Trial to Evaluate the Effect of Eslicarbazepine Acetate on Cardiac Repolarization

Phase 1

Completed

Conditions: Epilepsy

Interventions: Drug: BIA 2-093
Drug: Moxifloxacin
Drug: Placebo

Registration Number: NCT02283788

Lead Sponsor: Bial - Portela C S.A.

Brief Summary: A randomized, double-blind, placebo-controlled and open label active-controlled, 4 period crossover trial to evaluate the effect of eslicarbazepine acetate on cardiac repolarization in healthy adult men and women

Detailed Description: The purpose of this randomized, double-blind, placebo-controlled and open label active-controlled, 4 period crossover study was to evaluate the effect of therapeutic and supra-therapeutic doses of eslicarbazepine acetate on the placebo corrected time-matched change from baseline using individually corrected QT (QTcI) interval durations in adult healthy volunteers.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 67

Inclusion Criteria

Be a healthy male or female 18 to 45 years of age. Women were required to be postmenopausal (more than 12 months since last period); surgically sterile (hysterectomy or tubal ligation at least 6 months prior to enrollment); using an intrauterine device; or double barrier (i.e. diaphragm or spermicide plus male condom) non-hormonal contraceptive therapy for the duration of the trial and were required to have a negative pregnancy test at screening and upon each check-in to the study facility.
Have a BMI within the range of 18-30 kg/m2.
Be able to communicate effectively with the study personnel.
Have no significant disease or abnormal laboratory values as determined by medical history, physical examination or laboratory evaluations, conducted at the screening visit and on each admission to the clinic.
Have a normal 12-lead electrocardiogram, without any clinically significant abnormalities of rate, rhythm or conduction.
Be nonsmokers defined as not having smoked in the past 6 months.
Be adequately informed of the nature and risks of the study and give written informed consent prior to study entry.

Exclusion Criteria

Known hypersensitivity or allergy to moxifloxacin, eslicarbazepine acetate or related compounds such as carbamazepine, oxcarbazepine, or licarbazepine.
Women who were pregnant or breast feeding.
Any disease or condition (medical or surgical) which, in the opinion of the investigator, might compromise the hematologic, cardiovascular, pulmonary, renal, gastrointestinal, hepatic, or central nervous system; or other conditions that may interfere with the absorption, distribution, metabolism or excretion of study drug, or placed the subject at increased risk.
A sustained supine systolic blood pressure > 140 mmHg or <100mm Hg or a diastolic blood pressure > 95 mmHg at screening or baseline.
A resting ECG heart rate of <50 bpm or >100 bpm.

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Treatment Sequence CADB	BIA 2-093	A - BIA 2-093 1200 mg once daily × 5 days B - BIA 2-093 2400 mg once daily × 5 days C - Moxifloxacin 400 mg × 1 dose D - placebo once daily × 5 days
Treatment Sequence CADB	Placebo	A - BIA 2-093 1200 mg once daily × 5 days B - BIA 2-093 2400 mg once daily × 5 days C - Moxifloxacin 400 mg × 1 dose D - placebo once daily × 5 days
Treatment Sequence BDAC	Placebo	A - BIA 2-093 1200 mg once daily × 5 days B - BIA 2-093 2400 mg once daily × 5 days C - Moxifloxacin 400 mg × 1 dose D - placebo once daily × 5 days
Treatment Sequence ABCD	Placebo	A - BIA 2-093 1200 mg once daily × 5 days B - BIA 2-093 2400 mg once daily × 5 days C - Moxifloxacin 400 mg × 1 dose D - placebo once daily × 5 days
Treatment Sequence ABCD	BIA 2-093	A - BIA 2-093 1200 mg once daily × 5 days B - BIA 2-093 2400 mg once daily × 5 days C - Moxifloxacin 400 mg × 1 dose D - placebo once daily × 5 days
Treatment Sequence BDAC	BIA 2-093	A - BIA 2-093 1200 mg once daily × 5 days B - BIA 2-093 2400 mg once daily × 5 days C - Moxifloxacin 400 mg × 1 dose D - placebo once daily × 5 days
Treatment Sequence DCBA	BIA 2-093	A - BIA 2-093 1200 mg once daily × 5 days B - BIA 2-093 2400 mg once daily × 5 days C - Moxifloxacin 400 mg × 1 dose D - placebo once daily × 5 days
Treatment Sequence DCBA	Placebo	A - BIA 2-093 1200 mg once daily × 5 days B - BIA 2-093 2400 mg once daily × 5 days C - Moxifloxacin 400 mg × 1 dose D - placebo once daily × 5 days
Treatment Sequence ABCD	Moxifloxacin	A - BIA 2-093 1200 mg once daily × 5 days B - BIA 2-093 2400 mg once daily × 5 days C - Moxifloxacin 400 mg × 1 dose D - placebo once daily × 5 days
Treatment Sequence BDAC	Moxifloxacin	A - BIA 2-093 1200 mg once daily × 5 days B - BIA 2-093 2400 mg once daily × 5 days C - Moxifloxacin 400 mg × 1 dose D - placebo once daily × 5 days
Treatment Sequence CADB	Moxifloxacin	A - BIA 2-093 1200 mg once daily × 5 days B - BIA 2-093 2400 mg once daily × 5 days C - Moxifloxacin 400 mg × 1 dose D - placebo once daily × 5 days
Treatment Sequence DCBA	Moxifloxacin	A - BIA 2-093 1200 mg once daily × 5 days B - BIA 2-093 2400 mg once daily × 5 days C - Moxifloxacin 400 mg × 1 dose D - placebo once daily × 5 days

Primary Outcome Measures

Name	Time	Method
QTcI - QT Interval Individually Corrected for Heart Rate - Day 5	-30 minutes (pre-dose) 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, and 23.5 hours post-dose

Secondary Outcome Measures

Name	Time	Method
QTcF - QT Interval Corrected Using Fridericia's Formula	-30 minutes (pre-dose) 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, and 23.5 hours post-dose
QTcB - QT Interval Corrected for Heart Rate Using Bazett's Formula	-30 minutes (pre-dose) 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, and 23.5 hours post-dose