A Sequential Multiple Ascending Dose Study of the Safety and Pharmacokinetics of Eslicarbazepine Acetate in Adult Healthy Volunteers

• Status: Completed
• Trial end date: 2007-02-01
• Target enrollment: 0
• Participant gender: All

Summary

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

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Bial - Portela C S.A.
• Treatments: Eslicarbazepine acetate

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.