-Phase A dose.	Young Subjects n=12 Participants 16 young subjects aged between 18 and 40 years During the whole study, subjects were to receive a single 600 mg dose of BIA 2-093 (Phase A) followed by 600 mg BIA 2-093 once daily for 8 days in Phase B. Phase B was to begun 96 hours post-Phase A dose. BIA 2-093: During the whole study, subjects were to receive a single 600 mg dose of BIA 2-093 (Phase A) followed by 600 mg BIA 2-093 once daily for 8 days in Phase B. Phase B was to begun 96 hours post-Phase A dose.
AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point Single dose (BIA 2-194)	190521 ng.h/mL Standard Deviation 69082	174713 ng.h/mL Standard Deviation 37062
AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point Multiple dose (BIA 2-194)	288364 ng.h/mL Standard Deviation 40878	290630 ng.h/mL Standard Deviation 68649
AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point Single dose (BIA 2-195)	5738 ng.h/mL Standard Deviation 3675	3361 ng.h/mL Standard Deviation 1295
AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point Multiple dose (BIA 2-195)	15911 ng.h/mL Standard Deviation 4852	12782 ng.h/mL Standard Deviation 3722
AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point Single dose (oxcarbazepine)	1014 ng.h/mL Standard Deviation 965	577 ng.h/mL Standard Deviation 246
AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point Multiple dose (oxcarbazepine)	1508 ng.h/mL Standard Deviation 725	1490 ng.h/mL Standard Deviation 495

Adverse Events

Elderly Subjects

Serious events: 1 serious events

Other events: 11 other events

Deaths: 0 deaths

Young Subjects

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Elderly Subjects n=14 participants at risk 14 Elderly subjects aged 65 years or more; During the whole study, subjects were to receive a single 600 mg dose of BIA 2-093 (Phase A) followed by 600 mg BIA 2-093 once daily for 8 days in Phase B. Phase B was to begun 96 hours post-Phase A dose. BIA 2-093: During the whole study, subjects were to receive a single 600 mg dose of BIA 2-093 (Phase A) followed by 600 mg BIA 2-093 once daily for 8 days in Phase B. Phase B was to begun 96 hours post-Phase A dose.	Young Subjects n=15 participants at risk；n=16 participants at risk 16 young subjects aged between 18 and 40 years During the whole study, subjects were to receive a single 600 mg dose of BIA 2-093 (Phase A) followed by 600 mg BIA 2-093 once daily for 8 days in Phase B. Phase B was to begun 96 hours post-Phase A dose. BIA 2-093: During the whole study, subjects were to receive a single 600 mg dose of BIA 2-093 (Phase A) followed by 600 mg BIA 2-093 once daily for 8 days in Phase B. Phase B was to begun 96 hours post-Phase A dose.
Cardiac disorders cardiovascular collapse	7.1% 1/14 • Number of events 1	0.00% 0/16

Other adverse events

Other adverse events
Measure	Elderly Subjects n=14 participants at risk 14 Elderly subjects aged 65 years or more; During the whole study, subjects were to receive a single 600 mg dose of BIA 2-093 (Phase A) followed by 600 mg BIA 2-093 once daily for 8 days in Phase B. Phase B was to begun 96 hours post-Phase A dose. BIA 2-093: During the whole study, subjects were to receive a single 600 mg dose of BIA 2-093 (Phase A) followed by 600 mg BIA 2-093 once daily for 8 days in Phase B. Phase B was to begun 96 hours post-Phase A dose.	Young Subjects n=15 participants at risk；n=16 participants at risk 16 young subjects aged between 18 and 40 years During the whole study, subjects were to receive a single 600 mg dose of BIA 2-093 (Phase A) followed by 600 mg BIA 2-093 once daily for 8 days in Phase B. Phase B was to begun 96 hours post-Phase A dose. BIA 2-093: During the whole study, subjects were to receive a single 600 mg dose of BIA 2-093 (Phase A) followed by 600 mg BIA 2-093 once daily for 8 days in Phase B. Phase B was to begun 96 hours post-Phase A dose.
General disorders Tiredness	57.1% 8/14	53.3% 8/15
Nervous system disorders Headache	35.7% 5/14	26.7% 4/15
Nervous system disorders Dizziness	0.00% 0/14	20.0% 3/15
Nervous system disorders Concentration impaired	7.1% 1/14	6.7% 1/15
Nervous system disorders Drowsiness	0.00% 0/14	6.7% 1/15
Nervous system disorders Head pressure	0.00% 0/14	6.7% 1/15
Nervous system disorders Vision blurred	7.1% 1/14	0.00% 0/15
Gastrointestinal disorders Dry mouth	28.6% 4/14	20.0% 3/15
Gastrointestinal disorders Nausea	14.3% 2/14	6.7% 1/15
Gastrointestinal disorders Constipation	7.1% 1/14	0.00% 0/15
Gastrointestinal disorders Diarrhoea	7.1% 1/14	6.7% 1/15
Gastrointestinal disorders Nausea with vomiting	0.00% 0/14	0.00% 0/15
Skin and subcutaneous tissue disorders Itching	7.1% 1/14	6.7% 1/15
Skin and subcutaneous tissue disorders Exanthema	7.1% 1/14	6.7% 1/15
Psychiatric disorders Decrease activity	7.1% 1/14	0.00% 0/15
Respiratory, thoracic and mediastinal disorders Sinus pressure	0.00% 0/14	6.7% 1/15

Additional Information

Head of Clinical Research

Bial - Portela & Cª, S.A.

Phone: +351 229 866 100

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER