Bioequivalence Between Generic, Branded Lamotrigine in People With Epilepsy



Title: Bioequivalence Between Generic and Branded Lamotrigine in People With Epilepsy

Berg, M et al.


 

What You Need to Know:

The disparate lamotrigine products evaluated during the Equivalence Among Antiepileptic Drug Generic and Brand Products in People With Epilepsy (EQUIGEN) study were found to be bioequivalent when analyzed in patients with epilepsy using concomitant antiepileptic medications.

Trial Design:

  • Crossover, prospective, replicate pharmacokinetic trial evaluated the bioequivalence of 3 immediate-release lamotrigine drug products currently marketed (included 1 branded and 2 generic drug products)
  • 50 adults with epilepsy were enrolled in the study; patients were taking concomitant antiepileptic medications, however were not currently receiving treatment with lamotrigine
  • “Every participant was randomly assigned to 1 of 3 equivalent sequences, each comprising 6 study periods, during which they had blood draws before and after medication administration”
  • One single-dose of 25mg immediate-release lamotrigine was administered to each patient at the initiation of each study period; each drug product was studied twice
  • Patients and study investigators were blinded to the generic products utilized during the study
  • Primary endpoint: bioequivalence; comparisons of maximum plasma concentration (Cmax) and area under the concentration-time curve (AUC) were completed, “and average bioequivalence (ABE) was established if the 90% CIs of the ratios of the 2 products were within equivalence limits (80%-125%)”

Key Outcomes:

  • The intention-to-treat analysis included 49 patients
  • “The 3 drug products were considered bioequivalent because the 90% CIs were within equivalence limits (lowest and highest CI limits for Cmax, 92.6% and 110.4%; for AUC0-96, 96.9% and 101.9%)”
  • Replicate testing: no significant differences were observed in within-subject variability across the 3 drug products (likelihood ratios, χ22 for log-transformed variables: AUC0-96, 2.58; Cmax, 0.64; and AUC0-00, 4.05; P ≥ .13)
  • Scaled ABE and individual bioequivalence criteria: demonstrated bioequivalence across all 3 drug products and no subject x formulation interaction (Cmax, 0.00; AUC0-96, 0.54; and AUC0-00 0.36; P ≥ .76)