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

Phase 1

Completed

• Conditions: Epilepsy
• Interventions: Drug: Eslicarbazepine acetate; Drug: Simvastatin

• Registration Number: NCT00987558
• Lead Sponsor: Bial - Portela C S.A.

Brief Summary

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.

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 Timeline

• Study Start: 2009-06
• Primary Completion: 2009-08
• Study Completion: 2009-08
• Study First Submitted: 2009-09-30
• Study First Submitted QC: 2009-09-30
• Study First Posted: 2009-10-01
• Results First Submitted: 2014-12-03
• Status Verified: 2015-01
• Results First Submitted QC: 2015-01-12
• Last Update Submitted: 2015-01-12
• Results First Posted: 2015-01-13
• Last Update Posted: 2015-01-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Treatment Sequence A	Eslicarbazepine acetate	Simvastatin 80mg treatment period followed by Simvastatin 80 mg + eslicarbazepine acetate 800 mg treatment period
Treatment Sequence B	Simvastatin	Simvastatin 80mg + eslicarbazepine acetate 800 mg treatment period followed by Simvastatin 80 mg treatment period
Treatment Sequence A	Simvastatin	Simvastatin 80mg treatment period followed by Simvastatin 80 mg + eslicarbazepine acetate 800 mg treatment period
Treatment Sequence B	Eslicarbazepine acetate	Simvastatin 80mg + eslicarbazepine acetate 800 mg treatment period followed by Simvastatin 80 mg treatment period

Primary Outcome Measures

Name	Time	Method
Simvastatin AUC0-t	Day 1 and Day 14	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)
Simvastatin Tmax (Time of Occurrence of Cmax)	Day 1 and Day 14	Simvastatin (Reference) ESL + Simvastatin (Test)
Simvastatin Cmax (Maximum Plasma Concentration)	Day 1 and Day 14	Simvastatin (Reference) ESL + Simvastatin (Test)
Simvastatin AUC0-∞ (AUC From Time Zero to Infinity)	Day 1 and Day 14	Simvastatin (Reference) ESL + Simvastatin (Test)

Trial Locations

Locations (1)

Biotrial, 7-9 rue Jean-Louis Bertrand; 🇫🇷 Rennes, France