A Study to Evaluate the Effects of Calcium Supplementation on the Efficacy and Safety of Recombinant Human Parathyroid Hormone (ALX1-11) in Postmenopausal Women With Osteoporosis (CAP Study)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Shire
- 入组人数
- 374
- 试验地点
- 26
- 主要终点
- Evaluate subjects treated with ALX1-11 (no calcium supplementation) increase in BMD is less than those treated with ALX1-11 (receiving calcium supplementation).
研究概览
简要总结
This study is evaluating the effects of calcium supplementation on the efficacy and safety of recombinant parathyroid hormone (ALX1-11) in postmenopausal women with osteoporosis. The primary objective of this clinical study is to evaluate whether increases in bone mineral density (BMD) for subjects treated with ALX1-11 and receiving no calcium supplementation are less than increases in BMD observed for subjects treated with ALX1-11 and receiving calcium supplementation.
详细描述
Effects of ALX1-11 on bone mineral density (BMD) have been documented in a dose-finding Phase II clinical trial in osteoporotic postmenopausal women, supplemented with calcium and Vitamin D3 but without any other treatment for osteoporosis. The anabolic effects of ALX1-11 in the lumbar vertebrae were statistically significant after the 12-month treatment period and more pronounced than any approved therapy. Additionally, animal studies have shown that the new bone formed by treatment with ALX1 11 is of good quality both histologically and biomechanically.
The primary objective of this clinical study is to evaluate whether increases in bone mineral density (BMD) for subjects treated with ALX1-11 and receiving no calcium supplementation are less than increases in BMD observed for subjects treated with ALX1-11 and receiving calcium supplementation.
A secondary objective of this clinical study are to evaluate whether changes in other efficacy parameters, such as bone mineral content (BMC) and biochemical markers of bone turnover, for subjects treated with ALX1-11 and receiving no calcium supplementation are less than increases observed for subjects treated with ALX1-11 and receiving calcium supplementation.
This is a double-blind, multi-centered, randomized, placebo-controlled, parallel-group study comprised of 3 treatment groups: ALX1-11 injection plus oral calcium, ALX1-11 injection plus oral placebo calcium, and placebo ALX1-11 injection plus oral calcium. All subjects also receive 400 IU oral vitamin D3. The dose of ALX1-11 to be used in this study is 100 μg, self administered by daily sc injection. The calcium dose is 700 mg/day.
Additional supplemental calcium and/or Vitamin D3 will not be permitted. Patients will be monitored for the development of hypercalcemia and/or hypercalciuria.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 45 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Women who are capable of understanding and giving written, voluntary informed consent before the clinical study screening visit
- •Women with the ability to self-administer a daily injection or having a designee who will give the injections
- •Women who are postmenopausal with at least one year since their last menstruation. If a subject's menopausal status at screening is in question, because of history or because the subject had a hysterectomy without oophorectomy, a follicle-stimulating hormone (FSH) level >40 mIU/mL will satisfy the definition of postmenopausal status.
- •Women 45-54 years of age with the following T-score and/or vertebral fracture
- •T-score >=3.0 standard deviations (SD) below mean peak bone mass of young women at the lumbar spine, femoral neck, or total hip Or
- •T-score >=2.5 SD below mean peak bone mass of young women at the lumbar spine, femoral neck, or total hip with a prevalent vertebral fracture verified by the central imaging organization before the subject is enrolled into the study
- •Women >=55 years of age with the following T-score and/or vertebral fracture:
- •o T-score >=2.5 SD below mean peak bone mass of young women at the lumbar spine, femoral neck, or total hip Or
- •T-score >=2.0 SD below mean peak bone mass of young women at the lumbar spine, femoral neck, or total hip with a vertebral fracture verified by the central imaging organization before the subject is enrolled into the study
- •The following types of vertebral fractures should not be considered for subject enrollment into this study:
- •Pathological fractures due to malignant disease or infection
- •Fractures due to excessive trauma sufficient to cause a fracture in young individuals with normal bone mass
排除标准
- •A. Vertebral Deformity (assessed as described in Appendix 2 of the protocol, are sufficient for exclusion):
