Study to Assess the Safety and Tolerability of Intravenous Carbamazepine in Adults With Epilepsy

Open-Label Study to Assess the Safety and Tolerability of Intravenous Carbamazepine as Short-Term Replacement of Oral Carbamazepine in Adult Patients With Epilepsy

The purpose of this study is to assess the safety and tolerability of intravenous (IV) carbamazepine (CBZ) administered as multiple 15 minute infusions and a single 5 minute infusion to adult patients with epilepsy on stable higher doses of oral CBZ.

Study Overview

• Status: Completed
• Conditions: Epilepsy
• Intervention / Treatment: Drug: Intravenous Carbamazepine (IV CBZ)

Detailed Description

This was a phase III, multicenter, open-label study designed to assess the safety and tolerability of intravenously administered CBZ in adult patients with epilepsy. This study included a 28 day Lead-in Period, a Confinement Period (up to 7 days and 6 nights) and a 28 day Follow-up Period.

Patients began confinement on Day -1 of the trial, continuing to take their oral CBZ as prescribed by the investigator. On the morning of Day 0, Day 4, and Day 17, patients began the 24hr urine collection for evaluation of urinary biomarkers. All patients temporarily discontinued their prescribed oral CBZ and begin IV CBZ administration on the morning of Day 1, continuing administrations every 6 hours (Q6h) through the morning of Day 4.

• Study Type: Interventional
• Enrollment (Actual): 108
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic Arizona
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Clinical Trials Incorporated
  • California
    • Torrance, California, United States, 90502
      • Collaborative Neuroscience Network, Inc.
  • Colorado
    • Denver, Colorado, United States, 80204
      • Denver Health and Hospital Authority
  • Florida
    • Tampa, Florida, United States, 33606
      • University of South Florida
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University of Illinois at Chicago
    • Springfield, Illinois, United States, 62702
      • Southern Illinois University School of Medicine
    • Winfield, Illinois, United States, 60190
      • Central DuPage Hospital
  • Kansas
    • Wichita, Kansas, United States, 67214
      • Via Christi Epilepsy Center
  • Louisiana
    • Houma, Louisiana, United States, 70363
      • Leonard J. Chabert Medical Center
    • New Orleans, Louisiana, United States, 70114
      • Louisiana Research Associates
    • New Orleans, Louisiana, United States, 70115
      • Ochsner Clinic Foundation
  • Maryland
    • Bethesda, Maryland, United States, 20815
      • Mid-Atlantic Epilepsy and Sleep Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
  • Minnesota
    • Saint Paul, Minnesota, United States, 55114
      • University of Minnesota & Prism Research
  • Missouri
    • Chesterfield, Missouri, United States, 63017
      • The Comprehensive Epilepsy Care Center for Children and Adults
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medicical Center
    • New York, New York, United States, 10016
      • Langone Medical Center NYU Comprehensive Epilepsy Center
    • New York, New York, United States, 10032
      • Columbia University Medical Center: Dept of Neurology
    • Rochester, New York, United States, 14642
      • University of Rochester
    • Syracuse, New York, United States, 13210
      • SUNY Upstate Medical University
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University Health Systems
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Texas
    • Dallas, Texas, United States, 75230
      • Neurological Clinic of Texas, P.A.
    • Temple, Texas, United States, 76508
      • Scott & White Memorial Hospital
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia
    • Richmond, Virginia, United States, 23298-0599
      • VCU Medical Center

Participation Criteria

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:

1. The patient or legal representative must be able to read, understand, sign and date the IRB approved Informed Consent Form and HIPAA Authorization prior to study participation.
2. The patient is a man or a non-pregnant woman who is at least 18 years of age.

3. If a woman:

   • Patient is either not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile (bilateral tubal ligation, bilateral oophorectomay or hysterectomy), or if childbearing potential, must comply with a method of birth control acceptable to the investigator during the study, for at least 28 days prior to Day 1 and for 28 days following completion of the study.
   • Patient is not breastfeeding.
   • Patient of childbearing potential must have a negative serum pregnancy test at Day -28 and a negative urine pregnancy test or serum pregnancy test at Day -1.

4. The patient is diagnosed with any of the approved epilepsy indications for CBZ:

   • Partial seizures with complex symptomatology (psychomotor, temporal lobe)
   • Generalised tonic clonic seizures (GTCS) (grand mal): myoclonic, clonic, tonic, tonic-clonic, atonic
   • Mixed seizure patterns that include the above, or other partial or generalised seizures (except absence seizures - please see exclusion point number 12)
5. The patient is receiving a stable dose of oral CBZ (tablet or capsule formulation) of 1200 mg/day to 2000 mg/day, for a minimum of 14 days prior to Day -28.
6. The patient is receiving a constant dose of all other concomitant medications used for chronic conditions, (including OTC medications and herbal supplements) for a minimum of 28 days prior to Day 1.
7. The patient is not expected to have any change in his/her baseline AED treatment during the treatment period.
8. The patient is able to comply with maintaining an accurate Seizure and antiepileptic drug diary.
9. The patient is able to comply with all study procedures including complying with protocol determined dosing intervals, confinement at the investigative site for up to 6 nights and 7 days, and agrees to participate in the entire study.

