Epilepsy
Conditions
Keywords
Anticonvulsant
Brief summary
Randomized, double-blind, placebo-controlled, sequential multiple ascending dose study to determine a maximum tolerated dose
Detailed description
This study was designed as a randomized, double-blind, placebo-controlled, sequential multiple ascending dose study to assess the safety and pharmacokinetics of supratherapeutic doses of eslicarbazepine acetate in 32 healthy adult male and female subjects, with 8 subjects per treatment group. In each study group, subjects were to receive single doses of eslicarbazepine acetate or placebo once daily for 5 days. A series of screening evaluations was performed within a 21-day period prior to the first dose of study medication in order to determine the eligibility of prospective study participants for the trial. Eligible subjects reported to the clinic on Day -1 prior to study medication administration and remained in the clinic until clinic discharge on Day 7. Plasma and urine samples were collected throughout the study to determine the pharmacokinetics of eslicarbazepine acetate and its metabolites.
Interventions
DRUGPlacebo
Matching placebo tablets for oral administration
DRUGBIA 2-093 3000 mg once daily
Eslicarbazepine acetate 600 mg tablets for oral administration
DRUGBIA 2-093 3600 mg once daily
Eslicarbazepine acetate 600 mg tablets for oral administration
Sponsors
Bial - Portela C S.A.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* 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. Female subjects were required to have a negative pregnancy test at screening and upon check-in to the study facility. * BMI within the range of 18-30 kg/m2. * Ability to communicate effectively with the study personnel. * No significant disease or abnormal laboratory values as determined by medical history, physical examination or laboratory evaluations, conducted at the screening visit and on admission to the clinic. * Normal 12-lead electrocardiogram, without any clinically significant abnormalities of rate, rhythm or conduction. * Nonsmokers defined as not having smoked in the past 6 months. * Subjects were to be adequately informed of the nature and risks of the study and were required to provide written informed consent prior to study entry.
Exclusion criteria
* Known hypersensitivity or allergy to 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, had the potential to compromise the hematologic, cardiovascular, pulmonary, renal, gastrointestinal, hepatic, or central nervous system; or other conditions that could interfere with the absorption, distribution, metabolism or excretion of study drug, or would place the subject at increased risk. * A sustained supine systolic blood pressure \> 140 mmHg or \<100mmHg or a diastolic blood pressure \> 95 mmHg at screening or baseline. * A resting ECG heart rate of \<50 bpm or \>100 bpm. * An abnormal screening ECG indicating a second- or third-degree AV block, or one or more of the following: QRS \> 110 milliseconds (msec), QTc (Fridericia correction) \> 450 msec, PR interval \> 240 msec. Any rhythm other than sinus rhythm, which was interpreted by the Investigator to be clinically significant. * The presence of abnormal laboratory values which were considered clinically significant. * Positive screen for Hepatitis B (HbsAg, Hepatitis B Surface Antigen), Hepatitis C (anti HCV, Hepatitis C Antibody), or HIV (anti-HIV 1 or 2). * Receipt of an investigational drug within a period of 30 days prior to enrollment in the study. * Receipt of any drug therapy, including hormonal contraceptives, within 2 weeks prior to administration of the first dose of any study-related treatment. This exclusion was extended to 4 weeks for any drugs known to induce or inhibit hepatic drug metabolism. * Consumption of alcohol within 48 hours prior to dose administration or during any in-patient period. * A positive urine drug screen including ethanol, cocaine, THC, barbiturates, amphetamines, benzodiazepines, and opiates. * Any history of alcohol abuse, illicit drug use, significant mental illness, physical dependence to any opioid, or any history of drug abuse or addiction. * A history of difficulty with donating blood. * Donation of blood or blood products within 45 days prior to enrollment. * Subjects with, or with a history of, additional risk factors for Torsades de Points (e.g., heart failure, hypokalemia), or a family history of long QT syndrome or family history of sudden death.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Adverse Events Reported | 2 days | Safety was evaluated through the recording and monitoring of adverse events |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Matching placebo tablets for oral administration
Placebo: Matching placebo tablets for oral administration | 4 |
| BIA 2-093 3000 mg Once Daily Subjects in Cohort 2 received a dose of 3000 mg once daily (5 x 600 mg eslicarbazepine acetate tablets)
BIA 2-093 3000 mg once daily: Eslicarbazepine acetate 600 mg tablets for oral administration | 6 |
| BIA 2-093 3600 mg Once Daily Subjects in Cohort 1 received a dose of 3600 mg once daily (6 x 600 mg eslicarbazepine acetate tablets)
BIA 2-093 3600 mg once daily: Eslicarbazepine acetate 600 mg tablets for oral administration | 6 |
| Total | 16 |
Baseline characteristics
| Characteristic | Placebo | BIA 2-093 3000 mg Once Daily | BIA 2-093 3600 mg Once Daily | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 6 Participants | 6 Participants | 16 Participants |
| Sex: Female, Male Female | 0 Participants | 4 Participants | 4 Participants | 8 Participants |
| Sex: Female, Male Male | 4 Participants | 2 Participants | 2 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 6 | 6 / 6 | 1 / 4 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 4 |
Outcome results
Primary
Number of Adverse Events Reported
Safety was evaluated through the recording and monitoring of adverse events
Time frame: 2 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BIA 2-093 3000 mg Once Daily | Number of Adverse Events Reported | Eye AE | 1 Number of adverse events reported |
| BIA 2-093 3000 mg Once Daily | Number of Adverse Events Reported | General and Administration Site Conditions AE | 4 Number of adverse events reported |
| BIA 2-093 3000 mg Once Daily | Number of Adverse Events Reported | Nervous system AE | 6 Number of adverse events reported |
| BIA 2-093 3000 mg Once Daily | Number of Adverse Events Reported | Gastrointestinal AE | 5 Number of adverse events reported |
| BIA 2-093 3000 mg Once Daily | Number of Adverse Events Reported | Skin and Subcutaneous Tissue AE | 1 Number of adverse events reported |
| BIA 2-093 3600 mg Once Daily | Number of Adverse Events Reported | General and Administration Site Conditions AE | 1 Number of adverse events reported |
| BIA 2-093 3600 mg Once Daily | Number of Adverse Events Reported | Nervous system AE | 6 Number of adverse events reported |
| BIA 2-093 3600 mg Once Daily | Number of Adverse Events Reported | Gastrointestinal AE | 4 Number of adverse events reported |
| BIA 2-093 3600 mg Once Daily | Number of Adverse Events Reported | Eye AE | 1 Number of adverse events reported |
| BIA 2-093 3600 mg Once Daily | Number of Adverse Events Reported | Skin and Subcutaneous Tissue AE | 0 Number of adverse events reported |
| Placebo | Number of Adverse Events Reported | Skin and Subcutaneous Tissue AE | 0 Number of adverse events reported |
| Placebo | Number of Adverse Events Reported | Eye AE | 0 Number of adverse events reported |
| Placebo | Number of Adverse Events Reported | Nervous system AE | 1 Number of adverse events reported |
| Placebo | Number of Adverse Events Reported | General and Administration Site Conditions AE | 0 Number of adverse events reported |
| Placebo | Number of Adverse Events Reported | Gastrointestinal AE | 1 Number of adverse events reported |