The Effects of Denosumab on the Pharmacokinetics (PK) of Midazolam, a Cytochrome P450 3A4/P-gp (CYP3A4) Substrate, in Postmenopausal Osteoporotic Women
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 30
- 主要终点
- Estimates of Inter- and Intra-subject Variability for the PK AUC Parameters for Midazolam With Denosumab Group
研究概览
简要总结
This is a multi-center, open-label, drug-drug interaction study in postmenopausal women with osteoporosis.
详细描述
Approximately 27 subjects (Group A: 18; Group B: 9) will receive a 2 mg oral dose of midazolam on day 1 followed by a 24 hour PK collection. Subjects randomized to Group A will receive a single 60 mg subcutaneous (SC) dose of denosumab on day 2 administered in the abdomen. On study day 16, another 2 mg oral dose of midazolam will be administered to all subjects (Groups A and B) followed by a 24 hour PK collection. The primary analysis to determine the effect of denosumab on the PK of midazolam will be based on data from subjects in Group A only.
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
- 45 Years 至 75 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Between 45 to 75 years of age
- •Postmenopausal women
- •Osteoporosis
排除标准
- •Use of any known inhibitors of cytochrome P450 3A4/P-gp (CYP3A4) within 14 days or 5 half lives, whichever is longer; or grapefruit juice or grapefruit containing products within 7 days prior to investigational product administration
- •Use of any known CYP3A4 inducers within 30 days or 5 half-lives, whichever is longer, prior to investigational product administration
- •Use of any herbal medicine with a known impact on CYP3A4 (eg, St. John's wort) within 30 days prior to investigational product administration
- •Current use of medications prescribed for osteoporosis treatment
- •Use of midazolam within 14 days prior to investigational product administration
- •Influenza or other vaccination within 28 days of screening
- •Previous exposure to denosumab
研究组 & 干预措施
Midazolam
All 27 subjects will receive midazolam.
干预措施: Denosumab (Drug)
Denosumab
Eighteen (18) subjects will receive denosumab.
干预措施: Midazolam (Drug)
结局指标
主要结局
Estimates of Inter- and Intra-subject Variability for the PK AUC Parameters for Midazolam With Denosumab Group
时间窗: From day 1 pre-dose to 24 hours post-dose and from day 16 pre-dose to 24 hours post-dose
AUC Subject denotes the inter-subject variability, while AUC Residual denotes the intra-subject variability
Ratio of Pharmcokinetic (PK) Area Under the Concentration Time Curve (AUC) Parameter Estimates Between Day 16 (Midazolam With the Presence of Denosumab) and Day 1 (Midazolam Only)
时间窗: From day 1 pre-dose to 24 hours post-dose and from day 16 pre-dose to 24 hours post-dose
The ratio and confidence interval are calculated based on natural log scale data and converted back to the original scale.
Estimates of Inter- and Intra-subject Variability for PK Maximum Observed Plasma Concentration (Cmax) Parameter for Midazolam With Denosumab Group
时间窗: From day 1 pre-dose to 24 hours post-dose and from day 16 pre-dose to 24 hours post-dose
Cmax Subject denotes the inter-subject variability, while Cmax Residual denotes the intra-subject variability
Ratio of PK Cmax Parameter Estimates Between Day 16 (Midazolam With the Presence of Denosumab) and Day 1 (Midazolam Only)
时间窗: From day 1 pre-dose to 24 hours post-dose and from day 16 pre-dose to 24 hours post-dose
The ratio and confidence interval are calculated based on natural log scale data and converted back to the original scale.
次要结局
- Ratio of PK Cmax Parameter Estimates Between Day 16 (Midazolam Only) and Day 1(Midazolam Only)(From day 1 pre-dose to 24 hours post-dose and from day 16 pre-dose to 24 hours post-dose)
- Estimates of Inter- and Intra-subject Variability for the PK AUC Parameters for Midazolam Only Group(From day 1 pre-dose to 24 hours post-dose and from day 16 pre-dose to 24 hours post-dose)
- Estimates of Inter- and Intra-subject Variability for PK Cmax Parameter for Midazolam Only Group(From day 1 pre-dose to 24 hours post-dose and from day 16 pre-dose to 24 hours post-dose)
- Summary of Serum C-Telopeptide Concentration(Baseline (day 2 pre-dose) to day 16)
- Ratio of PK AUC Parameter Estimates Between Day 16 (Midazolam Only) and Day 1(Midazolam Only)(From day 1 pre-dose to 24 hours post-dose and from day 16 pre-dose to 24 hours post-dose)
- Summary of Serum Denosumab Concentration(Baseline (day 2 pre-dose) to day 16)
- Summary of Percent Change From Baseline to Day 16 for Serum C-Telopeptide Concentration(Baseline (day 2 pre-dose) to day 16)