A Phase IIb, Randomized, Placebo-Controlled, Dose-Ranging Study of MK-5442 in the Treatment of Postmenopausal Women With Osteoporosis
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 383
- 主要终点
- Least Squares (LS) Mean Percent Change From Baseline to Month 6 in Lumbar Spine Areal Bone Mineral Density (aBMD)
研究概览
简要总结
The purpose of this study was to identify an appropriate dose of
MK-5442 that produced an osteoanabolic effect without causing hypercalcemia in postmenopausal women with osteoporosis.
详细描述
Amendment 4 of the protocol changed the duration of the study from 2 years to 6 months.
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
- 45 Years 至 85 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Postmenopausal for at least 5 years
- •No history of fragility fracture, unless participant is not willing to take marketed osteoporosis therapy or is not a candidate for marketed osteoporosis therapy
- •Agrees not to use medications for osteoporosis except medications associated with the study
- •Areal bone mineral density (BMD) T-score <-2.5 at one or more of the following 4 BMD sites: total hip, femoral neck, trochanter, or lumbar spine and is ≥ -3.5 at all 4 BMD sites. Participants unwilling to take or ineligible for marketed osteoporosis therapy may have one or more areal BMD T-scores of < -3.5
排除标准
- •Unable to undergo dual-energy X-ray absorptiometry (DXA) scan due to obesity (ie, weight >250 lbs)
- •Use of oral bisphosphonates in the 6 months prior to study screening, for more than 3 months in the past 2 years, or lifetime use of more than 6 months
- •Use of intravenous bisphosphonates, strontium, or growth hormone at any time
- •Use of phenytoin or heparin within 2 weeks prior to Visit 1; use of raloxifene within 6 months prior to Visit 1
- •Use of pioglitazone or rosiglitazone at study screening
- •Use of estrogen ± progestin, in any form other than vaginal or topical application, for 6 months prior to Study Visit 1
- •Prior total thyroidectomy
- •Human immunodeficiency virus (HIV)- positive or acquired immune deficiency syndrome (AIDS)-related illness
- •History of malignant cancer within 5 years of study screening, except for certain skin or cervical cancers
- •History of Paget's disease and/or kidney stones
- •An active user of any illicit drug
- •History of or active alcohol abuse
- •Participated in an investigational drug study within the past 30 days
研究组 & 干预措施
MK-5442 2.5 mg
Following a 2-week open-label placebo run-in, participants received a daily oral dose of 2.5 mg of MK-5442 for a duration of at least 6 months.
干预措施: MK-5442 (Drug)
MK-5442 2.5 mg
Following a 2-week open-label placebo run-in, participants received a daily oral dose of 2.5 mg of MK-5442 for a duration of at least 6 months.
干预措施: Placebo (Drug)
MK-5442 2.5 mg
Following a 2-week open-label placebo run-in, participants received a daily oral dose of 2.5 mg of MK-5442 for a duration of at least 6 months.
干预措施: Vitamin D3 (Dietary Supplement)
MK-5442 2.5 mg
Following a 2-week open-label placebo run-in, participants received a daily oral dose of 2.5 mg of MK-5442 for a duration of at least 6 months.
干预措施: Calcium carbonate (Dietary Supplement)
MK-5442 5 mg
Following a 2-week open-label placebo run-in, participants received a daily oral dose of 5 mg of MK-5442 for a duration of at least 6 months.
干预措施: MK-5442 (Drug)
MK-5442 5 mg
Following a 2-week open-label placebo run-in, participants received a daily oral dose of 5 mg of MK-5442 for a duration of at least 6 months.
干预措施: Placebo (Drug)
MK-5442 5 mg
Following a 2-week open-label placebo run-in, participants received a daily oral dose of 5 mg of MK-5442 for a duration of at least 6 months.
干预措施: Vitamin D3 (Dietary Supplement)
MK-5442 5 mg
Following a 2-week open-label placebo run-in, participants received a daily oral dose of 5 mg of MK-5442 for a duration of at least 6 months.
干预措施: Calcium carbonate (Dietary Supplement)
MK-5442 7.5 mg
Following a 2-week open-label placebo run-in, participants received a daily oral dose of 7.5 mg of MK-5442 for a duration of at least 6 months.
干预措施: MK-5442 (Drug)
MK-5442 7.5 mg
Following a 2-week open-label placebo run-in, participants received a daily oral dose of 7.5 mg of MK-5442 for a duration of at least 6 months.
干预措施: Placebo (Drug)
MK-5442 7.5 mg
Following a 2-week open-label placebo run-in, participants received a daily oral dose of 7.5 mg of MK-5442 for a duration of at least 6 months.
干预措施: Vitamin D3 (Dietary Supplement)
MK-5442 7.5 mg
Following a 2-week open-label placebo run-in, participants received a daily oral dose of 7.5 mg of MK-5442 for a duration of at least 6 months.
干预措施: Calcium carbonate (Dietary Supplement)
MK-5442 10 mg
Following a 2-week open-label placebo run-in, participants received a daily oral dose of 10 mg of MK-5442 for a duration of at least 6 months.
干预措施: MK-5442 (Drug)
MK-5442 10 mg
Following a 2-week open-label placebo run-in, participants received a daily oral dose of 10 mg of MK-5442 for a duration of at least 6 months.
