A Double Blind, Placebo Controlled, Parallel-Group Study to Assess the Safety and Efficacy of 3 Doses of ALX1-11 (50, 75, and 100µg) in the Treatment of Postmenopausal Osteoporosis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Shire
- 入组人数
- 217
- 试验地点
- 19
- 主要终点
- Efficacy was assessed as percent change from baseline in BMD, BMC, and BMA at the lumbar spine, total hip, femoral neck and whole body (excluding the head) using DXA.
研究概览
简要总结
A double-blind, placebo-controlled, parallel-group study to assess the safety and efficacy of 3 doses of ALX1-11 (recombinant human parathyroid hormone [rhPTH(1-84)])(50, 75 and 100 µg) in the treatment of postmenopausal osteoporosis. The primary objective of this study is to compare the efficacy of ALX1-11 (50, 75 and 100 µg) with that of placebo in terms of increasing vertebral bone mineral density, when given daily by subcutaneous injection for 12 months in postmenopausal women with osteoporosis.
详细描述
Human clinical experience with a synthetic human parathyroid hormone fragment (rhPTH 1-34) and animal studies with ALX1-11 demonstrate consistent increases in bone mineral density. Furthermore, the newly formed bone is normal in structure and composition. Therefore, ALX1-11 (recombinant human parathyroid hormone [rhPTH 1-84]) has the potential to stimulate new bone formation in osteoporotic patients thereby increasing trabecular bone density and preventing fractures. The clinical profile for ALX1-11 can be expected to be unique, since none of the approved therapies for osteoporosis are able to form the quantities of new bone that ALX1-11 is potentially capable of. Patients with bone density below the "fracture threshold" (osteopenia), as well as those with established vertebral fractures (osteoporosis), would be expected to benefit from treatment.
Animal toxicology studies have been completed and there were no results to indicate any restrictions in the clinical usage of the drug. Preliminary human clinical experience with ALX1-11 in healthy, postmenopausal females has demonstrated no apparent risk of frank hypercalcemia* at single administrations up to 5.0 µg/kg or daily administrations for 7 days up to 2.0 µg/kg/day.
Based on these studies, the anticipated therapeutic range of ALX1-11 is 50-100 µg per day (approx. 1.0 - 1.5 µg/kg/day). Therefore, the dose range to be tested in this study will include an anticipated minimally effective dose, interim dose and maximally tolerable dose (50, 75 and 100 µg). The efficacy of 3 doses of ALX1-11 will be assessed in terms of bone mineral density and biochemical markers of bone turnover in postmenopausal women.
The primary objective of this study is to determine the dose-response relationship of ALX1-11 in terms of bone mineral density. The efficacy of the 3 doses of ALX1-11 relative to placebo will be determined by measurement of bone mineral density (by DXA) at baseline and at 3, 6 and 12 months.
Patients will administer a daily subcutaneous injection of 0.5 mL of either 50, 75 or 100 µg of ALX1-11 or placebo every morning for 12 months.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 50 Years 至 75 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Post-menopausal women aged 50-75 years at Visit 1 (at least 5 years post cessation of menses, or FSH>20 IU/L, serum estradiol <110 pmol/L)
- •Vertebral bone mineral density at least 2.5 S.D. below the mean of young normals. Patients must have at least 2 measurable contiguous vertebral bodies in the lumbar region, L1-L
- •Ability to self administer injections
- •Ability and willingness to give informed consent
排除标准
- •Evidence of 5 or more vertebral fractures
- •Evidence of 2 or more vertebral fractures in the region L1-L4
- •Presence of significant cardiac disease as determined by history, physical examination and laboratory screens e.g. cardiac dysrhythmias.
- •Presence of significant hepatic, renal, pulmonary, gastrointestinal, hematological, endocrine, immunologic, neurological or psychiatric disease as determined by history, physical examination and laboratory screens. Specifically excluded are diseases known to contribute to osteoporosis: hyperparathyroidism, hyperthyroidism, glucocorticoid excess, hyper or hypocalcemia, Paget's disease, osteogenesis imperfecta, osteomalacia and severe scoliosis.
- •Evidence of lumbar fusions, osteophytes or excessive degenerative disease which precludes reasonable DXA measurement.
- •History or presence of cancer within the previous 5 years except for superficial basal cell and squamous cell carcinomas of the skin.
- •Treatment with any of the following therapies:
- •Any form of Estrogen within previous 6 months
- •Prior use of Etidronate for more that 2 treatment cycles (2weeks/cycle) and/or any use within prior 6 months
- •Any other bisphosphonate
- •Parathyroid Hormone use within 6 months
- •Fluoride (>10 mg/day) within 12 months
- •Any form of Calcitonin within previous 4 months
- •Thyroid hormone within previous 4 months unless TSH levels found to remain within normal range
- •Other therapies known to influence bone metabolism* within previous 4 months
- •Any investigational compound within previous 3 months
- •Abnormal serum Ca++ level: patients having two (2) consecutive serum calcium above 2.66 mmol/L (10.6 mg/dl) will be excluded.
- •History of positive test for Hepatitis B or C, or urine drug screen.
- •History of alcohol or drug abuse: an excess of alcohol is defined as more than 4 or any combination of more than four (4) of the following per day: 120 mL wine, 360 mL beer or wine cooler or 30 mL whiskey.
- •Weight more than 25% above ideal body weight, (minimum 45 kg) as listed in the Metropolitan Life Insurance Tables (Appendix 3)
- •Deemed unsuitable, in the opinion of the investigator, for any other reason.
- •(*Chronic or continued use of medication that may affect bone calcium metabolism, e.g. thiazide diuretics, oral or injectable steroids, antimitotics (methotrexate), heparin, anticonvulsants and supplements of Vitamin D in excess of 1,000 IU per day and Vitamin A in excess of 10,000 IU per day)
研究组 & 干预措施
1
Placebo drug injectable subcutaneously
干预措施: placebo (Drug)
2
50 mcg PTH(1-84)
干预措施: ALX1-11 50 mcg (Drug)
3
75mcg PTH(1-84)
干预措施: ALX1-11 75mcg (Drug)
4
100 mcg PTH(1-84)
干预措施: ALX1-11 (Drug)
结局指标
主要结局
Efficacy was assessed as percent change from baseline in BMD, BMC, and BMA at the lumbar spine, total hip, femoral neck and whole body (excluding the head) using DXA.
时间窗: 12 months of treatment
次要结局
- Secondary efficacy evaluations were also performed at Month 3, 6, and 12: Percent change from baseline in lumbar spine BMC and BMA; Percent change from baseline in total hip and femoral neck BMD, BMC and BMA(12 months)