EXTENT: EXtended Tolerability and Efficacy of a Novel Formulation of Oxcarbazepine in a Trial in Partial Epilepsy

Condition(s) targeted: Partial Epilepsy

Intervention: modified release formulation of oxcarbazepine (OXC MR) (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: Desitin Arzneimittel GmbH

Official(s) and/or principal investigator(s):
Christian E. Elger, Prof. MD, Principal Investigator, Affiliation: Klinik für Epileptologie, Universität Bonn, Bonn, Germany
Martina Wangemann, Dr., Study Director, Affiliation: Desitin Arzneimittel GmbH

Overall contact:
Dr. Martina Wangemann Wangemann, PhD, Phone: +49 40 59101, Ext: 396, Email: Wangemann@Desitin.de

This study is intended to investigate the safety and efficacy of a novel formulation of oxcarbazepine that is released more slowly than the current formulation. The study medication will be used as a treatment against partial epilepsy.

Official title: Safety and Efficacy of a Novel Modified Release Formulation of Oxcarbazepine (OXC MR) vs an Immediate Release Oxcarbazepine (OXC IR) Product in Patients With Partial Epilepsy

Study design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: Maintenance dosage where dose up-titration has to be discontinued due to AEs

Secondary outcome:

Number of seizures during the trial

OXC and MHD plasma levels obtained from 6 patients per centre

Adverse event profile Plus (AEP) questionnaire-score

EpiTrack

Systolic and diastolic blood pressure in supine and standing position

Pulse rate

ECG

Serum chemistry

Coagulation

Hematology

Urinalysis

Detailed description: This is a multi-centre (5 centres), randomized, open-label, flexible-titration, controlled, parallel-group study to investigate the safety and efficacy of a novel modified release formulation of oxcarbazepine (OXC MR) compared to an immediate release oxcarbazepine (OXC IR) product in patients with partial epilepsy. Adult patients of both gender, aged at least 18 years with refractory partial epilepsy, with or without secondary generalisation receiving a stable background treatment with daily dosages of exactly 900 or 1200 mg Oxcarbazepine will be enrolled. Concomitant medication consisting of maximal 2 additional AEDs (vagus nerve stimulator included) is allowed and must be kept stable throughout the study. Patients, who agree to participate, will first sign and date the informed consent and undergo an evaluation at screening visit to determine eligibility. Those patients who qualify will be enrolled in the study, assigned a patient ID, and will enter the 4-week baseline period. Each patient will receive a seizure diary to record the number of seizures during the baseline period. For Visit 1 the patient will return to the clinic and complete all baseline procedures. Patients who have met the entry criteria will be randomised. The two treatment groups consist of 50 patients each, one group to be treated with OXC MR b. i.d. and the other to be treated with OXC IR b. i.d. in a 1: 1 randomization. Following assignment to one of both treatment groups the patient will enter the dose-titration phase. From Visit 1 (Study Day 1) a total daily dose of 1200 mg /1500 mg oxcarbazepine will be given to the randomised patients. From Day 6 the dosage will be titrated to a maximum total daily dose of 2700 mg in steps of 300 mg every 6th day. Patients who experienced intolerable adverse events could reduce their daily dose by 150 mg on the 2nd day of up-titration for the remainder of the treatment period. In case the reduced dosage will also not be tolerated, in a second step the dosage can be reduced by further 150 mg OXC. The maximal tolerated dose achieved on up-titration will be maintained up to the final visit (Study Day 26).

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Female and male patients with minimal age of 18 years on the date of the first study

visit.

- Stable treatment with Oxcarbazepine treatment, dosage: exactly 900 mg or exactly 1200

mg for at least 1 month prior to screening.

- >= 2 partial onset seizures with or without secondary generalisation refractory to

existing AED therapy within the baseline period.

- Weight between >= 50 kg and < 100 kg.

- for females with child-bearing potential: negative pregnancy rest and highly

effective form of birth control (females using hormonal contraceptives should use a different or additional means of birth control, e. g. IUD, abstinence, vasectomized partner, double barriere methods with or without oral contraceptives)

- Stable regimen of <= 2 concomitant AEDs (vagus nerve stimulator included) during the

baseline period; lamotrigine dose may be adjusted at baseline.

- Ethnic origin: Caucasian.

- Subjects capable of complying with the study stipulations.

- Patients who have provided written informed consent to participate in this study.

Exclusion Criteria:

- Epilepsy secondary to progressive metabolic disease, malignant neoplasm, substance

abuse, or active infection.

- Status epilepticus at any time during the baseline period.

- Lennox-Gastaut syndrome.

- Generalized epilepsy as primary diagnosis.

- Severe cardiac, pulmonary, haematological, hepatic, renal or neoplastic pathology.

- Acute medical conditions and/or conditions that could interfere with the absorption,

metabolism or excretion of oxcarbazepine.

- History of clinically relevant psychiatric illness and/or drug abuse, drug addiction

or alcoholism within the last 2 years.

- Treatment with psychotropic drugs, anticholinergic drugs, anti-parkinson medication,

a1-antagonists, a2-antagonists, carbamazepine, topiramate, felbamate, vigabatrin.

- Intake of sodium lowering medication, e. g. diuretics and non-steroidal

anti-inflammatory drugs.

- Hypersensitivity towards oxcarbazepine or chemically related drugs.

- Low sodium serum levels (<= 130 mmol/L).

- Pregnancy or breast feeding.

- Participation in drug trials during 3 months preceding the study.

Dr. Martina Wangemann Wangemann, PhD, Phone: +49 40 59101, Ext: 396, Email: Wangemann@Desitin.de

Klinik für Epileptologie, Universität Bonn, Bonn 53127, Germany; Recruiting
Christian E. Elger, Prof. MD, Principal Investigator

Starting date: October 2006
Ending date: December 2009
Last updated: January 12, 2009