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

This study has been completed.
Sponsor:
Collaborators:
Ligand Pharmaceuticals
ICON Clinical Research
Quintiles
Information provided by (Responsible Party):
Lundbeck LLC
ClinicalTrials.gov Identifier:
NCT01128959
First received: May 21, 2010
Last updated: April 11, 2014
Last verified: April 2014
  Purpose

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


Condition Intervention Phase
Epilepsy
Drug: Intravenous Carbamazepine (IV CBZ)
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Open-Label Study to Assess the Safety and Tolerability of Intravenous Carbamazepine as Short-Term Replacement of Oral Carbamazepine in Adult Patients With Epilepsy

Resource links provided by NLM:


Further study details as provided by Lundbeck LLC:

Primary Outcome Measures:
  • The primary objective to assess the safety and tolerability of IV CBZ administered as multiple 15 minute infusions to adult patients with epilepsy on stable higher doses of oral CBZ includes adverse events, laboratory test results, and ECG parameters [ Time Frame: 13 infusions administered across 4 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • For the secondary objective to assess biomarkers for renal effect of IV CBZ, the variables of interest include the analytes collected in the 24-hour urine collection relative to the creatinine volume excreted [ Time Frame: Measures will be taken across all days of IV infusion (4 days) ] [ Designated as safety issue: Yes ]

Enrollment: 108
Study Start Date: June 2010
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

Detailed Description:

This is 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 will include a 28 day Lead-in Period, a Confinement Period (up to 7 days and 6 nights) and a 28 day Follow-up Period.

Patients will begin 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 will begin the 24hr urine collection for evaluation of urinary biomarkers. All patients will temporarily discontinue 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01128959

  Show 29 Study Locations
Sponsors and Collaborators
Lundbeck LLC
Ligand Pharmaceuticals
ICON Clinical Research
Quintiles
Investigators
Study Director: Email contact via H. Lundbeck A/S LundbeckClinicalTrials@lundbeck.com
  More Information

No publications provided

Responsible Party: Lundbeck LLC
ClinicalTrials.gov Identifier: NCT01128959     History of Changes
Other Study ID Numbers: 13181A
Study First Received: May 21, 2010
Last Updated: April 11, 2014
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
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Antimanic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Psychotropic Drugs
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on October 19, 2014