A Phase I, Open Label, Dose Escalation Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Single Intramuscular Injections of Letrozole LEBE at Different Strengths in Voluntary Healthy Post-Menopausal Women.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 84
- 试验地点
- 1
- 主要终点
- λz
研究概览
简要总结
This is a Phase I, open label, sequential, single ascending dose (SAD) study to evaluate the pharmacokinetic (PK), safety, and tolerability of Letrozole LEBE in healthy post-menopausal women.
详细描述
The study consists of 1 Screening Period and 2 treatment periods. Evaluation of eligibility and allocation of subject number to the volunteers will be performed after Screening. It is planned that subjects will be enrolled in three groups of approximately 30 subjects in each group (Groups 1 to 3), in order to ensure 15 completed subjects per group in Treatment Period 1 and Treatment Period 2. In Treatment Period 1, each subject will sequentially receive 1 dose daily of oral Femara (2.5 mg) over a period of 14 days followed by a single intramuscular (IM) dose of Letrozole LEBE (after a washout period) in Treatment Period 2. Ascending doses of Letrozole LEBE will be given to Groups 1, 2 and 3. Safety and tolerability will be assessed in all groups by the incidence and severity of Adverse Events (AEs) and Serious AEs (SAEs), concomitant medication use, vital sign assessments, clinical laboratory evaluations, 12 lead ECGs, physical examination, and body weight/BMI. The end of the clinical trial will be the last visit of the last subject at Day 197 of Treatment Period 2 or any additionally required 4-weeks safety follow up visits, when plasma levels of letrozole are detectable, whichever occurs later. Those remaining subjects with detectable plasma levels of letrozole could be followed every 4 weeks.
The sample size was estimated based on a minimum number necessary to obtain a preliminary assessment regarding the drug's PK and safety profile over the planned dose range. No formal sample size calculation was made for this study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Healthy post-menopausal women.
- •Capable of providing informed consent.
- •Weight of ≥50 kg and a BMI ≥19 and ≤39 kg/m
- •Subjects should be able to communicate with clinic staff.
排除标准
- •Subjects who have a history of allergy or hypersensitivity to letrozole or any of the inactive ingredients.
- •Subjects who have a history of galactose intolerance, severe hereditary lactase deficiency glucose-galactose malabsorption.
- •Subjects who have used estrogen or progesterone hormone replacement therapy, thyroid replacement therapy, oral contraceptives, androgens, luteinizing hormone (LH) releasing hormone analogs, prolactin inhibitors, or antiandrogens within prior to Screening.
- •Subjects who have used: any medications including St. John's wort or any medications or products known to be potent or moderate inhibitors of CYP P450 3A
- •Subjects who have been diagnosed with osteoporosis.
- •Subjects who have an abnormality at Screening or prior to first dose that in the opinion of the investigator increases the risk of participating in the study.
- •Subjects who have any clinically significant abnormal physical examination or laboratory safety findings at screening.
- •Subjects who have relevant diseases or clinically significant abnormal relevant findings at Screening, as determined by medical history, physical examination, laboratory, ECG, DEXA, and breast and pelvic examination.
- •Subjects who have history of any significant chronic disease.
- •History of cancer within the past 5 years with the exception of non-melanoma skin cancer.
- •Subjects who have a history of drug-dependence, and recent history of alcoholism or abuse of alcohol.
- •Subjects who have received a drug in research or have participated in other clinical trials within 90 days, prior to dosing.
- •Any other unspecified reason that, in the opinion of the investigator (or designee) or sponsor, makes the subject unsuitable for enrolment.
研究组 & 干预措施
Cohort 3: Letrozol LEBE 225 mg
干预措施: Letrozole LEBE 225 mg (Drug)
Cohort 2: Letrozol LEBE 150 mg
干预措施: Letrozole LEBE 150 mg (Drug)
Cohort 1: Letrozol LEBE 75 mg
干预措施: Letrozole LEBE 75 mg (Drug)
结局指标
主要结局
λz
时间窗: Following single IM administration of Letrozole LEBE (Treatment Period 2, Day 1) until Day 197
Terminal phase elimination rate constant
tmax
时间窗: Following single IM administration of Letrozole LEBE (Treatment Period 2, Day 1) until Day 197
Time to maximum observed concentration
Cmax
时间窗: Following single IM administration of Letrozole LEBE (Treatment Period 2, Day 1) until Day 197
Maximum observed plasma concentration after Letrozole LEBE administration
tlag
时间窗: Following single IM administration of Letrozole LEBE (Treatment Period 2, Day 1) until Day 197
Lag time before observation of quantifiable concentrations in plasma.
Clast
时间窗: Following single IM administration of Letrozole LEBE (Treatment Period 2, Day 1) until Day 197
Last observed plasma concentration after Letrozole LEBE administration
t1/2
时间窗: Following single IM administration of Letrozole LEBE (Treatment Period 2, Day 1) until Day 197
Terminal elimination half life.
AUC∞
时间窗: Following single IM administration of Letrozole LEBE (Treatment Period 2, Day 1) until Day 197
Area under the concentration time curve from time zero extrapolated to infinity.
AUClast
时间窗: Following single IM administration of Letrozole LEBE (Treatment Period 2, Day 1) until Day 197
Area under the concentration time curve from time zero up to the last quantifiable concentration.
次要结局
- SE1(Following single IM administration of Letrozole LEBE (Treatment Period 2, Day 1) until Day 197)
- E2(Following single IM administration of Letrozole LEBE (Treatment Period 2, Day 1) until Day 197)
- E1(Following single IM administration of Letrozole LEBE (Treatment Period 2, Day 1) until Day 197)
- Cav(Following multiple oral administration of Femara (Treatment Period 1, Day 14))
- Cmax,ss(Following multiple oral administration of Femara (Treatment Period 1, Day 14))
- tmax(Following multiple oral administration of Femara (Treatment Period 1, Day 14))
- t1/2(Following multiple oral administration of Femara (Treatment Period 1, Day 14))
- AUCτ(Following multiple oral administration of Femara (Treatment Period 1, Day 14))
- λz(Following multiple oral administration of Femara (Treatment Period 1, Day 14))
- Cmin, ss(Following multiple oral administration of Femara (Treatment Period 1, Day 14))