An open label, randomized, single-dose, two-sequences, two-periods, crossover study to assess the bioequivalence of perampanel in Lepsiramp 0.5mg/ml oral suspension (Test product) in comparison with Fycompa® 0.5mg/ml oral suspension (Reference product) in healthy subjects under fasting conditions.
This was a single-dose, open-label, randomized, two-sequence, two-period crossover bioequivalence study conducted under fasting conditions at Advanced Research Center (ARC), Cairo, Egypt in 2024. The study compared the bioequivalence of Lepsiramp 0.5 mg/mL oral suspension (Test) with Fycompa® 0.5 mg/mL oral suspension (Reference), both formulations containing perampanel. Study Design Participants were randomized in a 1:1 ratio to receive the test or reference product across two study periods, separated by a 6-week washout. Each subject received a single 24 mL oral dose (equivalent to 12 mg perampanel) under fasting conditions. A standardized diet was provided during each period, and fluid intake was controlled pre- and post-dosing to maintain consistency. Blood Sampling Details In each period, 22 blood samples (5 mL each) were collected to characterize the plasma concentration-time profile. A forearm vein cannula was used for samples up to 24 hours; later samples were collected via venipuncture. Samples were centrifuged at 3500 rpm for 5 minutes at 4°C. Plasma was separated and stored at -80°C pending analysis. Pharmacokinetic and Bioanalytical Methods Plasma perampanel concentrations were quantified using a validated LC-MS/MS method with a calibration range of 3-400 ng/mL. The primary PK parameters included Cmax and AUC₀-₇₂, while secondary parameters were Tmax, AUC₀-inf, t½, and ke. PK analysis was conducted using Phoenix WinNonlin (v8.3.4), with calculations based on actual sampling times. Bioequivalence Evaluation Bioequivalence was determined if the 90% confidence intervals (CIs) for the geometric mean ratios (GMRs) of Cmax and AUC₀-₇₂ fell within the 80-125% range. ANOVA was applied to log-transformed data for Cmax and AUC, and Wilcoxon signed-rank test was used for Tmax comparisons. Safety Evaluation Subjects were monitored for adverse events throughout the study. Vital signs were assessed at multiple time points (pre-dose, and 2, 6, 12, and 72 hours post-dose). Complete blood counts were performed at the study's end. Statistical Analysis Sample size was calculated using R (v4.2.1), assuming a 19.35% intra-subject variability for Cmax, with 80% power, 5% significance level, and adjustment for expected dropouts. The Two One-Sided Tests (TOST) procedure was applied to log-transformed PK parameters to assess bioequivalence.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
26
Test product
Reference product
Advanced Research Center (ARC)
Cairo, Cairo Governorate, Egypt
Cmax
Peak plasma concentration
Time frame: From time zero up to 72 hours in each study period
AUC(0-72)
The area under the plasma concentration-time curve up to 72 hours
Time frame: From time zero up to 72 hours in each study period
Tmax
The time of the peak plasma concentration
Time frame: From time zero up to 72 hours in each study period
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