A Phase IIb, Randomized, Double-Blind, Placebo- and Active-Controlled, Dose-Range-Finding Study to Evaluate the Effects of MK-5442 on Bone Mineral Density (BMD) in the Treatment of Osteoporosis in Postmenopausal Women Previously Treated With an Oral Bisphosphonate
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 526
- 主要终点
- Number of Participants With Predefined Tier 1 Adverse Events
研究概览
简要总结
This study seeks to demonstrate that additional gain in bone mineral density (BMD) can be achieved by switching to MK-5442 from an oral bisphosphonate in participants who have been receiving oral bisphosphonate therapy for at least 3 years.
详细描述
The study was originally planned for a duration of 2 years and included efficacy analysis of a 15 mg MK-5442 treatment arm. Amendment 1 of the protocol eliminated the 2nd year of the study as well the 15-mg arm. Enrollment into the 15-mg MK-5442 arm was stopped as a result of the amendment and all participants who had been randomly assigned to the MK-5442 15-mg treatment arm were discontinued from the study.
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
- •Taking oral bisphosphonate treatment for osteoporosis for at least 3 of the past 4 years. At present, and for the past 12 months, treated with alendronate
- •Bone Mineral Density (BMD) T-score that is ≤ -1.5 at one or more of the following anatomic sites; lumbar spine, femoral neck, trochanter, and total hip, AND a BMD T-score at all of these sites that is ≥ -4.0, AND a history of at least one fragility fracture, OR, a BMD T-score that is ≤ -2.5 at one or more of the following anatomic sites; lumbar spine, femoral neck, trochanter, and total hip, AND a BMD T-score at all of these sites that is ≥ -4.0
- •Postmenopausal for at least 5 years
排除标准
- •Obesity (ie, weight greater than 250 pounds) that prohibits the use of dual-emission X-ray absorptiometry (DXA)
- •Received intravenous (IV) bisphosphonates, fluoride treatment at a dose >1 mg/day for more than 2 weeks, strontium, growth hormone, a cathepsin K (CTSK) inhibitor, or a receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitor at any time in the past
- •Use of oral bisphosphonates other than alendronate in the last 12 months, parathyroid hormone (PTH) in the last 24 months, cyclosporin for more than 2 weeks in the last 6 months, heparin in the last 2 weeks, or anabolic steroids or glucocorticoids for more than 2 weeks in the past 6 months
- •Use of estrogen with or without progestin or a selective estrogen receptor modulator (SERM) in the last 6 months or calcitonin in the last 30 days
- •Has used pioglitazone hydrochloride or rosiglitazone hydrochloride in the last 6 months
- •Taking more than 10,000 International Units (IU) vitamin A daily or more than 5,000 IU vitamin D daily
- •Has had a total thyroidectomy
- •History of Paget's disease
- •Has human immunodeficiency virus (HIV)
- •History of cancer in the last 5 years, except certain skin or cervical cancers
- •History of major upper gastrointestinal (GI) mucosal erosive disease
- •Unable to adhere to dosing instructions for alendronate in regard to fasting and positioning
- •Not ambulatory
研究组 & 干预措施
Placebo
Participants received either matching placebo to alendronate (administered orally, once-weekly) or matching placebo to MK-5442 (administered orally, once-daily) for 12 months. Participants also received supplemental vitamin D3 and calcium (as needed) during treatment.
干预措施: Placebo to MK-5442 (Drug)
Placebo
Participants received either matching placebo to alendronate (administered orally, once-weekly) or matching placebo to MK-5442 (administered orally, once-daily) for 12 months. Participants also received supplemental vitamin D3 and calcium (as needed) during treatment.
干预措施: Vitamin D3 (Drug)
Placebo
Participants received either matching placebo to alendronate (administered orally, once-weekly) or matching placebo to MK-5442 (administered orally, once-daily) for 12 months. Participants also received supplemental vitamin D3 and calcium (as needed) during treatment.
干预措施: Calcium carbonate (Drug)
Placebo
Participants received either matching placebo to alendronate (administered orally, once-weekly) or matching placebo to MK-5442 (administered orally, once-daily) for 12 months. Participants also received supplemental vitamin D3 and calcium (as needed) during treatment.
干预措施: Placebo to Alendronate (Drug)
MK-5442 5 mg
Participants received 5 mg of MK-5442 (orally, once-daily) plus matching placebo to alendronate (administered orally, once-weekly) for 12 months. Participants also received supplemental vitamin D3 and calcium (as needed) during treatment.
