Single dose, open-label, laboratory blinded, randomised, 2-treatment, 2-period, 2-sequence, crossover bioequivalence study of test product Perampanel 12 mg film-coated tablets versus reference product Fycompa 12 mg film-coated tablets (Eisai GmbH) in healthy adult male and female subjects under fasting conditions.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Laboratorios Cinfa S.A.

Participant type

Healthy volunteers

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

23 May 2023 → 15 Aug 2023

Decision date (initial)

2023-05-04

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Laboratorios CINFA, S.A.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Bioequivalence

to assess comparative bioavailability of Test (T) and Reference (R) Product

Secondary objectives 1

1. to evaluate safety and tolerability single oral dose of perampanel in Test Product and Reference Product in healthy subjects under fasting conditions

Conditions and MedDRA coding

Not applicable (submitted trial is a bioequivalence study in Healthy Subjects)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Healthy males and non-pregnant and no breast-feeding females*, ≥ 18 and ≤ 55 years of age**(on the day of Informed Consent). * Wonem are tested for pregnancy during screening and check-in procedure for each Period and also during the exit examination. ** The upper age limit is set due to higher probability of co-morbidities above 55 years and to avoid unnecessary screening of too many subjects.
2. Non-smoker or past-smoker (who has stopped smoking at least 6 months before the first dosing).
3. Body Mass Index (BMI) ≥ 18.5 and ≤ 30.0 kg/m2 (on the day of screening).
4. Subject is available for the whole study and has provided his/her written informed consent.
5. Subjects in good health, as determined by screening medical history, physical examination, vital signs assessments (heart rate, systolic and diastolic blood pressure, and body temperature) and 12-lead ECG. Minor deviations outside the reference ranges will be acceptable, if deemed not clinically significant by the Investigator.
6. All laboratory screening results within the normal range, possible deviations will be deemed clinically insignificant by the Investigator.
7. Acceptance of use of highly effective contraceptive measures during the whole study by female subjects of childbearing potential and contraceptive measures during the whole study by male subjects*. * Methods of highly effective contraception for female subjects of childbearing potential: - combined (oestrogen and progestogen containing) hormonal contraception, either oral, intravaginal or transdermal or - progestogen-only hormonal contraception associated with inhibition of ovulation, either oral, injectable or implantable or - intrauterine hormone-releasing system or - bilateral tubal occlusion or - vasectomised (sterilised) partner (if it is a sole sexual partner of the subject and medical assessment of the surgical success has been provided to the partner) or - intrauterine device (non-hormonal) since at least 30 days prior to the first dosing and use one of the barrier methods or - abstinence from any sexual intercourse (If this is in line with your preferred and routine lifestyle.) Hormonal intrauterine device or oral hormonal contraceptives or hormonal replacement therapy should be taken without significant changes in dose for 90 days before the first dosing and without change during the study. Highly effective contraception must be combined with use of barrier method with spermicide (condom, diaphragm), because perampanel decreases efficacy of hormonal progestogen containing contraception. Recommended methods of contraception for male subjects: - If a female partner of male participant in the study is of childbearing potential, the couple needs to use the above described highly effective contraception methods. - If a female partner of male participant in the study is pregnant, the recommended contraception method is that the male must use a barrier method (condom). Premenarcheal women, women with documented hysterectomy, bilateral salpingectomy, bilateral oophorectomy and postmenopausal women are not considered of childbearing potential. Postmenopausal state is defined as no menses for 12 months without an alternative medical cause. The appropriate contraceptive measures must be used during this study and at least 40 days after the study completion.
8. The subject speaks and understands Czech fluently.

Exclusion criteria 25

1. Acute or chronic diseases and/or clinical finding which may interfere with the aims of the study or with the drug’s safety, tolerability, bioavailability and/or pharmacokinetics of the IMP.
2. History of significant hypersensitivity to used IMP, or any related products (including excipients of the formulations) as well as severe hypersensitivity reactions (like angioedema) to any drugs.
3. Serious mental disease and/or inability to cooperate with clinical team.
4. Abuse of drugs, alcohol (≥ 40 g for men or ≥ 20 g for women of pure ethanol per day), solvents or the inability to give up the consumption of foods containing methylxanthine (such as coffee, tea, mate, cocoa, guarana, cola, energy drinks, chocolate...) in the period from 48 hours before each drug administration until the last blood draw in each study period.
5. Clinically significant illness within 28 days before the first dosing, including major surgery.
6. Any systemic over-the-counter (OTC) drug treatment and/or vitamins and/or herbal treatment (e.g Saint John´s Wort) and/or food supplements within 14 days before the first dosing.
7. Any systemic prescription treatment within 28 days before the first dosing, except hormonal contraceptives or substitution taken without significant changes in dose for 90 days prior to the first dosing.
8. Use of organ-toxic drugs or systemic drugs known to substantially alter liver metabolism within 90 days before the first dosing.
9. Donation or loss of at least 500 mL of blood within 90 days or donation of plasma or platelets within 14 days before the first dosing.
10. Getting a tattoo, body piercing or any cosmetic treatment involving skin piercing within 90 days before screening, unless evaluated by Investigator as non-significant for inclusion in the study.
11. Positive urine drugs abuse test result at screening or at check-in.
12. Positive result of alcohol breath test at screening or at check-in.
13. Positive result of urine cotinine test at screening.
14. Female subjects with positive result of blood pregnancy test at screening or positive urine pregnancy test at check-in or breast-feeding or lack of results of pregnancy test.
15. Body temperature ≥ 37.0 °C at screening or at check-in.
16. Sitting blood pressure after a minimum of 5 minutes of rest is out of the range of 90-140 mmHg for systolic BP and/or 60-90 mmHg for diastolic BP and/or heart rate out of the range of 50-100 bpm during the screening procedure.
17. Positive result of HBsAg and/or HCV and/or HIV test during screening procedure.
18. Anaemia, haemoglobin below 120 g/L for women and 130 g/L for men at the screening.
19. Participation in another clinical study within 30 days (i. e. from the day of exit procedure in previous study until the day of the first dosing of this study).
20. History of previous or current liver diseases with elevations in serum transaminases (ALT or AST more than 3x ULN).
21. History of rare hereditary problems with intolerance of galactose, lactase deficiency or glucose-galactose malabsorption.
22. History of suicidal or homicidal behaviour, tendencies toward such behaviour, or previous attempts.
23. Subject was vaccinated against COVID-19 less than 14 days before the screening and/or subject plans to be vaccinated against COVID-19 during the study.
24. Subjects was hospitalized for COVID-19 related reasons.
25. Positive PCR on SARS-Cov-2 or positive antigen test, if required for safety reasons before hospitalization in the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Cmax and AUC(0-72h) – as per truncated design; 90% confidence intervals for the T/R ratio of LSM for perampanel based on ln-transformed data will be calculated and compared with acceptance limits: AUC(0-72h) 80.00 – 125.00%, Cmax 80.00 – 125.00%.

Secondary endpoints 1

1. tmax

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Laboratorios Cinfa S.A.

Sponsor organisation

Laboratorios Cinfa S.A.

Address

Travesia Roncesvalles 1

City

Olloki

Postcode

31699

Country

Spain

Scientific contact point

Organisation

Laboratorios Cinfa S.A.

Contact name

Medical Department

Public contact point

Organisation

Laboratorios Cinfa S.A.

Contact name

Medical Department

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 2 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications