A Study of the Pharmacokinetics (PK) and Safety of IV Carbamazepine Relative to Oral Carbamazepine in Adults With Epilepsy

April 22, 2010 updated by: Lundbeck LLC

A Sequential, Open-Label Study of the Pharmacokinetics and Safety of Intravenous Carbamazepine Relative to Oral Carbamazepine in Adult Patients With Epilepsy

The purpose of this study is to assess the safety, tolerability and steady-state pharmacokinetics of intravenous (IV) Carbamazepine (CBZ) infusions relative to orally administered CBZ in adult patients with epilepsy.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This phase 1, multicenter, sequential, open-label study was designed to assess the safety, tolerability and pharmacokinetics of IV CBZ relative to orally administered CBZ in adult subjects with epilepsy. The study design used an increasing dose/treatment escalation cohort paradigm wherein subjects were enrolled in a cohort based on their total daily dose (TDD) of oral CBZ and their calculated creatinine clearance (CLcr; calculated by the Cockroft-Gault equation) on Day -28. The purpose of the increasing dose/treatment escalation cohort design was to provide a means for the independent data monitoring committee (IDMC) to assess safety prior to enrolling in subsequent cohorts; data were summarized by infusion time, renal function and dose. The initial subjects enrolled had normal renal function (CLcr >= 80 mL/min) and were stable on oral dosing of CBZ from 400 mg/day to 800 mg/day. Subsequent Dosing Cohorts enrolled subjects on higher doses of oral CBZ and allowed subjects with some renal impairment to be enrolled.

Study Type

Interventional

Enrollment (Actual)

98

Phase

  • Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patient must be diagnosed with any of the approved epilepsy indications for CBZ that include: Partial seizures with complex symptomatology (psychomotor, temporal lobe); Generalized tonic clonic seizures (grand mal); Mixed seizure patterns that include one of the above; Other partial or generalized seizures.
  • Patient must be receiving a stable dose of oral CBZ (tablet or capsule formulation) for a minimum of 14 days prior to Day -28.
  • Patient must be receiving a constant dose of all other concomitant medications / device (including AEDs, Vagal Nerve Stimulator (VNS), OTC medications, and herbal supplements) that may not interfere with the metabolism of CBZ for a minimum of 14 days prior to Day -28. No change in baseline AEDs are expected during the treatment period.
  • The patient must be able to comply with maintaining an accurate epilepsy medication dosing diary and seizure diary.
  • If female: Patient is not of childbearing potential.
  • If childbearing potential: Must have a negative serum pregnancy test at Day -28 and a negative serum pregnancy test on Day -1; Must comply with a method of birth control acceptable to the investigator (with the exception of hormone based contraceptives which are contraindicated with the use of CBZ).

Exclusion Criteria:

  • Patient is taking a daily oral dose of CBZ greater than 2000 mg per day.
  • Patient is being treated with hormone based therapy for birth control.
  • Patient has a QTc interval value that is greater than 450 msec.
  • Patient has a screening ALT, AST or bilirubin > 3 times the upper limit of normal.
  • Patients with CLCR < 30 mL/min or with a renal disorder (i.e. nephrotic syndrome, patients on hemodialysis or peritoneal dialysis or being considered for peritoneal or hemodialysis).
  • Patient is receiving oral CBZ for absence seizures.
  • Patient has had an episode of status epilepticus within 30 days of screening.
  • Patient has a history of severe or serious adverse reactions to CBZ (e.g. aplastic anemia, agranulocytosis).
  • Patient has been diagnosed with narrow angle glaucoma.
  • Patient weighs less than 50 kg.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
To assess the safety, tolerability and pharmacokinetics of IV CBZ as a 30- and 15-minute infusion relative to orally administered CBZ in adult patients with epilepsy.
Time Frame: 31 days
31 days
To compare the steady-state pharmacokinetics of intravenously administered CBZ (Day 7) relative to orally administered CBZ (Day 0).
Time Frame: Day 7
Day 7

Secondary Outcome Measures

Outcome Measure
Time Frame
To assess the safety, tolerability and pharmacokinetics of IV CBZ when administered over a 2-5-minute infusion in a subset of patients.
Time Frame: 31 days
31 days
To assess the safety, tolerability and pharmacokinetics of IV CBZ in patients with mild or moderate renal impairment.
Time Frame: 31 days
31 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Lundbeck LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2007

Primary Completion (Actual)

March 1, 2009

Study Completion (Actual)

April 1, 2009

Study Registration Dates

First Submitted

March 1, 2010

First Submitted That Met QC Criteria

March 2, 2010

First Posted (Estimate)

March 3, 2010

Study Record Updates

Last Update Posted (Estimate)

April 23, 2010

Last Update Submitted That Met QC Criteria

April 22, 2010

Last Verified

April 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 13103A
  • OV-1015 (Other Identifier: Former study ID)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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