Equivalence Among Antiepileptic Drug Generic and Brand Products in People With Epilepsy: Single-Dose 6-Period Replicate Design (EQUIGEN Single-Dose Study)

NCT01733394 | Completed Phase 4 DMC

• 2 other identifiers: EQUIGEN Single Dose Protocol005-1005
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 8

Brief Summary

The United States Food and Drug Administration (FDA) has specific rules which generic drug companies must follow to get a generic copy of a seizure medication approved. Currently, FDA approves generic drugs by requiring studies on normal volunteers who don't have epilepsy and who take just one dose of the generic drug followed by a series of blood tests. Some people with epilepsy and their physicians have complained about side effects or loss of seizure control when taking generic drugs, but no one knows if these complaints are truly because of problems with the generic drugs. This research is to determine whether several different generic versions and the brand version of the medication lamotrigine perform in a similar way when given to people with epilepsy. The study drug Lamictal® (lamotrigine) and both of the generic forms of lamotrigine to be tested are approved by the FDA for the treatment of seizures.

Conditions

Epilepsy

Keywords

Epilepsy; Generic

Outcome Measures

Primary Outcomes (1)

• Bioequivalence for generic 1 compared to generic 2

  To determine if Cmax or AUC are significantly different in the high generic product compared to the low generic product taking one as the reference and the other as the test product. Bioequivalence will be established per the current FDA ABE criteria if the 90% confidence interval of the geometric mean of Cmax and AUC for the high generic product compared to the low generic product are entirely within the 80%-125% range using the two one-sided standard analyses

  18 months

Secondary Outcomes (1)

• Intra-subject variances

  18 months

Other Outcomes (4)

• Individual Bioequivalence

  18 months

• Bioequivalence for subjects receiving inducers compared to not receiving inducers

  18 months

• Bioequivalence by gender

  18 months

Study Arms (3)

Generic A - Generic B - Brand - Generic A - Brand - Generic B

EXPERIMENTAL

Sequence 1

Drug: Lamotrigine Generic "A" Lamotrigine Generic "B" Lamotrigine "Brand"; Drug: lamotrigine

Generic B - Brand - Generic A - Generic B - Generic A - Brand

EXPERIMENTAL

Sequence 2

Drug: Lamotrigine Generic "A" Lamotrigine Generic "B" Lamotrigine "Brand"; Drug: lamotrigine

Brand - Generic A - Generic B - Brand - Generic B- Generic A

EXPERIMENTAL

Sequence 3

Drug: Lamotrigine Generic "A" Lamotrigine Generic "B" Lamotrigine "Brand"; Drug: lamotrigine

Interventions

Lamotrigine Generic "A" Lamotrigine Generic "B" Lamotrigine "Brand" DRUG

Also known as: Lamotrigine

Brand - Generic A - Generic B - Brand - Generic B- Generic A; Generic A - Generic B - Brand - Generic A - Brand - Generic B; Generic B - Brand - Generic A - Generic B - Generic A - Brand

lamotrigine DRUG

Brand - Generic A - Generic B - Brand - Generic B- Generic A; Generic A - Generic B - Brand - Generic A - Brand - Generic B; Generic B - Brand - Generic A - Generic B - Generic A - Brand

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Eligible subjects must satisfy the criteria below at the time of enrollment:
• years or older.
• BMI not less than 18.5 and weight not less than 110 pounds.
• Not donated blood within the past 56 days before the first pharmacokinetic testing.
• Agrees not to donate blood at any time during the trial and for 56 days after the final PK in-facility admission.
• Has epilepsy for at least one year based on site PIs assessment.
• Taking at least one AED, which is not the study medication (lamotrigine).
• No changes in AED regimen for at least 28 days prior to first pharmacokinetic testing.
• Have the ability to understand the informed consent form and be willing to provide informed consent.
• Willing to remain on same AED regimen through entire study. Subjects will be responsible to supply all of their concomitant medications (except for the study medication, lamotrigine).
• Willing to stay approximately 14 hours in the research facility on six separate occasions for pharmacokinetic testing.
• Willing to fast overnight and the morning of each of the six pharmacokinetic testing sessions.
• Willing to have at least 23 blood samples collected during the pharmacokinetic testing including the in-facility session and each of the following four mornings for 96 hours post the study medication dose to complete the sample collection for each of the 6 periods. The in-facility blood collections will mainly be performed using an inserted catheter. In the event of difficulty with the catheter, samples may be drawn by venipuncture. The outpatient collections will be drawn by venipuncture. The total amount of blood during each PK session will be equal to about 14 teaspoons (66.5 milliliters). The total amount of blood drawn throughout the entire study will be about 96 teaspoons (478.5 milliliters) or less. For reference, this amount is approximately equal to the quantity of blood drawn during a standard blood donation by the Red Cross.
• Willing to completely abstain from alcohol consumption for at least 24 hours prior to each pharmacokinetic testing admission until after the last sample is drawn for each period (\~96 hours after the initial dose at each pharmacokinetic admission). We encourage no or minimal alcohol use throughout the study, but alcohol is not restricted at other times.
• Willing to remain on a consistent regimen of concomitant medications including over-the-counter drugs and herbal drugs, if they are being used and deemed to possibly affect the metabolism of the study medication.

