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

Epilepsy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00987558
• Other study ID #: BIA-2093-124
• Status: Completed
• Phase: Phase 1
• First received: September 30, 2009
• Last updated: January 12, 2015
• Start date: June 2009
• Est. completion date: August 2009

Study information

• Verified date: January 2015
• Source: Bial - Portela C S.A.
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: August 2009
• Est. primary completion date: August 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 45 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Epilepsy

Intervention

Drug:
• Eslicarbazepine acetate

• Simvastatin

Locations

Country	Name	City	State
France	Biotrial, 7-9 rue Jean-Louis Bertrand	Rennes

Sponsors (1)

Lead Sponsor	Collaborator
Bial - Portela C S.A.

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Simvastatin Cmax (Maximum Plasma Concentration)	Simvastatin (Reference) ESL + Simvastatin (Test)	Day 1 and Day 14	No
Primary	Simvastatin Tmax (Time of Occurrence of Cmax)	Simvastatin (Reference) ESL + Simvastatin (Test)	Day 1 and Day 14	No
Primary	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	No
Primary	Simvastatin AUC0-8 (AUC From Time Zero to Infinity)	Simvastatin (Reference) ESL + Simvastatin (Test)	Day 1 and Day 14	No