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Characterization of Epilepsy Patients BEEP 2b (BEEP2b)

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ClinicalTrials.gov Identifier: NCT02707965
Recruitment Status : Completed
First Posted : March 14, 2016
Last Update Posted : October 23, 2018
Sponsor:
Collaborator:
University of Maryland
Information provided by (Responsible Party):
Food and Drug Administration (FDA)

Tracking Information
First Submitted Date  ICMJE February 26, 2016
First Posted Date  ICMJE March 14, 2016
Last Update Posted Date October 23, 2018
Actual Study Start Date  ICMJE June 8, 2017
Actual Primary Completion Date August 2, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 8, 2016)
  • AUC0-last_ss [ Time Frame: For all study drugs, time points are: predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, and 6 hr postdose. For twice-a-day regimen, additional points are:8, 10, and 12 hr postdose. For once-a-day drugs, additional times are:8, 10, 12, 16, and 24 hr postdose. ]
    area under the drug plasma curve; compute over the entire dosing interval, which is either 6, 8, or 12 hr in duration depending on the individual patient's prescription
  • Cmax_ss [ Time Frame: For all study drugs, time points are: predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, and 6 hr postdose. For twice-a-day regimen, additional points are:8, 10, and 12 hr postdose. For once-a-day drugs, additional times are:8, 10, 12, 16, and 24 hr postdose. ]
    maximum drug plasma concentration; determined from the entire dosing interval, which is either 6, 8, or 12 hr in duration depending on the individual patient's prescription
  • Cmin_ss [ Time Frame: For all study drugs, time points are: predose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, and 6 hr postdose. For twice-a-day regimen, additional points are:8, 10, and 12 hr postdose. For once-a-day drugs, additional times are:8, 10, 12, 16, and 24 hr postdose. ]
    minimum drug plasma concentration; determined from the entire dosing interval, which is either 6, 8, or 12 hr in duration depending on the individual patient's prescription
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02707965 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 8, 2016)
  • Number of seizures [ Time Frame: Through the approximately 2 week period when the treatment is given. ]
    summed for each brand and generic from when taking brand and generic, respectively
  • Number of adverse events [ Time Frame: Through the approximately 2 week period when the treatment is given. ]
    summed for each brand and generic from when taking brand and generic, respectively
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Characterization of Epilepsy Patients BEEP 2b
Official Title  ICMJE Characterization of Epilepsy Patients At-risk for Adverse Outcomes Related to Switching Antiepileptic Drug Products: BEEP 2b Study
Brief Summary Some epilepsy patients are described as GB when they have worsened seizures or side effects related to switching between brand name and generic, or between generic antiepileptic drug (AED) products. In concert with Aim 1 (protocol BEEP2a), this study will uncover possible reasons for patient problems with the drug switching. Factors that will be studied in GB epilepsy patients include physiologic, psychological, and genetic factors, including in this protocol whether brand and generic AEDs are pharmacokinetically similar in GB individuals.
Detailed Description

This pilot study is exploratory research to characterize the "generic brittle" (GB) patient and to identify major causes for generic brittleness in epilepsy patients who are sensitive to antiepileptic drug (AED) formulation changes.