干预措施: MK-5442 (Drug)
MK-5442 5 mg
Participants received 5 mg of MK-5442 (orally, once-daily) plus matching placebo to alendronate (administered orally, once-weekly) for 12 months. Participants also received supplemental vitamin D3 and calcium (as needed) during treatment.
干预措施: Vitamin D3 (Drug)
MK-5442 5 mg
Participants received 5 mg of MK-5442 (orally, once-daily) plus matching placebo to alendronate (administered orally, once-weekly) for 12 months. Participants also received supplemental vitamin D3 and calcium (as needed) during treatment.
干预措施: Calcium carbonate (Drug)
MK-5442 5 mg
Participants received 5 mg of MK-5442 (orally, once-daily) plus matching placebo to alendronate (administered orally, once-weekly) for 12 months. Participants also received supplemental vitamin D3 and calcium (as needed) during treatment.
干预措施: Placebo to Alendronate (Drug)
MK-5442 7.5 mg
Participants received 7.5 mg of MK-5442 (orally, once-daily) plus matching placebo to alendronate (administered orally, once-weekly) for 12 months. Participants also received supplemental vitamin D3 and calcium (as needed) during treatment.
干预措施: MK-5442 (Drug)
MK-5442 7.5 mg
Participants received 7.5 mg of MK-5442 (orally, once-daily) plus matching placebo to alendronate (administered orally, once-weekly) for 12 months. Participants also received supplemental vitamin D3 and calcium (as needed) during treatment.
干预措施: Vitamin D3 (Drug)
MK-5442 7.5 mg
Participants received 7.5 mg of MK-5442 (orally, once-daily) plus matching placebo to alendronate (administered orally, once-weekly) for 12 months. Participants also received supplemental vitamin D3 and calcium (as needed) during treatment.
干预措施: Calcium carbonate (Drug)
MK-5442 7.5 mg
Participants received 7.5 mg of MK-5442 (orally, once-daily) plus matching placebo to alendronate (administered orally, once-weekly) for 12 months. Participants also received supplemental vitamin D3 and calcium (as needed) during treatment.
干预措施: Placebo to Alendronate (Drug)
MK-5442 10 mg
Participants received 10 mg of MK-5442 (orally, once-daily) plus matching placebo to alendronate (administered orally, once-weekly) for 12 months. Participants also received supplemental vitamin D3 and calcium (as needed) during treatment.
干预措施: MK-5442 (Drug)
MK-5442 10 mg
Participants received 10 mg of MK-5442 (orally, once-daily) plus matching placebo to alendronate (administered orally, once-weekly) for 12 months. Participants also received supplemental vitamin D3 and calcium (as needed) during treatment.
干预措施: Vitamin D3 (Drug)
MK-5442 10 mg
Participants received 10 mg of MK-5442 (orally, once-daily) plus matching placebo to alendronate (administered orally, once-weekly) for 12 months. Participants also received supplemental vitamin D3 and calcium (as needed) during treatment.
干预措施: Calcium carbonate (Drug)
MK-5442 10 mg
Participants received 10 mg of MK-5442 (orally, once-daily) plus matching placebo to alendronate (administered orally, once-weekly) for 12 months. Participants also received supplemental vitamin D3 and calcium (as needed) during treatment.
干预措施: Placebo to Alendronate (Drug)
MK-5442 15 mg
Participants received 15 mg of MK-5442 (orally, once-daily) plus matching placebo to alendronate (administered orally, once-weekly) for 12 months. Participants also received supplemental vitamin D3 and calcium (as needed) during treatment.
干预措施: MK-5442 (Drug)
MK-5442 15 mg
Participants received 15 mg of MK-5442 (orally, once-daily) plus matching placebo to alendronate (administered orally, once-weekly) for 12 months. Participants also received supplemental vitamin D3 and calcium (as needed) during treatment.
干预措施: Vitamin D3 (Drug)
MK-5442 15 mg
Participants received 15 mg of MK-5442 (orally, once-daily) plus matching placebo to alendronate (administered orally, once-weekly) for 12 months. Participants also received supplemental vitamin D3 and calcium (as needed) during treatment.
干预措施: Calcium carbonate (Drug)
MK-5442 15 mg
Participants received 15 mg of MK-5442 (orally, once-daily) plus matching placebo to alendronate (administered orally, once-weekly) for 12 months. Participants also received supplemental vitamin D3 and calcium (as needed) during treatment.
干预措施: Placebo to Alendronate (Drug)
Alendronate 70 mg
Participants received 70 mg alendronate (orally, once-weekly) plus matching placebo to MK-5442 (administered orally, once-daily) for 12 months. Participants also received supplemental vitamin D3 and calcium (as needed) during treatment.
