A Phase 2 Randomized Study of LY2541546 Versus Placebo in Postmenopausal Women With Low Bone Mineral Density: An Evaluation of the Dose Response Relationship Using Bone Mineral Density
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 154
- 试验地点
- 1
- 主要终点
- Change From Baseline to 52 Week Endpoint in Lumbar Spine Bone Mineral Density (BMD)
研究概览
简要总结
The primary objectives of this study include evaluating the dose response of LY2541546 using bone mineral density (BMD) change from baseline as compared to placebo and evaluating the overall safety and tolerability of LY2541546 following multiple subcutaneous administrations in postmenopausal (PMP) women with low BMD. Following the last dose of study drug, participants will be able to participate in a 12 month extension to collect additional safety and efficacy data (no further treatment will be administered during this extension).
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
- •Ambulatory, postmenopausal women, inclusive.
- •Have low bone mineral density (BMD), defined as a T-score or equivalent BMD absolute value (grams/square centimeter [g/cm^2]) for the lumbar spine of between -3.5 and -2.0, inclusive.
- •Without language barrier, reliable, and willing to make themselves available for the duration of the study and to follow study procedures.
- •Willing to take study drug and daily supplements (calcium and Vitamin D).
- •Normal laboratory tests or laboratory test results determined not clinically significant by the investigator. Serum phosphate and serum calcium must be within normal limits, and platelet level greater than 100,000 cubic millimeters (mm^3).
排除标准
- •Have received treatment with any of the following medications more recently than 3 months prior to screening Androgen, Calcitonin, Estrogen (including over the counter preparations known to have estrogenic activity), Progestin (including over the counter preparations known to have progestogenic activity), selective estrogen receptor modulators (SERMs) (Raloxifene, Tamoxifen, Toremifene, Clomiphene), or Tibolone.
- •Have previously used or currently use denosumab, parathyroid hormone (PTH) and/or PTH analogs, strontium ranelate, or parenteral formulations of bisphosphonates.
- •Have received treatment with any oral bisphosphonate within the last year.
- •Have received therapeutic doses of systemic corticosteroids for more than one month during the 6 months prior to screening.
- •Have received therapeutic doses of fluorides (20 milligrams per day) for more than 3 months during the last 3 years, or for more than a total of 2 years, or any within the last 6 months.
- •Have severe Vitamin D deficiency defined as 25-hydroxyvitamin D less than <9.2 nanograms per milliliter (ng/mL) [23 nanomoles per liter (nmol/L)] at screening. If the serum 25-hydroxy-vitamin D level at screening is less than or equal to 9.2 ng/mL and <20 ng/mL, participants will receive a loading dose of Vitamin D (at a dose of approximately 100,000 international units (IU) given orally) prior to enrollment.
- •Have any known bone disorder other than low BMD or osteoporosis.
- •Have a history of osteoporotic fractures, including known prevalent vertebral fracture or evidence of prevalent vertebral fracture on screening spine X-ray or dual-energy x-ray absorptiometry (DXA), or are considered to be at high risk for fracture.
- •Presence of any abnormality (such as artifacts or osteophytes) that would confound DXA evaluation of lumbar vertebrae in the L-1 through L-4 region.
- •Have a history of Bell's palsy, other cranial nerve disorders, or have a history of Temporomandibular Joint and Muscle Disorders (TMJDs).
- •Have any history of cancer within the previous 5 years, except for excised superficial lesions such as basal cell carcinoma and squamous cell carcinoma of the skin.
- •Have history or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of constituting a risk when taking the study medication or of interfering with the interpretation of data.
- •Have acute or chronic liver disease ([bilirubin >34 micromoles per liter (µmol/L) or >2.0 milligrams per deciliter (mg/dL), alanine transaminase [ALT/SGPT] >100 units per liter (U/L), or alkaline phosphatase >300 U/L)].
- •Have impaired kidney function serum creatinine >135 µmol/L or >2.0 mg/dL.
- •Have known allergy to LY2541546, any of diluents or excipients of LY2541546, or significant allergy to any other monoclonal antibody.
- •History of excessive consumption of alcohol or abuse of drugs within the last year.
- •Have poor medical condition or psychiatric risks for treatment with an investigational drug.
研究组 & 干预措施
180 mg LY2541546 Q4W + Placebo
LY2541546: 180 milligrams (mg) administered subcutaneously every 4 weeks (Q4W) for 52 weeks.
Placebo: administered subcutaneously every alternate 2 weeks from the LY2541546 dose for 52 weeks.
干预措施: LY2541546 (Drug)
180 mg LY2541546 Q4W + Placebo
LY2541546: 180 milligrams (mg) administered subcutaneously every 4 weeks (Q4W) for 52 weeks.
Placebo: administered subcutaneously every alternate 2 weeks from the LY2541546 dose for 52 weeks.
干预措施: Placebo (Drug)
180 mg LY2541546 Q2W
LY2541546: 180 milligrams (mg) administered subcutaneously every 2 weeks (Q2W) for 52 weeks.
干预措施: LY2541546 (Drug)
270 mg LY2541546 Q2W
LY2541546: 270 milligrams (mg) LY2541546 administered subcutaneously every 2 weeks (Q2W) for 52 weeks.
干预措施: LY2541546 (Drug)
270 mg LY2541546 Q12W + Placebo
LY2541546: 270 milligrams (mg) administered subcutaneously every 12 weeks (Q12W) for 52 weeks.
Placebo: administered subcutaneously every alternate 2 weeks from the LY2541546 dose for 52 weeks.
干预措施: LY2541546 (Drug)
270 mg LY2541546 Q12W + Placebo
LY2541546: 270 milligrams (mg) administered subcutaneously every 12 weeks (Q12W) for 52 weeks.
Placebo: administered subcutaneously every alternate 2 weeks from the LY2541546 dose for 52 weeks.
干预措施: Placebo (Drug)
Placebo Comparator Q2W
Placebo: administered subcutaneously every 2 weeks (Q2W) for 52 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline to 52 Week Endpoint in Lumbar Spine Bone Mineral Density (BMD)
时间窗: Baseline, 52 weeks
Lumbar spine bone mineral density (BMD) measured by dual energy x-ray absorptiometry (DXA). Least squares (LS) mean values were determined using a mixed-effects model repeated-measures (MMRM) analysis of covariance. Factors in the model included treatment, time and the interaction of treatment by time as fixed effects, and baseline lumbar spine BMD as a covariate.
次要结局
- Change From Baseline to 12, 24, and 64 Weeks in Lumbar Spine Bone Mineral Density (BMD)(Baseline, 12 weeks and 24 weeks and 64 weeks)
- Change From Baseline to 52 Week Endpoint in Bone-specific Alkaline Phosphatase (BSAP)(Baseline, 52 weeks)
- Change From Baseline to 24, 52, and 64 Weeks in Proximal Femur Bone Mineral Density (BMD)(Baseline, 24 weeks and 52 weeks and 64 weeks)
- Change From Baseline to 52 Week Endpoint in Serum Type I Collagen Fragment (CTx)(Baseline, 52 weeks)
- Change From Baseline to 52 Week Endpoint in Osteocalcin(Baseline, 52 weeks)
- Change From Baseline to 52 Week Endpoint in Serum N-terminal Extension Propeptide of Type I Collagen (P1NP)(Baseline, 52 weeks)
- Change From Baseline to 52 Week Endpoint in Wrist Bone Mineral Density (BMD)(Baseline, 52 weeks)