Effect of Repeated Administration of Eslicarbazepine Acetate on the Pharmacokinetics of Simvastatin in Healthy Subjects

The primary objective was to investigate whether multiple-dose administration of ESL 800 mg once daily affects the pharmacokinetics of simvastatin, a substrate of CYP34A.

Study Overview

• Status: Completed
• Conditions: Epilepsy
• Intervention / Treatment: Drug: Simvastatin; Drug: Eslicarbazepine acetate

Detailed Description

This was a single centre, two-way crossover, randomised, open-label study in 24 healthy volunteers. The volunteers will receive an oral single-dose of simvastatin 80 mg on two occasions - once administered alone and once after treatment with an oral once-daily dose of 800 mg of ESL for 14 days -, separated by a washout period of 3 weeks or more

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Rennes, France, F-35000
    • Biotrial, 7-9 rue Jean-Louis Bertrand

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and female subjects aged 18 to 45 years, inclusive
• Body mass index (BMI) between 18 and 30 kg/m2, inclusive
• Healthy as determined by pre-study medical history, physical examination, vital signs, and 12-lead ECG; negative tests for HBsAg, anti-HCVAb and HIV-1 and HIV-2 Ab at screening; clinical laboratory test results clinically acceptable at screening and admission to each treatment period;
• Negative screen for alcohol and drugs of abuse at screening and admission to each treatment period
• Non-smokers or ex-smokers
• Able and willing to give written informed consent;
• If female, not of childbearing potential by reason of surgery or, if of childbearing potential, she uses one of the following methods of contraception: double barrier method: 1 male barrier method [male condom] plus 1 female barrier method (diaphragm, spermicide, or intrauterine device);
• If female, has a negative urine pregnancy test at screening and admission to each treatment period.

Exclusion Criteria:

• Clinically relevant history or presence of respiratory, gastrointestinal, renal, hepatic, haematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, endocrine, connective tissue diseases or disorders
• Clinically relevant surgical history;
• History of relevant atopy or any drug hypersensitivity (including known hypersensitivity to ESL or other carboxamide derivatives, simvastatin or other statins or any of its excipients
• History of fibromyalgia, myopathy, rhabdomyolysis or unexplained muscle pain
• Second or third-degree atrioventricular blockade not corrected with a pacemaker or any other clinically significant abnormality in the 12-lead electrocardiogram (ECG) as determined by the investigator
• History of alcoholism or drug abuse
• Consume more than 14 units of alcohol a week
• Significant infection or known inflammatory process on screening or admission to each treatment period
• Acute gastrointestinal symptoms (e.g., nausea, vomiting, diarrhoea, heartburn) at the time of screening or admission to each treatment period
• Use of medicines within two weeks of admission to first period that may affect the safety or other study assessments, in the investigator's opinion
• Have donated or received any blood or blood products within the 3 months prior to screening
• Vegetarians, vegans or have other medical dietary restrictions
• Cannot communicate reliably with the investigator
• Unlikely to co-operate with the requirements of the study
• Unwilling or unable to give written informed consent
• If female, is pregnant or breast-feeding
• If female, is of childbearing potential and does not use an approved effective contraceptive method (double-barrier method: 1 male barrier method [male condom] plus 1 female barrier method (diaphragm, spermicide, or intra-uterine device) or uses hormonal contraceptives
• Have received an investigational drug within 3 months of screening or is currently participating in another study

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Sequence A; Simvastatin 80mg treatment period followed by Simvastatin 80 mg + eslicarbazepine acetate 800 mg treatment period	Drug: Simvastatin; Other Names: Zocor; Drug: Eslicarbazepine acetate; Other Names: Zebinix
Experimental: Treatment Sequence B; Simvastatin 80mg + eslicarbazepine acetate 800 mg treatment period followed by Simvastatin 80 mg treatment period	Drug: Simvastatin; Other Names: Zocor; Drug: Eslicarbazepine acetate; Other Names: Zebinix

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Simvastatin Cmax (Maximum Plasma Concentration)	Simvastatin (Reference) ESL + Simvastatin (Test)	Day 1 and Day 14
Simvastatin Tmax (Time of Occurrence of Cmax)	Simvastatin (Reference) ESL + Simvastatin (Test)	Day 1 and Day 14
Simvastatin AUC0-t	AUC0-t - area under the plasma concentration versus time curve (AUC) from time zero to the last sampling time at which concentrations were at or above the limit of quantification Simvastatin (Reference) ESL + Simvastatin (Test)	Day 1 and Day 14
Simvastatin AUC0-∞ (AUC From Time Zero to Infinity)	Simvastatin (Reference) ESL + Simvastatin (Test)	Day 1 and Day 14

Collaborators and Investigators

• Sponsor: Bial - Portela C S.A.
• Investigators: Principal Investigator: Marie Claude Homery, MD, Biotrial, 7-9, rue Jean-Louis Bertrand, F-35000 Rennes, France

Study record dates

Study Major Dates

• Study Start: June 1, 2009
• Primary Completion (Actual): August 1, 2009
• Study Completion (Actual): August 1, 2009

Study Registration Dates

• First Submitted: September 30, 2009
• First Submitted That Met QC Criteria: September 30, 2009
• First Posted (Estimate): October 1, 2009

Study Record Updates

• Last Update Posted (Estimate): January 13, 2015
• Last Update Submitted That Met QC Criteria: January 12, 2015
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Keywords: simvastatin; Eslicarbazepine acetate
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Membrane Transport Modulators; Anticonvulsants; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Simvastatin; Eslicarbazepine acetate
• Other Study ID Numbers: BIA-2093-124