You may not qualify if:

• Progressive CNS disorder that could influence adverse effects or seizure control.
• Known medication non-adherence. Non-adherence is assessed by the investigator based on the procedures defined in the manual of procedures.
• Taking the study medication (lamotrigine) within 28 days of enrollment.
• Use of valproate (as divalproex sodium or valproic acid), any form of estrogens, rifampin, orlistat, felbamate or sertraline within 28 days of study entry.
• Subject has a history of alcohol or substance abuse within 1 year prior to screening for study participation, or is currently using alcohol, drugs of abuse, or any prescribed or over-the-counter medication in a manner, which, in the opinion of the Investigator, indicates abuse.
• History of psychogenic seizures within the past 2 years.
• Any clinically significant psychiatric illness or psychological or behavioral problem which, in the opinion of the investigator, could interfere with the subject being able to participate in the study or comply with the study requirements. .
• Any clinically significant laboratory abnormality or illness which, in the opinion of the investigator, could interfere with the conducting or interpretation of the study or put the subject at risk.
• History of allergic reaction with past use of the study medication (lamotrigine).
• More than two allergic reactions (actual allergy, not medication intolerance) to an AED or one serious hypersensitivity reaction to an AED.
• History of adverse effect associated with past use of the study medication (lamotrigine) which, in the opinion of the investigator, could pose substantial risk to the subject if it occurred during the trial.
• Pregnant or lactating within 56 days of enrollment.
• Unstable seizure control that makes AED changes likely during the course of the study.
• Use of rescue AEDs (e.g. benzodiazepines) during more than two weeks of the 2 months prior to enrollment.
• Subject is in the process of quitting smoking within 28 days of study entry or plans to quit smoking during the period of time the study will be conducted.

Sponsors & Collaborators

• University of Cincinnati: lead
• American Epilepsy Society: collaborator
• Epilepsy Foundation: collaborator

Study Sites (8)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Drake University

Des Moines, Iowa, 50311-4505, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

University of Kansas

Kansas City, Kansas, 66160, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642-8673, United States

Location

University of Cincinnati Medical Center

Cincinnati, Ohio, 45267-0525, United States

Location

University of Wisconsin-Madison

Madison, Wisconsin, 53705, United States

Location

Related Publications (1)

• Berg M, Welty TE, Gidal BE, Diaz FJ, Krebill R, Szaflarski JP, Dworetzky BA, Pollard JR, Elder EJ Jr, Jiang W, Jiang X, Switzer RD, Privitera MD. Bioequivalence Between Generic and Branded Lamotrigine in People With Epilepsy: The EQUIGEN Randomized Clinical Trial. JAMA Neurol. 2017 Aug 1;74(8):919-926. doi: 10.1001/jamaneurol.2017.0497.

  PMID: 28654954 DERIVED

MeSH Terms

Conditions

Epilepsy

Interventions

Lamotrigine

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Triazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Michael D. Privitera, MD

  University of Cincinnati

  PRINCIPAL INVESTIGATOR

• Michel J Berg, MD

  University of Rochester

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director Cincinnati Epilepsy Center

Study Record Dates

• First Submitted: November 2, 2012
• First Posted: November 27, 2012
• Study Start: December 12, 2012
• Primary Completion: September 26, 2016
• Study Completion: September 26, 2016
• Last Updated: July 19, 2017

Record last verified: 2017-07

Locations

US (8)