Epilepsy
Conditions
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.
Interventions
DRUGBIA 2-093
DRUGMoxifloxacin
DRUGPlacebo
Sponsors
Bial - Portela C S.A.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | 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
| Measure | 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment Sequence ABCD 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
BIA 2-093
Moxifloxacin
Placebo | 17 |
| Treatment Sequence BDAC 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
BIA 2-093
Moxifloxacin
Placebo | 17 |
| Treatment Sequence CADB 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
BIA 2-093
Moxifloxacin
Placebo | 17 |
| Treatment Sequence DCBA 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
BIA 2-093
Moxifloxacin
Placebo | 16 |
| Total | 67 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 3 | 5 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | Treatment Sequence ABCD | Treatment Sequence BDAC | Treatment Sequence CADB | Treatment Sequence DCBA | Total |
|---|---|---|---|---|---|
| Age, Continuous | 36.2 years STANDARD_DEVIATION 7.55 | 33.6 years STANDARD_DEVIATION 6.41 | 32.6 years STANDARD_DEVIATION 7.88 | 35.8 years STANDARD_DEVIATION 7.35 | 34.5 years STANDARD_DEVIATION 7.31 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 0 Participants | 4 Participants | 1 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 13 Participants | 16 Participants | 13 Participants | 15 Participants | 57 Participants |
| Sex: Female, Male Female | 7 Participants | 9 Participants | 10 Participants | 9 Participants | 35 Participants |
| Sex: Female, Male Male | 10 Participants | 8 Participants | 7 Participants | 7 Participants | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 17 | 3 / 17 | 5 / 17 | 1 / 16 |
| serious Total, serious adverse events | 0 / 17 | 0 / 17 | 0 / 17 | 0 / 16 |
Outcome results
Primary
QTcI - QT Interval Individually Corrected for Heart Rate - Day 5
Time frame: -30 minutes (pre-dose) 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, and 23.5 hours post-dose
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BIA 2-093 1200 mg | QTcI - QT Interval Individually Corrected for Heart Rate - Day 5 | 23.5 hours | -3.36 msec | Standard Deviation 11.514 |
| BIA 2-093 1200 mg | QTcI - QT Interval Individually Corrected for Heart Rate - Day 5 | 8 hours | -2.63 msec | Standard Deviation 10.841 |
| BIA 2-093 1200 mg | QTcI - QT Interval Individually Corrected for Heart Rate - Day 5 | 4 hours | -7.72 msec | Standard Deviation 12.496 |
| BIA 2-093 1200 mg | QTcI - QT Interval Individually Corrected for Heart Rate - Day 5 | 6 hours | -4.59 msec | Standard Deviation 11.792 |
| BIA 2-093 1200 mg | QTcI - QT Interval Individually Corrected for Heart Rate - Day 5 | 5 hours | -3.54 msec | Standard Deviation 11.282 |
| BIA 2-093 1200 mg | QTcI - QT Interval Individually Corrected for Heart Rate - Day 5 | 16 hours | -3.72 msec | Standard Deviation 10.863 |
| BIA 2-093 1200 mg | QTcI - QT Interval Individually Corrected for Heart Rate - Day 5 | 1 hour | -9.34 msec | Standard Deviation 11.399 |
| BIA 2-093 1200 mg | QTcI - QT Interval Individually Corrected for Heart Rate - Day 5 | 0.5 hr | -8.05 msec | Standard Deviation 12.168 |
| BIA 2-093 1200 mg | QTcI - QT Interval Individually Corrected for Heart Rate - Day 5 | 1.5 hours | -8.70 msec | Standard Deviation 11.689 |
| BIA 2-093 1200 mg | QTcI - QT Interval Individually Corrected for Heart Rate - Day 5 | 12 hours | -0.01 msec | Standard Deviation 9.347 |
| BIA 2-093 1200 mg | QTcI - QT Interval Individually Corrected for Heart Rate - Day 5 | 2 hours | -9.48 msec | Standard Deviation 10.692 |
| BIA 2-093 1200 mg | QTcI - QT Interval Individually Corrected for Heart Rate - Day 5 | 3 hours | -8.04 msec | Standard Deviation 11.188 |
| BIA 2-093 2400 mg | QTcI - QT Interval Individually Corrected for Heart Rate - Day 5 | 2 hours | -8.31 msec | Standard Deviation 10.738 |
| BIA 2-093 2400 mg | QTcI - QT Interval Individually Corrected for Heart Rate - Day 5 | 12 hours | 0.03 msec | Standard Deviation 13.311 |
| BIA 2-093 2400 mg | QTcI - QT Interval Individually Corrected for Heart Rate - Day 5 | 23.5 hours | -0.06 msec | Standard Deviation 12.605 |
| BIA 2-093 2400 mg | QTcI - QT Interval Individually Corrected for Heart Rate - Day 5 | 4 hours | -6.16 msec | Standard Deviation 13.563 |
| BIA 2-093 2400 mg | QTcI - QT Interval Individually Corrected for Heart Rate - Day 5 | 16 hours | -4.65 msec | Standard Deviation 12.93 |