Exclusion Criteria:

1. The patient has a known hypersensitivity to CBZ, Captisol, or to any of the tricyclic compounds, such as amitriptyline, trimipramine, imipramine; oxacarbazepine, phenytoin, or their analogues or metabolites.
2. The patient has a history of previous bone marrow depression.
3. The patient has a history of intolerance to IV administration of medication.
4. The patient is pregnant or lactating.
5. The patient is being treated with a monoamine oxidase (MAO) inhibitor.
6. The patient is using oral, intramuscular, or any other hormone delivery method as their primary form of birth control.
7. The patient has an ECG with corrected QT interval by Fridericia's correction formula (QTcF) greater than 450 msec at Screening or Day -1.
8. The patient has a screening ALT, AST or bilirubin >=3 times the upper limit of normal.
9. The patient has an estimated ClCR (based of Cockcroft-Gault) of <50 ml/min.
10. The patient has had a clinically significant illness/infection or has had any surgical procedure within 30 days prior to Screening.
11. The patient has a significant history of cardiac, renal, neurologic (other than epilepsy), psychiatric, oncologic, endocrinologic, metabolic, or hepatic disease, which would adversely affect their participation in this study.
12. The patient is receiving oral CBZ for absence seizures.
13. The patient has had an episode of status epilepticus within 4 weeks of Screening.
14. The patient has a history of severe or serious adverse reactions to CBZ (for example, aplastic anemia, agranulocytosis, SJS.
15. The patient has taken or used any investigational drug or device in the 30 days prior to Screening.
16. The patient has previously been administered IV CBZ in a previous clinical trial (for example OV-1015).
17. The patient has a urine toxicology screen positive for phencyclidine, benzodiazepines (unless due to the patient's concomitant AEDs), cannabinoids, cocaine, amphetamines, opiates, barbiturates (unless due to the patient's concomitant AEDs), or alcohol at Screening or Day -1.
18. The patient has had a diagnosis of drug or alcohol abuse within the past year prior to Screening.
19. The patient has had significant blood loss (>500 mL) or donation within 14 days of Screening.
20. The patient has a history of poor oral CBZ compliance.
21. The patient is participating in a weight loss or nicotine cessation program.
22. The patient has a history of increased intraocular pressure or is on medication for glaucoma.
23. The patient is considered by the investigator to be an unsuitable candidate for the study, which may include an increase in the frequency, severity and duration of seizures during the Pre-Treatment Period (Days -28-0).
24. The patient has previously participated in this study.
25. The patient is a member of the site personnel or their immediate families.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intravenous Carbamazepine (IV CBZ)	Drug: Intravenous Carbamazepine (IV CBZ); 10 mg/mL of IV CBZ dissolved in 250 mg/mL of Captisol® (sulfobutylether-beta-cyclodextrin) dosed at 70% of the patient's daily maintenance dose of oral CBZ administered after suitable dilution with D5W by IV infusion every 6 hours.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Adverse Events	Baseline to after last iv dose on day 4

Collaborators and Investigators

• Sponsor: Lundbeck LLC
• Collaborators: Quintiles, Inc.; ICON Clinical Research; Ligand Pharmaceuticals

Publications and helpful links

General Publications

• Lee D, Kalu U, Halford JJ, Biton V, Cloyd J, Klein P, Bekersky I, Peng G, Dheerendra S, Tolbert D. Intravenous carbamazepine as short-term replacement therapy for oral carbamazepine in adults with epilepsy: Pooled tolerability results from two open-label trials. Epilepsia. 2015 Jun;56(6):906-14. doi: 10.1111/epi.12991. Epub 2015 Apr 25.

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (Actual): January 1, 2013
• Study Completion (Actual): January 1, 2013

Study Registration Dates

• First Submitted: May 21, 2010
• First Submitted That Met QC Criteria: May 21, 2010
• First Posted (Estimate): May 24, 2010

Study Record Updates

• Last Update Posted (Actual): January 16, 2018
• Last Update Submitted That Met QC Criteria: December 14, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Keywords: Epilepsy; Intravenous Carbamazepine; Oral Carbamazepine
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Anticonvulsants; Sodium Channel Blockers; Antimanic Agents; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Carbamazepine
• Other Study ID Numbers: 13181A