- •· Vertebral deformities
- •Patient has 5 or more vertebral (thoracic and lumbar) fractures
- •Patient has 2 or more lumbar vertebral deformities (L1 to L4)
- •B. DXA Imaging:
- •· Inability to have a DXA scan performed, e.g.:
- •A history of a lumbar laminectomy which interferes with the DXA measurement of the lumbar vertebrae
- •The presence of pedicle screws
- •The patient cannot lay flat on her back for the required time to provide accurate imaging
- •Patient is not able to have an A/P lumbar vertebral DXA performed
- •Patient has a history of vertebroplasty
- •Any other excessive degenerative disease which interferes with the DXA measurement of the lumbar vertebrae or hip
- •C. History of or Concurrent Illness:
- •Disorders of Immunity
- •Significant* immunological disorders
- •Endocrine system
- •Any history of hyper- or hypoparathyroidism
- •Cushing's disease
- •Hyperthyroidism (within 12 months)
- •Significant* endocrine disorders
- •Gastrointestinal system
- •Significant* gastrointestinal disorders
- •Kidney and collecting system
- •Clinically significant* history of nephrolithiasis or urolithiasis
- •Current impaired renal function and/or verified kidney calcification*
- •Significant* renal disorders
- •Liver, biliary tract and pancreatic systems
- •Active hepatitis or pancreatitis
- •Significant* hepatic or pancreatic disorders
- •Musculoskeletal system
- •Any history of other metabolic bone diseases within the past 5 years, (e.g., Paget´s disease, osteogenesis imperfecta, osteomalacia)
- •Subjects with chronic, active joint disease and/or joint infection
- •Neoplasia - Any history of bone cancer or any cancer within the previous 5 years, with the exception of squamous or basal cell carcinoma**
- •(**)Patients who have had either squamous or basal cell carcinoma of the skin can enroll if:
- •The lesion(s) were fully resected with clear margins described in a written report by a pathologist, and
- •The patient has had no recurrence of lesions for at least one year from the time of the original resection.
- •· Nervous system
- •Significant* neurological or psychiatric disease
- •· Vascular, respiratory and cardiac system
- •Significant* unstable cardiac or pulmonary disease
- •(*) Significance will be determined by the investigator on the basis of history, physical exam, and/or laboratory screens. Significant disorders necessitate ongoing changes in therapeutic medication or frequent monitoring.
- •D. Concurrent Medication:
- •Patients cannot be enrolled into this clinical trial if they have received any of the following therapies at any time:
- •Any PTH or PTH analogs [e.g., rhPTH(1-84), PTH(1-34), PTHrP and analogs]
- •Strontium
- •Patients must have been off the following agents for the specified times before entering the screening phase of this clinical trial:
- •Any investigational drug (>30 days)
- •Anabolic steroids or androgens (>6 consecutive months)
- •Active Vitamin D3 metabolites and analogs, e.g., calcitriol (>90 days)
- •Provera (medroxyprogesterone) (According to label instructions)
- 另有 49 项未显示
研究组 & 干预措施
1
PTH 100 mcg and 700 mg calcium
干预措施: PTH/Calcium (Drug)
2
PTH 100 mcg and placebo
干预措施: PTH/placebo (Drug)
3
Placebo and 700 mg calcium
干预措施: placebo (Drug)
结局指标
主要结局
Evaluate subjects treated with ALX1-11 (no calcium supplementation) increase in BMD is less than those treated with ALX1-11 (receiving calcium supplementation).
时间窗: 6 months
Primary efficacy variable is the percentage change from baseline of lumbar vertebral BMDmeasured by DXA.
时间窗: 6 months
次要结局
- BMC,(6 months)
- biochemical markers of bone turnover for subjects treated with ALX1-11 and receiving no calcium versus those receiving ALX1-11 with calcium supplementation.(6 months)
- Percentage change from baseline in biochemical markers of bone turnover: 1) Bone formation: Serum BSAP and P1NP 2) Bone resorption: Serum CTx, urinary NTx(6 months)
- Incidence of hip fractures(6 months)
- Percentage change from baseline of trabecular volumetric BMD of spine as assessed by QCT (sub-study)(6 months)
- vBMD,(6 months)
- height,(6 months)
- Percentage change from baseline of lumbar vertebral BMC(6 months)
- Percentage change from baseline of trabecular volumetric BMD of hip as assessed by QCT (sub-study)(6 months)
- the incidence of clinical fractures,(6 months)
- 12 lead ECG changes(6 months)
- Adverse Events(6 months)
- Incidence of new and/or worsened vertebral (thoracic and lumbar) fractures(6 months)
- Percentage change from baseline of total hip BMD and BMC(6 months)
- Incidence of any clinical fractures (vertebral and/or non-vertebral)(6 months)
- Incidence of clinical fractures other than hip, or thoracic or lumbar vertebrae(6 months)