The Effects of Denosumab on the Pharmacokinetics of Etanercept in Postmenopausal Women With Low Bone Mineral Density and Rheumatoid Arthritis
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Amgen
- 入组人数
- 19
- 试验地点
- 1
- 主要终点
- Maximum Observed Serum Concentration (Cmax) of Etanercept
研究概览
简要总结
The primary objective of the study was to characterize the effects of a single dose of denosumab on the pharmacokinetics (PK) of etanercept in postmenopausal women with low bone mineral density (BMD) and rheumatoid arthritis based on area under the serum concentration-time curve (AUC) and maximum observed serum concentration (Cmax).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 45 Years 至 80 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Postmenopausal women (postmenopausal is defined as no vaginal bleeding or spotting for at least 12 months)
- •Low bone mineral density (BMD) as determined by screening BMD T-scores of the lumbar spine (L1 to L4), or total evaluable vertebrae (if fewer than L1 to L4), or total hip ≤ -1.0
- •Receiving a 50 mg dose of etanercept once weekly ≥ 6 months prior to screening and expected to continue etanercept treatment at this dose and frequency through end of study (EOS)
- •If currently taking methotrexate (MTX), receiving a stable dose (7.5 to 20 mg/week) of MTX ≥ 8 weeks prior to screening
- •Willing and able to take ≥ 1,000 mg elemental calcium and ≥ 400 IU vitamin D daily upon enrollment
排除标准
- •Type 1 diabetes; OR poorly controlled Type 2 diabetes (hemoglobin A1c (HbA1c) > 8.0% at screening; HbA1c ≤ 8.0% within 6 months of screening is acceptable if supporting laboratory documentation is available)
- •History of heart failure, coronary artery bypass graft, or cardiac arrhythmia; OR history of acute coronary syndrome
- •Comorbid autoimmune disease, demyelinating disease, or hematologic abnormalities
- •History of joint replacement in hand and/or wrist; OR history of fused joint in hand and/or wrist
- •Prior history or current evidence of osteonecrosis/osteomyelitis of the jaw; OR active dental or jaw condition that requires oral surgery, or non-healed dental/oral surgery; OR planned invasive dental procedure(s) during the course of the study
- •Previous exposure to denosumab
研究组 & 干预措施
Etanercept + Denosumab
Participants received etanercept 50 mg subcutaneously once weekly for 25 weeks. On study day 8, participants were administered a single 60 mg subcutaneous injection of denosumab.
干预措施: Etanercept (Drug)
Etanercept + Denosumab
Participants received etanercept 50 mg subcutaneously once weekly for 25 weeks. On study day 8, participants were administered a single 60 mg subcutaneous injection of denosumab.
干预措施: Denosumab (Drug)
结局指标
主要结局
Maximum Observed Serum Concentration (Cmax) of Etanercept
时间窗: Day 1 and day 22; at each time point samples were taken predose and 2, 3, 4, 5, 6 and 8 days postdose.
Area Under the Serum Concentration-time Curve From 0 to 168 Hours (AUC0-168) for Etanercept
时间窗: Day 1 and day 22; at each time point samples were taken predose and 2, 3, 4, 5, 6 and 8 days postdose.
The AUC0-168 of etanercept was measured when administered alone (assessed from day 1) and after administration with denosumab (assessed from day 22, 14 days after denosumab dosing, close to the time of the maximum observed denosumab serum concentration and corresponding to a time approximately 1 week after maximal pharmacodynamic (PD) effects of denosumab are attained).
次要结局
- Time to Maximum Serum Concentration (Tmax) of Etanercept(Day 1 and day 22; at each time point samples were taken predose and 2, 3, 4, 5, 6 and 8 days postdose.)
- Serum Denosumab Concentration(Prior to etanercept and denosumab dose administrations, as applicable, on days 8, 22, and 29)
- Percent Change From Baseline in Serum C-telopeptide (sCTx) Concentrations(Baseline (Day 8) and Days 22, 29, 85, and 176)