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

NCT ID: NCT01128959

Last Updated: 2018-01-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 108 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-06-30
• Study Completion Date: 2013-01-31

Brief Summary

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.

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.

Conditions

Epilepsy

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Intravenous Carbamazepine (IV CBZ)

Group Type: EXPERIMENTAL

Intravenous Carbamazepine (IV CBZ)

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ligand Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

ICON Clinical Research

INDUSTRY

Sponsor Role: collaborator

Quintiles, Inc.

INDUSTRY

Sponsor Role: collaborator

Lundbeck LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Email contact via H. Lundbeck A/S

Role: STUDY_DIRECTOR

LundbeckClinicalTrials@lundbeck.com

Locations

Mayo Clinic Arizona

Phoenix, Arizona, United States

Clinical Trials Incorporated

Little Rock, Arkansas, United States

Collaborative Neuroscience Network, Inc.

Torrance, California, United States

Denver Health and Hospital Authority

Denver, Colorado, United States

University of South Florida

Tampa, Florida, United States

University of Illinois at Chicago

Chicago, Illinois, United States

Southern illinois University School of Medicine

Springfield, Illinois, United States

Central DuPage Hospital

Winfield, Illinois, United States

Via Christi Epilepsy Center

Wichita, Kansas, United States

Leonard J. Chabert Medical Center

Houma, Louisiana, United States

Louisiana Research Associates

New Orleans, Louisiana, United States

Ochsner Clinic Foundation

New Orleans, Louisiana, United States

Mid-Atlantic Epilepsy and Sleep Center

Bethesda, Maryland, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

University of Minnesota & Prism Research

Saint Paul, Minnesota, United States

The Comprehensive Epilepsy Care Center for Children and Adults

Chesterfield, Missouri, United States

Langone Medical Center NYU Comprehensive Epilepsy Center

New York, New York, United States

Columbia University Medical Center: Dept of Neurology

New York, New York, United States

University of Rochester

Rochester, New York, United States

SUNY Upstate Medical University

Syracuse, New York, United States

Montefiore Medicical Center

The Bronx, New York, United States

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

Cleveland Clinic

Cleveland, Ohio, United States

Temple University Health systems

Philadelphia, Pennsylvania, United States

Medical University of South Carolina

Charleston, South Carolina, United States

Neurological Clinic of Texas, P.A.

Dallas, Texas, United States

Scott & White Memorial Hospital

Temple, Texas, United States

University of Virginia

Charlottesville, Virginia, United States

VCU Medical Center

Richmond, Virginia, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 25912051 (View on PubMed)

Other Identifiers

13181A

Identifier Type: -

Identifier Source: org_study_id