干预措施: Placebo (Drug)
MK-5442 10 mg
Following a 2-week open-label placebo run-in, participants received a daily oral dose of 10 mg of MK-5442 for a duration of at least 6 months.
干预措施: Vitamin D3 (Dietary Supplement)
MK-5442 10 mg
Following a 2-week open-label placebo run-in, participants received a daily oral dose of 10 mg of MK-5442 for a duration of at least 6 months.
干预措施: Calcium carbonate (Dietary Supplement)
MK-5442 15 mg
Following a 2-week open-label placebo run-in, participants received a daily oral dose of 15 mg of MK-5442 for a duration of at least 6 months.
干预措施: MK-5442 (Drug)
MK-5442 15 mg
Following a 2-week open-label placebo run-in, participants received a daily oral dose of 15 mg of MK-5442 for a duration of at least 6 months.
干预措施: Placebo (Drug)
MK-5442 15 mg
Following a 2-week open-label placebo run-in, participants received a daily oral dose of 15 mg of MK-5442 for a duration of at least 6 months.
干预措施: Vitamin D3 (Dietary Supplement)
MK-5442 15 mg
Following a 2-week open-label placebo run-in, participants received a daily oral dose of 15 mg of MK-5442 for a duration of at least 6 months.
干预措施: Calcium carbonate (Dietary Supplement)
Placebo
Following a 2-week open-label placebo run-in, participants received a daily oral dose of placebo dose-matched to MK-5442 for a duration of at least 6 months.
干预措施: Placebo (Drug)
Placebo
Following a 2-week open-label placebo run-in, participants received a daily oral dose of placebo dose-matched to MK-5442 for a duration of at least 6 months.
干预措施: Vitamin D3 (Dietary Supplement)
Placebo
Following a 2-week open-label placebo run-in, participants received a daily oral dose of placebo dose-matched to MK-5442 for a duration of at least 6 months.
干预措施: Calcium carbonate (Dietary Supplement)
结局指标
主要结局
Least Squares (LS) Mean Percent Change From Baseline to Month 6 in Lumbar Spine Areal Bone Mineral Density (aBMD)
时间窗: Baseline (BL) and Month 6
Dual Energy X-ray Absorptiometry (DXA) was used to assess and measure aBMD of the lumbar spine. Areal BMD was measured as "areal" density using units of gram (gm) of tissue /centimeter of tissue squared (cm\^2).
Percentage of Participants With Total Serum Calcium Levels Outside the Pre-defined Limits of Change
时间窗: Baseline through Month 6
Normal serum calcium level is 8-10 mg/dL (2-2.5 mmol/L) with some interlaboratory variation in the reference range, and hypercalcemia is defined as a serum calcium level greater than 10.5 mg/dL (\>2.5 mmol/L). Based on these references, ≥10.6 mg/dL was predefined in this study as the cut-off for the normal limits of change. Participants with calcium levels ≥10.6 mg/dL were considered as having a "Tier 1" safety event.
Percentage of Participants With Albumin-Corrected Calcium Levels Outside the Pre-defined Limits of Change
时间窗: Baseline through Month 6
Albumin-Corrected Calcium = (\[4 - plasma albumin in g/dL\] × 0.8 + serum calcium). ≥10.6 mg/dL was predefined in this study as the cut-off for the normal limits of change. Participants with albumin-corrected calcium levels ≥10.6 mg/dL were considered as having a "Tier 1" safety event.
Percentage of Participants With Kidney Stones
时间窗: Baseline through Month 6
Evidence of kidney stone(s) was considered an event of interest and was prespecified as a "Tier 1" safety event.
Percentage of Participants With Bone Neoplasms
时间窗: Baseline through Month 6
Evidence of bone neoplasm(s) was considered an event of interest and was prespecified as a "Tier 1" safety event.
次要结局
- LS Mean Percent Change From Baseline to Month 6 in Distal One-third Forearm Areal BMD(Baseline and Month 6)
- LS Mean Percent Change From Baseline to Month 6 in Trabecular Volumetric BMD of the Hip(Baseline and Month 6)
- LS Mean Percent Change From Baseline to Month 6 in Trochanter aBMD(Baseline and Month 6)
- LS Mean Percent Change From Baseline to Month 6 in Trabecular Volumetric BMD of the Lumbar Spine(Baseline and Month 6)
- LS Mean Percent Change From Baseline to Month 6 in Total Hip aBMD(Baseline and Month 6)
- LS Mean Percent Change From Baseline to Month 6 in Femoral Neck aBMD(Baseline and Month 6)
- LS Mean Percent Change From Baseline to Month 6 in Total Body aBMD(Baseline and Month 6)
- LS Mean Percent Change From Baseline to Month 6 in the Ratio of Urinary N-Telopeptides of Type I Collagen to Creatinine (u-NTx/Cr)(Baseline and Month 6)
- LS Mean Percent Change From Baseline to Month 6 in Serum C-Terminal Telopeptide Collagen I (s-CTx)(Baseline to Month 6)
- LS Mean Percent Change From Baseline to Month 6 in Serum Bone-Specific Alkaline Phosphatase (s-BSAP)(Baseline and Month 6)
- LS Mean Percent Change From Baseline to Month 6 in Serum Procollagen Type I N-Terminal Propeptide (P1NP)(Baseline to Month 6)
- LS Mean Percent Change From Baseline to Month 6 in Serum Osteocalcin(Baseline and Month 6)