The study aims to compare the amount of the drug letrozole that gets into the bloodstream after multiple doses of the quarterly injection Letrozole SIE, versus multiple doses of the standard oral daily tablet of letrozole (Femara®), in women who have gone through menopause and have received treatment for hormone receptor-positive early breast cancer. Participants must have completed at least five years of hormone therapy with at least two of those years with letrozole before starting their participation in the study. Women who have completed four years of hormone therapy are also eligible if their doctor considers them at low risk of cancer returning.
Women with weight of ≥50 kg and a Body Mass Index (BMI) ≥19 kg/m2 and ≤39 kg/m2
Postmenopausal women.
Women with confirmed diagnosis of HR+/HER2- or HR+/HER2+ early stage breast cancer who have completed at least 5 years of endocrine therapy, at least 2 years of which were with letrozole. Participants at a low risk of relapse, as assessed by the investigator, can also be eligible after completing 4 years of adjuvant endocrine therapy, at least 2 of which were with letrozole.
Women in good health.
Presence of an uncontrolled, unstable, clinically significant medical condition.
Have used estrogen or progesterone systemic or topical therapy, oral contraceptives, androgens, LH-releasing hormone analogs, prolactin inhibitors, or antiandrogens within 3 months prior to screening.
Use of inducers or inhibitors of CYP3A4 and CYP2A6.
Diagnosed with osteoporosis.
Parallel
US-sourced oral Femara® + Letrozole SIE
DrugUS-sourced Femara® 2.5 mg/day oral for 14 days (treatment period 1) + quarterly injectable Letrozole SIE (treatment period 2)
EU sourced oral Femara® + Letrozole SIE
DrugEU-sourced oral Femara® 2.5 mg/day for 14 days (treatment period 1) + quarterly injectable Letrozole SIE (treatment period 2)
Area under the concentration-time curve within a dosing interval at Steady-State (SS AUCtau)
Individual and mean area under the concentration-time curve within a dosing interval at steady-state
Adverse Events
Incidence of adverse events (type, severity, seriousness, and relationship to study drug), including the incidence of treatment-emergent adverse events (TEAEs), the incidence of serious TEAEs, and the incidence of TEAEs leading to treatment discontinuation.
Injection site reactions
Incidence of injection site reactions
Injection-related pain score
Changes in injection-related pain score by numeric rating scale (NRS). The NRS evaluates the intensity of injection-related pain experienced at the time of Letrozole SIE administration. It is scored from 0 to 10 (0 meaning no pain and 10 meaning the worst possible pain).
Bone mineral density (BMD) by dual energy x-ray absorptiometry (DXA)
Changes in bone mineral density BMD by DXA
Hormone supression
Analysis of letrozole exposure and hormone suppression measuring the sex hormone estrone (E1), sulfate estrone (SE1), and estradiol (E2) plasma levels.
CYP2A6 genotyping
Proportion of participants in each CYP2A6 metabolizer phenotype category (normal, intermediate, slow)
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