The primary aim of this BEEP2b study is to perform individual pharmacokinetic (PK) similarity testing of brand and generic AEDs in "probably GB" patients (N=12),who were selected on the basis of having GB-defining factors from the BEEP2a study, in order to confirm whether these factors are predictive of a generic brittle response to product switching. The study design involves a randomized, double-blind, multiple-dose, complete four-way replicate crossover design in which one brand and one generic will be compared in each patient from the patient's own AED regimen. Associated adverse events (i.e. seizures and side effects) will also be assessed. Bioequivalence (BE) will not be assessed. Rather, about nine AEDs are expected to be collectively evaluated. Generic brittleness anticipates that, for individual subjects, brand and generic may be the same or different, depending upon the underlying basis for generic brittleness. This exploratory research is focused on understanding individual patient attributes that contribute to GB, and is not focused on either product development or comparison of specific products.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Epilepsy
Intervention  ICMJE
  • Drug: Oxcarbmazepine (brand name vs generic drugs)
    This is a cross-over replicate study with 2 sequences (arms) comparing brand name and generic anti-epileptic drugs. Subjects will take a brand name and a generic drug of the same intervention. While there are only 2 sequences, there are 8 possible drugs for this study, and a study patient will only take 1 out of 8 study drugs. Only pharmacists will know which sequence each patient is assigned to.
  • Drug: Divalproex Sodium (brand name vs generic drugs)
    This is a cross-over replicate study with 2 sequences (arms) comparing brand name and generic anti-epileptic drugs. Subjects will take a brand name and a generic drug of the same intervention. While there are only 2 sequences, there are 8 possible drugs for this study, and a study patient will only take 1 out of 8 study drugs. Only pharmacists will know which sequence each patient is assigned to.
  • Drug: Carbamazepine (brand name vs generic drugs)
    This is a cross-over replicate study with 2 sequences (arms) comparing brand name and generic anti-epileptic drugs. Subjects will take a brand name and a generic drug of the same intervention. While there are only 2 sequences, there are 8 possible drugs for this study, and a study patient will only take 1 out of 8 study drugs. Only pharmacists will know which sequence each patient is assigned to.
  • Drug: Lamotrigine (brand name vs generic drugs)
    This is a cross-over replicate study with 2 sequences (arms) comparing brand name and generic anti-epileptic drugs. Subjects will take a brand name and a generic drug of the same intervention. While there are only 2 sequences, there are 8 possible drugs for this study, and a study patient will only take 1 out of 8 study drugs. Only pharmacists will know which sequence each patient is assigned to.
  • Drug: levetiracetam (brand name vs generic drugs)
    This is a cross-over replicate study with 2 sequences (arms) comparing brand name and generic anti-epileptic drugs. Subjects will take a brand name and a generic drug of the same intervention. While there are only 2 sequences, there are 8 possible drugs for this study, and a study patient will only take 1 out of 8 study drugs. Only pharmacists will know which sequence each patient is assigned to.
  • Drug: Topiramate (brand name vs generic drugs)
    This is a cross-over replicate study with 2 sequences (arms) comparing brand name and generic anti-epileptic drugs. Subjects will take a brand name and a generic drug of the same intervention. While there are only 2 sequences, there are 8 possible drugs for this study, and a study patient will only take 1 out of 8 study drugs. Only pharmacists will know which sequence each patient is assigned to.
  • Drug: Zonisamide (brand name vs generic drugs)
    This is a cross-over replicate study with 2 sequences (arms) comparing brand name and generic anti-epileptic drugs. Subjects will take a brand name and a generic drug of the same intervention. While there are only 2 sequences, there are 8 possible drugs for this study, and a study patient will only take 1 out of 8 study drugs. Only pharmacists will know which sequence each patient is assigned to.
  • Drug: Phenytoin sodium (brand name vs generic drugs)
    This is a cross-over replicate study with 2 sequences (arms) comparing brand name and generic anti-epileptic drugs. Subjects will take a brand name and a generic drug of the same intervention. While there are only 2 sequences, there are 8 possible drugs for this study, and a study patient will only take 1 out of 8 study drugs. Only pharmacists will know which sequence each patient is assigned to.
Study Arms  ICMJE
  • Active Comparator: Sequence 1
    This is a crossover study with 4 treatment periods consisting of 2 Test periods(generic drug) and 2 Reference periods (brand name drug). Each treatment period lasts about 2 weeks, and patients will be randomized into one of the two sequences. All drugs are administered orally, and dosage will depend on a patient.
    Interventions:
    • Drug: Oxcarbmazepine (brand name vs generic drugs)
    • Drug: Divalproex Sodium (brand name vs generic drugs)
    • Drug: Carbamazepine (brand name vs generic drugs)
    • Drug: Lamotrigine (brand name vs generic drugs)
    • Drug: levetiracetam (brand name vs generic drugs)
    • Drug: Topiramate (brand name vs generic drugs)
    • Drug: Zonisamide (brand name vs generic drugs)
    • Drug: Phenytoin sodium (brand name vs generic drugs)
  • Active Comparator: Sequence 2
    This is a crossover study with 4 treatment periods consisting of 2 Test periods(generic drug) and 2 Reference periods (brand name drug). Each treatment period lasts about 2 weeks, and patients will be randomized into one of the two sequences. All drugs are administered orally, and dosage will depend on a patient.
    Interventions:
    • Drug: Oxcarbmazepine (brand name vs generic drugs)
    • Drug: Divalproex Sodium (brand name vs generic drugs)
    • Drug: Carbamazepine (brand name vs generic drugs)
    • Drug: Lamotrigine (brand name vs generic drugs)
    • Drug: levetiracetam (brand name vs generic drugs)
    • Drug: Topiramate (brand name vs generic drugs)
    • Drug: Zonisamide (brand name vs generic drugs)
    • Drug: Phenytoin sodium (brand name vs generic drugs)
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 17, 2018)
17
Original Estimated Enrollment  ICMJE
 (submitted: March 8, 2016)
12
Actual Study Completion Date  ICMJE September 4, 2018
Actual Primary Completion Date August 2, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Subject previously completed BEEP2a study, found to be probably GB, and able to provide informed consent or subject's legally authorized representative is able to provide informed consent.
  2. Subject is male or female between 18 and 76 years of age inclusive.
  3. Subject has a diagnosis of epilepsy including focal or primary generalized epilepsy.
  4. Subject is taking at least one study antiepileptic drug for the treatment of epilepsy.
  5. Subject is an acceptable candidate for venipuncture.
  6. Subject is willing to be switched between brand and generic drug.
  7. Subject is willing to stop all non-routine OTC medications for 24 hours prior to and during pharmacokinetic study visits.
  8. Subject is willing to maintain stable doses of all other AEDs, including Vagus Nerve Stimulation parameters for the duration of the study.

