A Randomized, Double-blind, Placebo-controlled, Single-dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 785 in Healthy Postmenopausal Japanese Women
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 31
- 主要终点
- Number of Participants With Adverse Events
研究概览
简要总结
The main purpose of this study is to assess the safety, tolerability and potential immune response to romosozumab following single subcutaneous (SC; injection under the skin) dose administration in healthy postmenopausal Japanese and non-Japanese women.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 45 Years 至 70 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Japanese subjects must be first (4 grandparents, biologic parents and subject born in Japan), second (4 grandparents and biological parents born in Japan) or third (4 grandparents born in Japan) generation Japanese
- •Body mass index ≤ 25 kg/m², inclusive at screening
- •Postmenopausal females defined as 12 continuous months of spontaneous amenorrhea confirmed by a serum follicle-stimulating hormone (FSH) result > 40 mIU/mL, or 6 weeks postsurgical bilateral oophorectomy (with or without hysterectomy) as documented in medical history (verified with an operative note, if available)
排除标准
- •Osteoporosis, as defined by bone mineral density (BMD) T-scores of the lumbar spine (L1-L4) or total evaluable vertebrae (if fewer than L1-L4); or femoral neck ≤ -2.5
- •History of vertebral fracture or fragility fracture of the wrist, humerus, hip or pelvis;
- •Diagnosed with any condition that will affect bone metabolism
研究组 & 干预措施
Romosozumab
Japanese women in cohorts 1, 2, and 4 will receive a single dose of 1, 3, or 5 mg/kg romosozumab. Non-Japanese women in cohort 3 will receive a single dose of 3 mg/kg romosozumab.
干预措施: Romosozumab (Drug)
Placebo
Participants will receive a single dose of placebo.
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Participants With Adverse Events
时间窗: Participants who received a 1 or 3 mg/kg dose (romosozumab or placebo) were followed for 2 months (day 57) after study drug administration and participants who received 5 mg/kg were followed for 3 months (day 85) for safety assessments.
A serious adverse event (SAE) is defined as an adverse event that * is fatal * is life threatening * requires in-patient hospitalization or prolongation of existing hospitalization * results in persistent or significant disability/incapacity * is a congenital anomaly/birth defect * other significant medical hazard. A treatment-related AE is any treatment-emergent AE that per investigator review has a reasonable possibility of being caused by the investigational product.
Number of Participants Who Developed Anti-romosozumab Binding Antibodies
时间窗: Day 29, and end of study (day 57 for participants assigned to 1 or 3 mg/kg romosozumab/placebo or day 85 for participants assigned to 5 mg/kg romosozumab/placebo)
Participants who were negative for anti-romosozumab binding antibodies at baseline with a positive result at any time post-baseline.
Serum Calcium Levels
时间窗: Baseline, days 2, 3, 4, 6, 8, 12, 22, 29, 43, 57, 71, and 85
Serum Intact Parathyroid Hormone (iPTH) Levels
时间窗: Baseline and days 2, 3, 4, 6, 8, 12, 22, 29, 43, 57, 71, and 85
次要结局
- Maximum Percent Change From Baseline in Serum Procollagen Type 1 N-terminal Propeptide (P1NP)(Baseline and days 2, 3, 4, 6, 8, 12, 22, 29, 43, 57, 71, and 85)
- Maximum Percent Change From Baseline in Serum C-telopeptide (CTX)(Baseline and days 2, 3, 4, 6, 8, 12, 22, 29, 43, 57, 71, and 85)
- Percent Change From Baseline in Sclerostin(Baseline and days 12, 29, 43, 57, 71, and 85)
- Time to Maximum Observed Concentration of Romosozumab(Predose, 12 hours postdose, and on days 2, 3, 4, 6, 8, 12, 22, 29, 43, and 57, and days 71 and 85 for participants assigned tp 5 mg/kg romosozumab/placebo.)
- Maximum Observed Concentration of Romosozumab(Predose, 12 hours postdose, and on days 2, 3, 4, 6, 8, 12, 22, 29, 43, and 57, and days 71 and 85 for participants assigned tp 5 mg/kg romosozumab/placebo.)
- Area Under the Serum Concentration-time Curve From Time 0 to the Last Quantifiable Concentration (AUClast) of Romosozumab(Predose, 12 hours postdose, and on days 2, 3, 4, 6, 8, 12, 22, 29, 43, and 57, and days 71 and 85 for participants assigned tp 5 mg/kg romosozumab/placebo.)
- Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) for Romosozumab(Predose, 12 hours postdose, and on days 2, 3, 4, 6, 8, 12, 22, 29, 43, and 57, and days 71 and 85 for participants assigned tp 5 mg/kg romosozumab/placebo.)
- Apparent Clearance (CL/F) of Romosozumab(Predose, 12 hours postdose, and on days 2, 3, 4, 6, 8, 12, 22, 29, 43, and 57, and days 71 and 85 for participants assigned tp 5 mg/kg romosozumab/placebo.)
- Half-life Associated With Beta (Plateau) Phase of Elimination (T1/2,β) for Romosozumab(Predose, 12 hours postdose, and on days 2, 3, 4, 6, 8, 12, 22, 29, 43, and 57, and days 71 and 85 for participants assigned tp 5 mg/kg romosozumab/placebo.)
- Half-life Associated With Gamma (Terminal) Phase of Elimination (T1/2,ɣ) for Romosozumab(Predose, 12 hours postdose, and on days 2, 3, 4, 6, 8, 12, 22, 29, 43, and 57, and days 71 and 85 for participants assigned tp 5 mg/kg romosozumab/placebo.)