| BIA 2-093 2400 mg | QTcI - QT Interval Individually Corrected for Heart Rate - Day 5 | 1.5 hours | -8.67 msec | Standard Deviation 10.525 |
| BIA 2-093 2400 mg | QTcI - QT Interval Individually Corrected for Heart Rate - Day 5 | 6 hours | -2.64 msec | Standard Deviation 12.856 |
| BIA 2-093 2400 mg | QTcI - QT Interval Individually Corrected for Heart Rate - Day 5 | 0.5 hr | -6.15 msec | Standard Deviation 10.891 |
| BIA 2-093 2400 mg | QTcI - QT Interval Individually Corrected for Heart Rate - Day 5 | 5 hours | -1.71 msec | Standard Deviation 12.567 |
| BIA 2-093 2400 mg | QTcI - QT Interval Individually Corrected for Heart Rate - Day 5 | 8 hours | -1.36 msec | Standard Deviation 11.281 |
| BIA 2-093 2400 mg | QTcI - QT Interval Individually Corrected for Heart Rate - Day 5 | 3 hours | -8.50 msec | Standard Deviation 13.142 |
| BIA 2-093 2400 mg | QTcI - QT Interval Individually Corrected for Heart Rate - Day 5 | 1 hour | -7.34 msec | Standard Deviation 11.822 |
| Moxifloxacin 400 mg | QTcI - QT Interval Individually Corrected for Heart Rate - Day 5 | 1 hour | 3.80 msec | Standard Deviation 11.824 |
| Moxifloxacin 400 mg | QTcI - QT Interval Individually Corrected for Heart Rate - Day 5 | 5 hours | 7.07 msec | Standard Deviation 11.309 |
| Moxifloxacin 400 mg | QTcI - QT Interval Individually Corrected for Heart Rate - Day 5 | 0.5 hr | -2.77 msec | Standard Deviation 10.496 |
| Moxifloxacin 400 mg | QTcI - QT Interval Individually Corrected for Heart Rate - Day 5 | 1.5 hours | 5.30 msec | Standard Deviation 11.537 |
| Moxifloxacin 400 mg | QTcI - QT Interval Individually Corrected for Heart Rate - Day 5 | 2 hours | 6.87 msec | Standard Deviation 11.477 |
| Moxifloxacin 400 mg | QTcI - QT Interval Individually Corrected for Heart Rate - Day 5 | 3 hours | 8.49 msec | Standard Deviation 12.875 |
| Moxifloxacin 400 mg | QTcI - QT Interval Individually Corrected for Heart Rate - Day 5 | 4 hours | 10.13 msec | Standard Deviation 11.686 |
| Moxifloxacin 400 mg | QTcI - QT Interval Individually Corrected for Heart Rate - Day 5 | 6 hours | 5.83 msec | Standard Deviation 10.927 |
| Moxifloxacin 400 mg | QTcI - QT Interval Individually Corrected for Heart Rate - Day 5 | 8 hours | 5.80 msec | Standard Deviation 12.303 |
| Moxifloxacin 400 mg | QTcI - QT Interval Individually Corrected for Heart Rate - Day 5 | 12 hours | 5.85 msec | Standard Deviation 9.955 |
| Moxifloxacin 400 mg | QTcI - QT Interval Individually Corrected for Heart Rate - Day 5 | 16 hours | 5.21 msec | Standard Deviation 10.9 |
| Moxifloxacin 400 mg | QTcI - QT Interval Individually Corrected for Heart Rate - Day 5 | 23.5 hours | 2.39 msec | Standard Deviation 9.104 |
| Placebo | QTcI - QT Interval Individually Corrected for Heart Rate - Day 5 | 1.5 hours | -4.22 msec | Standard Deviation 10.432 |
| Placebo | QTcI - QT Interval Individually Corrected for Heart Rate - Day 5 | 1 hour | -4.14 msec | Standard Deviation 9.515 |
| Placebo | QTcI - QT Interval Individually Corrected for Heart Rate - Day 5 | 4 hours | -2.10 msec | Standard Deviation 9.899 |
| Placebo | QTcI - QT Interval Individually Corrected for Heart Rate - Day 5 | 12 hours | -1.44 msec | Standard Deviation 9.15 |
| Placebo | QTcI - QT Interval Individually Corrected for Heart Rate - Day 5 | 0.5 hr | -4.39 msec | Standard Deviation 9.985 |
| Placebo | QTcI - QT Interval Individually Corrected for Heart Rate - Day 5 | 6 hours | -3.10 msec | Standard Deviation 10.537 |
| Placebo | QTcI - QT Interval Individually Corrected for Heart Rate - Day 5 | 23.5 hours | -1.71 msec | Standard Deviation 9.513 |
| Placebo | QTcI - QT Interval Individually Corrected for Heart Rate - Day 5 | 16 hours | -1.41 msec | Standard Deviation 12.835 |
| Placebo | QTcI - QT Interval Individually Corrected for Heart Rate - Day 5 | 3 hours | -3.24 msec | Standard Deviation 11.178 |
| Placebo | QTcI - QT Interval Individually Corrected for Heart Rate - Day 5 | 2 hours | -5.32 msec | Standard Deviation 10.189 |
| Placebo | QTcI - QT Interval Individually Corrected for Heart Rate - Day 5 | 5 hours | -0.75 msec | Standard Deviation 10.09 |
| Placebo | QTcI - QT Interval Individually Corrected for Heart Rate - Day 5 | 8 hours | -1.77 msec | Standard Deviation 10.586 |
Secondary
QTcB - QT Interval Corrected for Heart Rate Using Bazett's Formula
Time frame: -30 minutes (pre-dose) 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, and 23.5 hours post-dose
Secondary
QTcF - QT Interval Corrected Using Fridericia's Formula
Time frame: -30 minutes (pre-dose) 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, and 23.5 hours post-dose