A Randomized, Double-blind, Three-arm, Parallel-group, Single-dose Study to Compare the Pharmacokinetics, Pharmacodynamics, Safety, Tolerability, and Immunogenicity of Denosumab (ENZ215, EU-sourced Prolia®, and US-sourced Prolia®) in Healthy Adult Male Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 207
- 试验地点
- 2
- 主要终点
- Maximum Observed Drug Concentration (Cmax) of ENZ215 and EU- and US-sourced Prolia®
研究概览
简要总结
This is a randomized, double-blind, three-arm, parallel-group, single-dose study to demonstrate bioequivalence of ENZ215 and EU- and US-sourced Prolia after a single 60-mg dose administered subcutaneously in healthy adult male volunteers.
详细描述
Approximately 207 subjects will be enrolled into 3 groups (69 in each group) in parallel. The subjects may be enrolled in multiple groups at the site. All eligible subjects will be assigned to one of the three treatment groups in 1:1:1 ratio i.e. ENZ215 or US-sourced Prolia® or EU-sourced Prolia® to enter into the study period of 39 weeks. The study duration will be approximately 16 months (i.e. 6 months of recruitment period, 4 weeks of screening period and approximately 39 weeks (270 days) of study period).
Each subject will be required to visit the site for a total of 20 visits: visit 1 - screening visit, visit 2 - day 0 to day 2, visit 3 - day 3, visit 4 - day 4, visit 5 - day 5, visit 6 - day 6, visit 7 - day 8, visit 8 - day 10, visit 9 - day 12, visit 10 - day 16, visit 11 - day 21, visit 12 - day 28 (week 4), visit 13 - day 42 (week 6), visit 14 - day 63 (week 9), visit 15 - day 90 (week 13), visit 16 - day 119 (week 17), visit 17 - day 147 (week 21), visit 18 - day 180 (week 26), visit 19 day - 224 (week 32), and visit 20 - day 270 (week 39). A window period of ±1 day is allowed for visit 12 (day 28), window period of ±3 days are allowed from day 42 (week 6) to day 180 (week 26), A window period of ±5 days are allowed from day 224 (week 32) to day 270 (week 39).
End of Study Assessment will be performed on day 270 (week 39) or at the time of early discontinuation of the subject.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 28 Years 至 55 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
ENZ215
ENZ215 Injection:- 60 mg Denosumab (ENZ215) will be administered subcutaneously on day 1.
干预措施: ENZ215 (Biological)
EU Sourced Prolia
EU sourced Prolia Injection:- 60 mg Denosumab (EU sourced Prolia) will be administered subcutaneously on day 1.
干预措施: EU Sourced Prolia (Biological)
US Sourced Prolia
US sourced Prolia Injection:- 60 mg Denosumab (US sourced Prolia) will be administered subcutaneously on day 1.
干预措施: US Sourced Prolia (Biological)
结局指标
主要结局
Maximum Observed Drug Concentration (Cmax) of ENZ215 and EU- and US-sourced Prolia®
时间窗: 270 days
A total of twenty four blood PK samples of 2.5 mL each were collected from each subject in the study. Pre-dose sample were collected within 30 minutes prior to IP administration. Post-dose samples up to Day 2 were collected within ± 10 minutes, within ± 2 hours from Day 3 to Day 21, within ± 1 day on Day 28, within ± 3 days from Day 42 to Day 180 and within ±5 days from Day 224 to Day 270. Serum concentrations of denosumab were measured at central laboratory by a validated analytical method.
Area Under the Drug Concentration-time Curve From Day 0 to Day 270 (AUC0-t) of ENZ215, EU- and US-sourced Prolia®. and EU- and US-sourced Prolia®
时间窗: 270 days
A total of twenty four blood PK samples of 2.5 mL each were collected from each subject in the study. Pre-dose sample were collected within 30 minutes prior to IP administration. Post-dose samples up to Day 2 were collected within ± 10 minutes, within ± 2 hours from Day 3 to Day 21, within ± 1 day on Day 28, within ± 3 days from Day 42 to Day 180 and within ±5 days from Day 224 to Day 270. Serum concentrations of denosumab were measured at central laboratory by a validated analytical method.
Area Under the Drug Concentration-time Curve From Time 0 to Infinity (AUC0-inf) of ENZ215, EU- and US-sourced Prolia®. and EU- and US-sourced Prolia®
时间窗: 270 days
A total of twenty four blood PK samples of 2.5 mL each were collected from each subject in the study. Pre-dose sample were collected within 30 minutes prior to IP administration. Post-dose samples up to Day 2 were collected within ± 10 minutes, within ± 2 hours from Day 3 to Day 21, within ± 1 day on Day 28, within ± 3 days from Day 42 to Day 180 and within ±5 days from Day 224 to Day 270. Serum concentrations of denosumab were measured at central laboratory by a validated analytical method.
次要结局
- Partial Area Under the Drug Concentration-time Curve From Time 0 (Pre-dose) to Day 28(28 days)
- Time to Reach Cmax (Tmax)(270 days)
- Terminal Elimination Half-life (t1/2)(270 days)
- Apparent Systemic Clearance (CL/F)(270 days)
- Area Under the Effect Curve (AUEC) From Time 0 to Day 270 for Serum CTX-1 Percent Inhibition Percent Inhibition(270 days)