Trial to Evaluate the Effect of Eslicarbazepine Acetate on Cardiac Repolarization

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Epilepsy

Intervention / Treatment
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* Drug: BIA 2-093
* Drug: Moxifloxacin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Sequence ABCD<br>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 | Drug: BIA 2-093<br> <br> * Other names: ESL, Eslicarbazepine acetate;Drug: Moxifloxacin<br> <br> * Other names: avalox;Drug: Placebo<br> <br> * Other names: PLC;|
| Experimental: Treatment Sequence BDAC<br>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 | Drug: BIA 2-093<br> <br> * Other names: ESL, Eslicarbazepine acetate;Drug: Moxifloxacin<br> <br> * Other names: avalox;Drug: Placebo<br> <br> * Other names: PLC;|
| Experimental: Treatment Sequence CADB<br>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 | Drug: BIA 2-093<br> <br> * Other names: ESL, Eslicarbazepine acetate;Drug: Moxifloxacin<br> <br> * Other names: avalox;Drug: Placebo<br> <br> * Other names: PLC;|
| Experimental: Treatment Sequence DCBA<br>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 | Drug: BIA 2-093<br> <br> * Other names: ESL, Eslicarbazepine acetate;Drug: Moxifloxacin<br> <br> * Other names: avalox;Drug: Placebo<br> <br> * Other names: PLC;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 |