An Open-Label, One-Sequence Study to Evaluate the Steady-State Comparative Bioavailability of Quarterly Letrozole SIE and Once Daily 2.5 mg Oral Letrozole (Femara®) in Post-Menopausal Women Treated With Endocrine Therapy for Hormone Receptor-Positive Early Breast Cancer. (SIE-1)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 120
- 试验地点
- 19
- 主要终点
- Area under the concentration-time curve within a dosing interval at Steady-State (SS AUCtau)
研究概览
简要总结
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.
详细描述
The primary objective of the study is to evaluate the steady-state comparative bioavailability of quarterly injectable Letrozole SIE compared to United States (US)-sourced oral Femara® in the US-sourced arm and of quarterly injectable Letrozole SIE compared to European Union (EU)-sourced oral Femara® in the EU-sourced arm, in post-menopausal women treated with endocrine therapy for hormone-receptor positive (HR+) early breast cancer (EBC). The study also aims to characterize the elimination phase of Letrozole SIE after multiple doses.
The study consists of four periods: Screening, Treatment Period 1 (TP1), Treatment Period 2 (TP2) and Extension Period. After the Screening Period, participants will be randomized to two different arms: US-sourced oral Femara® or EU-sourced oral Femara® for 14 days to achieve the steady-state concentrations of letrozole in TP1. After receiving the latest oral letrozole dose, participants from both arms will start TP2. In TP2, quarterly injectable Letrozole SIE will be administered to achieve steady-state. After TP2, a subset of participants (up to 60 participants, regardless of which study arm they belong to) will continue in the study for the assessment of the elimination phase of Letrozole SIE after multiple doses during the Extension Period.
It is estimated that approximately 120 subjects should be randomized.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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.
- •Women who have undergone breast imaging per applicable guidelines (e.g., mammogram) within the last 12 months with no evidence of malignancy (documentation required), and if not done, must be willing to have 1 performed prior to baseline.
排除标准
- •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 CYP2A
- •Diagnosed with osteoporosis.
- •Preexisting cardiovascular disease
- •Positive result for hepatitis B surface antigen, hepatitis B core antibody, hepatitis C antibody, or HIV antibodies.
研究组 & 干预措施
US-sourced oral Femara®
干预措施: US-sourced oral Femara® + Letrozole SIE (Drug)
EU-sourced oral Femara®
干预措施: EU sourced oral Femara® + Letrozole SIE (Drug)
结局指标
主要结局
Area under the concentration-time curve within a dosing interval at Steady-State (SS AUCtau)
时间窗: After multiple doses of Letrozole SIE until Day 281 TP2 and after multiple doses of US-sourced oral Femara® or EU-sourced oral Femara® on Day 14 TP1
Individual and mean area under the concentration-time curve within a dosing interval at steady-state
次要结局
- Adverse Events(From the time of obtaining signed informed consent until the final follow-up visit on Day 281 (or Day 421 for the subset of participants in the Extension Period))
- Injection site reactions(At pre-dose and 1 hour after each Letrozole SIE administration in TP2)
- Injection-related pain score(From baseline TP2 to the follow-up visit on Day 281)
- Bone mineral density (BMD) by dual energy x-ray absorptiometry (DXA)(From screening to Day 281 TP2)
- Average plasma drug concentration during a dosing interval at Steady-State (SS Cave)(After multiple doses of Letrozole SIE until Day 281 TP2 and after multiple doses of US-sourced oral Femara® or EU-sourced oral Femara® at Day 14 TP1)
- Minimum drug concentration at steady-state (Cmin ss)(After multiple doses of Letrozole SIE until Day 281 TP2 and after multiple doses of US-sourced oral Femara® or EU-sourced oral Femara® at Day 14 TP1)
- Maximum plasma concentration at steady-state (Cmax ss)(After multiple doses of Letrozole SIE at Day 281 TP2 and after multiple doses of US-sourced oral Femara® or EU-sourced oral Femara® at Day 14 TP1)
- Letrozole blood level percent fluctuation(After multiple doses of Letrozole SIE at Day 281 TP2 and after multiple doses of US-sourced oral Femara® or EU-sourced oral Femara® at Day 14 TP1)
- Time to peak observed concentration (Tmax)(After multiple doses of Letrozole SIE until Day 281 TP2 and after multiple doses of US-sourced oral Femara® or EU-sourced oral Femara® at Day 14 TP1)
- Steady-State (SS)(After multiple doses of Letrozole SIE until Day 281 TP2 and after multiple doses of US-sourced oral Femara® or EU-sourced oral Femara® at Day 14 TP1)
- Terminal rate constant (λz)(After multiple doses of Letrozole SIE in TP2 until Day 421 in the Extension Period)
- Terminal half-life (t1/2)(After multiple doses of Letrozole SIE in TP2 until Day 421 in the Extension Period)
- Area under the curve extrapolated to infinity (AUC∞)(After multiple doses of Letrozole SIE in TP2 until Day 421 in the Extension Period)
- Area under the curve that is extrapolated (AUCextrap)(After multiple doses of Letrozole SIE in TP2 until Day 421 in the Extension Period)