Bioequivalence of Testosterone Transdermal Gel in Healthy Female Subjects

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Laboratorios Leon Farma S.A.

Participant type

Healthy volunteers

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Hormonal diseases [C19]

Trial duration

2 May 2023 → 31 Jul 2023

Decision date (initial)

2023-01-30

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Laboratorios León Farma, S.A.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Bioequivalence, Safety

To compare the bioavailability between Test and Reference products.

Secondary objectives 1

1. To assess the safety and tolerability of Test product.

Conditions and MedDRA coding

Male hypogonadism

Study design 4 periods

Regulatory references

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Free written informed consent prior to any procedure required by the study.
2. Female subject between 45 and 65 years, inclusive, at the time of signing the informed consent.
3. Post-menopausal, defined as amenorrhea for at least 12 months without an alternative medical cause, or history of hysterectomy and bilateral oophorectomy at least 6 months prior to Screening.
4. Blood follicle stimulating hormone (FSH) compatible with post-menopausal state (23 - 116.3 IU/L).
5. Body mass index (BMI) of 18.5 to 30.0 kg/m2, inclusive.
6. No clinically relevant diseases captured in medical history.
7. No clinically relevant abnormalities on physical examination (including detailed skin examination and vital signs).
8. No clinically relevant abnormalities on 12-lead ECG.
9. No clinically relevant abnormalities on clinical laboratory tests.
10. Non-smoker or ex-smoker (i.e. someone who abstained from using tobacco- or nicotine-containing products for at least 3 months prior to Screening).
11. Willingness to accept and comply with all study procedures and restrictions.
12. Negative SARS-CoV-2 test or valid EU Digital COVID-19 Recovery Certificate.

Exclusion criteria 39

1. Known hypersensitivity/allergy reaction to any of the ingredients of the study products.
2. Known severe hypersensitivity reaction to any other drug.
3. Any general condition or local condition (e.g. skin disorder) that may affect drug pharmacokinetics (absorption, distribution, metabolism or excretion) or subject safety.
4. Known or suspected carcinoma of the breast.
5. Abnormal genital bleeding.
6. Thrombophilia or thromboembolic disorder.
7. History of heart failure.
8. History of diabetes.
9. Migraine or epilepsy.
10. History of significant dermatological problems (e.g., severe or cystic acne) or concomitant skin disease within the last 5 years, or a history of drug-induced contact dermatitis.
11. Use of hormonal replacement therapy within the previous 6 months.
12. Blood hemoglobin below the lower limit of the normal range.
13. Blood ferritin below the lower limit of the normal range.
14. Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) above the upper limit of the normal range.
15. Estimated renal creatinine clearance (CrCL) below the lower limit of normal range (80-110 mL/min), based on creatinine clearance calculation by the Cockcroft-Gault formula and normalized to an average body surface area of 1.73 m2.
16. Positive test results for hepatitis B surface antigen (HBsAg), anti-hepatitis C virus antibodies (anti-HCV) or anti-human immunodeficiency virus antibodies (HIV-1 and HIV-2 Ab).
17. SBP >150 mmHg and/or DBP >90 mmHg, measured on the dominant arm, after at least 3 minutes in seated position.
18. Positive result in drugs-of-abuse or ethanol tests.
19. Use of a depot injection or an implant of any drug within the previous 6 months.
20. Average weekly alcohol consumption of >7 units within the previous 6 months.
21. Average daily consumption of methylxanthines-containing beverages or food (e.g. coffee, tea, cola, sodas, chocolate) equivalent to >500 mg methylxanthines.
22. Participation in any clinical trial within the previous 2 months.
23. Participation in more than 2 clinical trials within the previous 12 months.
24. Blood donation or significant blood loss (≥ 450 mL) due to any reason or had plasmapheresis within the previous 2 months.
25. Difficulty in fasting or any dietary restriction such as lactose intolerance, vegan, lowfat, low sodium, etc., that may interfere with the diet served during the study.
26. Veins unsuitable for intravenous puncture on either arm.
27. Is pregnant or breast-feeding.
28. Presence of a skin condition or scar tissue that could interfere with absorption, skin irritation/tolerability assessments, or assessment of any reaction to study drugs.
29. Any other condition that the Investigator considers to render the subject unsuitable for the study.
30. Any recent disease or condition or treatment that, according to the Investigator, would put the subject at undue risk due to study participation or occurred at a timeframe in which may interfere with the pharmacokinetics of study drug.
31. Use of any method of hair removal (e.g. waxing, shaving, epilating, laser, tweezers) at the application site within the previous 5 days.
32. Sunbathing or using tanning beds at the application site within the previous 2 days.
33. Use of topical products containing medication (including creams, oils, lotions, ointments, gels, topical solutions or patches) at the application site within the previous 14 days.
34. Use of topical products not containing medication (including make-up, sunscreen, creams, oils, lotions, powders, alcohol) at the gel application site within the previous 2 days.
35. Use of saunas or swimming within 2 days prior to admission.
36. Use of prescription or non-prescription medicinal products (such as vitamins, food supplements and herbal supplements, including St John’s Wort) within the previous 14 days, unless in the Investigator’s opinion the medication does not interfere with the pharmacokinetics of study drug or compromise subject safety.
37. Consumption of Seville oranges, pomelo, pomegranate, starfruit or grapefruit products (fresh, canned, or frozen) within the previous 7 days.
38. Positive result in drugs-of-abuse or ethanol tests.
39. Any other condition that the investigator considers to render the subject unsuitable for the study period.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Cmax and AUC0-t estimated from baseline corrected testosterone will be the primary pharmacokinetic parameters, AUC0-∞ will be the secondary pharmacokinetic parameter.

Secondary endpoints 1

1. Safety assessments will include physical examination, detailed skin examination, vital signs, 12-lead ECG, clinical laboratory tests, skin irritation/tolerability assessments and adverse events (AEs) monitoring.

Investigational products

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

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Laboratorios Leon Farma S.A.

Sponsor organisation

Laboratorios Leon Farma S.A.

Address

Calle La Vallina S/n

City

Villaquilambre

Postcode

24193

Country

Spain

Scientific contact point

Organisation

Laboratorios Leon Farma S.A.

Contact name

Jorge Avilés

Public contact point

Organisation

Laboratorios Leon Farma S.A.

Contact name

Jorge Avilés

Third parties 2

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

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