A Sequential Multiple Ascending Dose Study of the Safety and Pharmacokinetics of Eslicarbazepine Acetate in Adult Healthy Volunteers
Condition: Epilepsy
MeSH terms: Epilepsy
Intervention: Placebo; BIA 2-093 3000 mg once daily; BIA 2-093 3600 mg once daily
Intervention description: Matching placebo tablets for oral administration; Eslicarbazepine acetate 600 mg tablets for oral administration; Eslicarbazepine acetate 600 mg tablets for oral administration
Intervention MeSH terms: Eslicarbazepine acetate
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 16.0
Sex: All
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Anticonvulsant

Summary:

      Randomized, double-blind, placebo-controlled, sequential multiple ascending dose study to
      determine a maximum tolerated dose
    

Eligibility criteria:

        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.