干预措施: Placebo to MK-5442 (Drug)
Alendronate 70 mg
Participants received 70 mg alendronate (orally, once-weekly) plus matching placebo to MK-5442 (administered orally, once-daily) for 12 months. Participants also received supplemental vitamin D3 and calcium (as needed) during treatment.
干预措施: Alendronate Sodium (Drug)
Alendronate 70 mg
Participants received 70 mg alendronate (orally, once-weekly) plus matching placebo to MK-5442 (administered orally, once-daily) for 12 months. Participants also received supplemental vitamin D3 and calcium (as needed) during treatment.
干预措施: Vitamin D3 (Drug)
Alendronate 70 mg
Participants received 70 mg alendronate (orally, once-weekly) plus matching placebo to MK-5442 (administered orally, once-daily) for 12 months. Participants also received supplemental vitamin D3 and calcium (as needed) during treatment.
干预措施: Calcium carbonate (Drug)
结局指标
主要结局
Number of Participants With Predefined Tier 1 Adverse Events
时间窗: Baseline through Month 12
Osteonecrosis of the jaw (ONJ), kidney stones, and bone neoplasms were predefined Tier-1 AEs in the study (an AE of special interest identified a priori that could be used for inferential testing for statistical significance for between-group comparisons).
Least Squares Mean Percent Change From Baseline To Month 12 in Lumbar Spine Areal Bone Mineral Density (BMD)
时间窗: Baseline and Month 12
Areal bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry (DXA) scanning technology. Scanning is performed with two X-ray beams with different energy levels which are aimed at the participant's bones. When soft tissue absorption is subtracted out, the BMD is determined from the absorption of each beam by bone. BMD = BMC / W, where BMD = bone mineral density in g/cm\^2, BMC = bone mineral content in g/cm, and W = width at the scanned line in cm
Number of Participants With Trough Albumin-Corrected Calcium Level Exceeding Predefined Limits At Least Once
时间窗: Baseline through Month 12
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 at least one albumin-corrected calcium level value ≥10.6 mg/dL were considered as having a "Tier 1" AE (an AE of special interest identified a priori that could be used for inferential testing for statistical significance for between-group comparisons).
Number of Participants With Trough Serum Calcium Level Exceeding Predefined Limits At Least Once
时间窗: Baseline through Month 12
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 at least a one calcium level value ≥10.6 mg/dL were considered as having a "Tier 1" adverse event (AE). A Tier 1 AE was an AE of special interest identified a priori that could be used for inferential testing for statistical significance for between-group comparisons.
次要结局
- Least Squares Mean Percent Change From Baseline to Month 12 in Trochanter Areal BMD(Baseline and Month 12)
- Least Squares Mean Percent Change From Baseline to Month 12 in Total Hip Areal BMD(Baseline and Month 12)
- Least Squares Mean Percent Change From Baseline to Month 12 in Femoral Neck Areal BMD(Baseline and Month 12)
- Least Squares Mean Percent Change From Baseline to Month 12 in Total Body Areal BMD(Baseline and Month 12)
- Least Squares Mean Percent Change From Baseline to Month 12 in 1/3 Distal Forearm Areal BMD(Baseline and Month 12)
- Least Squares Mean Percent Change From Baseline to Month 12 in Trabecular Volumetric BMD (vBMD) of the Lumbar Spine(Baseline and Month 12)
- Least Squares Mean Percent Change From Baseline to Month 12 in Trabecular Volumetric BMD of the Hip(Baseline and Month 12)
- Least Squares Mean Percent Change From Baseline to Month 12 in Cortical Volumetric BMD of the Lumbar Spine(Baseline and Month 12)
- Least Squares Mean Percent Change From Baseline to Month 12 in Urinary-N Telopeptides of Type 1 Collagen (u-NTx)(Baseline and Month 12)
- Least Squares Mean Percent Change From Baseline to Month 12 in Cortical Volumetric BMD of the Hip(Baseline and Month 12)
- Least Squares Mean Percent Change From Baseline to Month 12 in Serum N-Terminal Propeptide (s-P1NP)(Baseline and Month 12)
- Least Squares Mean Percent Change From Baseline to Month 12 in Serum Osteocalcin(Baseline and Month 12)
- Least Squares Mean Percent Change From Baseline to Month 12 in Serum C-Terminal Propeptide of Type 1 Collagen (s-CTx)(Baseline and Month 12)
- Least Squares Mean Percent Change From Baseline to Month 12 in Serum Bone-Specific Alkaline Phosphatase (s-BSAP)(Baseline and Month 12)