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

Purpose

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.

Condition	Intervention	Phase
Epilepsy	Drug: Intravenous Carbamazepine	Phase 1

Study Type:	Interventional
Study Design:	Endpoint Classification: Pharmacokinetics Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Sequential, Open-Label Study of the Pharmacokinetics and Safety of Intravenous Carbamazepine Relative to Oral Carbamazepine in Adult Patients With Epilepsy

Resource links provided by NLM:

Genetics Home Reference related topics: pyridoxal 5'-phosphate-dependent epilepsy

MedlinePlus related topics: Epilepsy

Drug Information available for: Carbamazepine

U.S. FDA Resources

Further study details as provided by Lundbeck LLC:

Primary Outcome Measures:

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 ] [ Designated as safety issue: Yes ]
To compare the steady-state pharmacokinetics of intravenously administered CBZ (Day 7) relative to orally administered CBZ (Day 0). [ Time Frame: Day 7 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

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 ] [ Designated as safety issue: Yes ]
To assess the safety, tolerability and pharmacokinetics of IV CBZ in patients with mild or moderate renal impairment. [ Time Frame: 31 days ] [ Designated as safety issue: Yes ]

Enrollment:	98
Study Start Date:	April 2007
Study Completion Date:	April 2009
Primary Completion Date:	March 2009 (Final data collection date for primary outcome measure)

Intervention Details:

10 mg/mL of intravenous Carbamazepine (CBZ) dissolved in 250 mg/mL of Captisol® (cyclodextrin) dosed at 70% of the patient's daily maintenance dose of oral CBZ administered after suitable dilution with D5W by intravenous infusion every 6 hours.

Other Name: IV CBZ

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01079351

Sponsors and Collaborators

Lundbeck LLC

Investigators

Study Director:

Email contact via H. Lundbeck A/S

LundbeckClinicalTrials@lundbeck.com

More Information

No publications provided

Responsible Party:	Lundbeck Inc.
ClinicalTrials.gov Identifier:	NCT01079351 History of Changes
Other Study ID Numbers:	13103A, OV-1015
Study First Received:	March 1, 2010
Last Updated:	April 22, 2010
Health Authority:	United States: Food and Drug Administration

Keywords provided by Lundbeck LLC:

Epilepsy
Intravenous Carbamazepine
Oral Carbamazepine

Additional relevant MeSH terms:

Epilepsy
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Carbamazepine
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents

Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Anticonvulsants
Antimanic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs

ClinicalTrials.gov processed this record on May 22, 2013