Exclusion Criteria:

  1. Subject has any medical condition, including a progressive neurological condition, which in the opinion of the investigator, could jeopardize the subject's health or would compromise the subject's ability to participate in the trial.
  2. Subject has a history of alcohol or drug abuse, which in the opinion of the investigator, could jeopardize the subject's health or would compromise the subject's ability to participate in this trial.
  3. Subject has a history of previous or current significant psychiatric disorder that would interfere with conduct of the study.
  4. Subject is pregnant or lactating.
  5. Subject has severe liver impairment as assessed by alanine aminotransferase (ALT), aspartate aminotransferase (AST), or total bilirubin levels ≥10 times the upper limit of normal (ULN).
  6. Subject has severe renal impairment as assessed by creatinine clearance lower than 30mL/min, using the Cockcroft-Gault formula.
  7. Female subjects of childbearing potential will not be eligible to participate who are unwilling or unable to use a medically acceptable method of contraception throughout the entire study period and for one week after the study is completed. Medically acceptable methods of contraception that may be used by the subject and/or her partner are: condom with spermicide, diaphragm with spermicide, IUD without progesterone, vaginal spermicidal suppository, surgical sterilization of their partner(s) or abstinence.
  8. Subject is not willing or able to be adherent to study protocol (e.g. study medication dosing and any interacting comedication).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 76 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02707965
Other Study ID Numbers  ICMJE 15-107D
HHSF223201400188C ( Other Grant/Funding Number: USFDA )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: There is no plan to make individual participant data available.
Responsible Party Food and Drug Administration (FDA)
Study Sponsor  ICMJE Food and Drug Administration (FDA)
Collaborators  ICMJE University of Maryland
Investigators  ICMJE
Principal Investigator: James E Polli, Ph.D University of Maryland School of Pharmacy
PRS Account Food and Drug Administration (FDA)
Verification Date October 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP