Bioequivalence Assessment Between Two Perampanel Oral Suspension Formulations

Single-dose, Randomized, Two-period, Two-sequence Crossover Study to Evaluate the Bioequivalence of Lepsiramp 0.5mg/ml Oral Suspension (Test) and Fycompa® 0.5mg/ml Oral Suspension (Reference) Under Fasting Conditions

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.

Study Overview

• Status: Completed
• Conditions: Bioequivalence Study in Healthy Subjects
• Intervention / Treatment: Drug: Lepsiramp, 0.5 Mg/mL Oral Suspension; Drug: Fycompa, 0.5 Mg/mL Oral Suspension

Detailed Description

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
• Enrollment (Actual): 26
• Phase: Phase 1

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt
    • Advanced Research Center (ARC)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Healthy male and female subjects aged between 18 and 55 years.
2. Non-smokers or mild smokers with a maximum limit of 5 cigarettes/day.
3. Normal physical examinations at screening visit.
4. Having BMI ranged between 18.5-30 kg/m2.
5. Ability to communicate adequately with the clinical staff.
6. Ability and agreement to comply with the study requirements.

7. Normal BP and HR measured under stabilized conditions.

   • The Blood pressure is considered normal if the SBP falls within 100 to 140 mmHg, and the DBP within 60 to 90 mmHg.
   • The heart rate normal range is from 60 to 100 bpm.
   • Respiratory rate normal range is from 12 to 16 breaths per minute.
   • Temperature normal range is from 36.5ºC to 37.5ºC.
8. Normal laboratory results within normal range or with clinically non-significant deviation including: Complete Blood Count, Clinical Chemistry: Random blood sugar, blood urea, creatinine, sodium, potassium, total bilirubin, alanine amino transferase (ALT/GPT), aspartate amino transferase (AST/GOT), alkaline phosphatase, total protein in serum, Lipid profile, urinalysis.
9. Negative Virology tests: HIV (HIV Ab), hepatitis B (HBsAg), hepatitis C (HCV IgG).
10. Negative results for abused drug analysis in urine (Amphetamine (AMP), Barbiturate (BAR), Benzodiazepine (BZO), Cannabinoid (THC), Cocaine, Opiates (Morphine (MOP), Tramadol (TRA)).
11. Understanding of the study and agreeing to give a written informed consent.
12. Using an adequate contraception method during the study and for at least 30 days after the study (for potential subjects).

Exclusion Criteria:

1. Subjects who have atopic constitution, asthma or known allergy for the API under investigation and/or any other ingredients of the investigational product.
2. Presence of clinical relevance of cardiovascular, neurological, musculoskeletal, hematological, hepatic, gastrointestinal, renal, pulmonary, endocrinological, metabolism or psychiatric disease.
3. Symptomatic or asymptomatic orthostatic hypotension at screening defined by a decrease of SBP more than 20 mmHg or DBP more than 10 mmHg occurs between sitting/supine to standing position. The subject will be excluded (if the drug under investigation has antihypertensive properties or documented to have orthostatic hypotension as a side effect).
4. Presence or history of malabsorption or any gastrointestinal surgery except appendectomy or herniotomy.
5. Subjects who have given more than 400 mL blood within the last two months before the first drug administration and subjects who have participated in any drug research within the last two months before the first day of drug administration.
6. Subjects who used any prescribed systemic medication (including OTC medication) within 2 weeks (or six elimination half-lives of this medication, whichever is longer) before the initiation of the study (except for single doses of analgesics which have no drug interaction with study product).
7. Use of any vitamins or herbal products within 3 days prior to the initial dose of the study medication.
8. Subjects who have any chronic disease which might interfere with the absorption, distribution, metabolism or excretion of the drug.
9. Subjects who consumed grapefruit or grapefruit juice during 48 hr prior to drug administration, during the study.
10. History of alcohol abuse and/or regular use of more than 2 units of alcohol per day or positive alcohol test.
11. History of difficulty of swallowing.
12. Intake of enzyme-inducing, organ toxic, long half-life drugs within 4 weeks before start of the study
13. Subjects who follow a special diet due to any reason, e.g., vegetarian.
14. Has a recent acute infection.
15. Pregnant females or female subjects who practice lactation or unprotected females with pregnancy potential

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Lepsiramp (perampanel 0.5 mg/mL) oral suspension; Test Product	Drug: Lepsiramp, 0.5 Mg/mL Oral Suspension; Test product; Other Names: Perampanel 0.5mg/mL
Active Comparator: Fycompa® (perampanel 0.5 mg/mL) oral suspension; Reference Product	Drug: Fycompa, 0.5 Mg/mL Oral Suspension; Reference product; Other Names: perampanel 0.5mg/mL

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	Peak plasma concentration	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	From time zero up to 72 hours in each study period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tmax	The time of the peak plasma concentration	From time zero up to 72 hours in each study period

Collaborators and Investigators

• Sponsor: Aya Mohammed Abdel Magid Abdel Hamid
• Collaborators: Advanced Research Center (ARC); Global Napi Pharmaceuticals for Global Advanced Pharmaceuticals
• Investigators: Study Director: Kamal A. Badr, Ph.D., Advanced Research Center (ARC)

Study record dates

Study Major Dates

• Study Start (Actual): March 7, 2024
• Primary Completion (Actual): July 23, 2024
• Study Completion (Actual): July 23, 2024

Study Registration Dates

• First Submitted: April 29, 2025
• First Submitted That Met QC Criteria: May 9, 2025
• First Posted (Actual): May 14, 2025

Study Record Updates

• Last Update Posted (Actual): August 20, 2025
• Last Update Submitted That Met QC Criteria: August 15, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Epilepsy; Bioequivalence; Perampanel; Oral suspension
• Other Study ID Numbers: BE0124LEP0.5-GAP/01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is not a plan to make IPD available.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No