A Randomized, Double-Blind, Multiple Dose, Placebo-Controlled, Parallel Group, 48-Week, Study of Oral Recombinant Salmon Calcitonin (rsCT) Compared to Salmon Calcitonin (sCT) Nasal Spray in Postmenopausal Osteoporotic Women
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 565
- 试验地点
- 20
- 主要终点
- Percent Change From Baseline in Bone Mineral Density (BMD) of Axial Lumbar Spine
研究概览
简要总结
The purpose of this study is to compare the effectiveness and tolerability of two medications, calcitonin nasal spray and a tablet containing calcitonin, in postmenopausal women with osteoporosis. Osteoporosis is the term used to describe a large group of diseases, which are characterized by loss of bone density, which makes the bones weaker. Osteoporosis often occurs in postmenopausal women.
Calcitonin is a hormone found in the human body. Together with other substances, it regulates the concentration of calcium in the blood and inhibits the natural resorption of bone. Both medications in this study contain salmon calcitonin (sCT), because this form of calcitonin is more active than human calcitonin when used as a medicine.
The calcitonin Nasal Spray used in this study is registered and available to doctors in United States for the treatment of osteoporosis. The medication being tested in this study is an oral tablet form of salmon calcitonin.
详细描述
This was a randomized, double-blind, double-dummy, multiple dose, placebo-controlled, parallel group, 48- week, Phase III study. Women age 45 and over who were postmenopausal and had a diagnosis of osteoporosis were eligible for the study and were randomly allocated to one of three treatment groups; placebo tablets, oral rsCT tablets or calcitonin nasal spray. Each patient was given a treatment kit, which contained the study medication to which she had been assigned and a placebo of the treatment to which she was not assigned, or placebo nasal and oral preparations, as well as the required dietary supplements (calcium and vitamin D tablets). The study medication and supplements were self-administered at home. It was anticipated that approximately 545 patients would participate in the study.
EFFICACY: Bone Mineral Density (BMD) was recorded at Screening, Week 24, and Week 48. CTx-1 and N-telopeptide of collagen 1 (NTx-1), biochemical markers of bone resorption and total Procollagen type 1 N-terminal propeptide (P1NP),a marker of bone formation, were assessed at Week 0, Week 24, and Week 48. SAFETY: Adverse events were assessed at the clinic at Weeks 0, 12, 24, 36 and 48, and by interim phone calls at Weeks 4, 8, 16, 20, 28, 32, 40, 44, and 52. At Screening, Week 12, and Week 48, a physical examination, including nasal exam, was performed and specimens for safety laboratory analysis (clinical chemistry, hematology, and urinalysis) were collected. Sera for immunogenicity evaluations were collected at Baseline, Week 12, and Week 48.
EFFICACY: The primary comparison of interest was the percent change from baseline to 48 weeks in axial lumbar spine (L1 to L4) corrected BMD comparing the rsCT oral tablet group and the calcitonin nasal spray group. The model included the factors of the covariate (baseline BMD), treatment group, and center. The hypothesis to be tested was performed to examine the non-inferiority of the oral tablet group to the nasal spray group with respect to the percent change in axial lumbar L1-L4 spine corrected BMD. Specifically, the null hypothesis to be tested was: [Mean(oral) - Mean(placebo)] - 0.5 x [Mean(nasal) - Mean(placebo)] < 0 The alternative hypothesis was that the above expression was > 0, which implied that the oral tablet group was non-inferior to nasal spray group. The primary analysis of interest employed the modified intent-to-treat population.
SAFETY: Adverse events were summarized descriptively. Mean vital signs and clinical laboratory test results in each treatment group were compared using a one-way analysis of variance. Additionally, shift tables were prepared for each laboratory variable.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Female and age 45 or over.
- •Must have undergone the onset of spontaneous or surgical menopause. Spontaneous menopause is defined as 12 months of spontaneous amenorrhea or 6 months of spontaneous amenorrhea with serum Follicle Stimulating Hormone (FSH) levels >40 milli-international units (mIU)/milliliter (mL) or 6 weeks post-surgical bilateral oophorectomy with or without hysterectomy.
- •Diagnosis of osteoporosis on the basis of an axial lumbar spine, femoral neck or total hip BMD which is below the mean for premenopausal women by a magnitude of at least 2.5 SD or 2.0 SD, if there is a documented history of a vertebral fragility fracture.
- •Must have at least three contiguous lumbar vertebrae (L1-L4) that are evaluable by DXA for BMD that is, without fracture or significant degenerative disease, as determined by Bio-Imaging Technologies, Inc.
- •No clinically significant abnormal findings in the medical history, physical exam or nasal exam.
- •No clinically significant abnormal laboratory values at the screening assessment.
排除标准
- •History of severe allergic disease.
- •History of metabolic and other bone diseases, including osteogenesis imperfecta, osteomalacia, and Paget's disease.
- •Vitamin D insufficiency defined as a 25 hydroxyvitamin D level <20 ng/mL.
- •Use of any intravenous bisphosphonate in the past 24 months, or >2 doses of intravenous bisphosphonate ever.
- •Use of oral bisphosphonate before randomization, including investigational bisphosphonates, unless: 1) less than 6 months of treatment and off for 6 months, or 2) 6 to 12 months of treatment and off for 2 years, or 3) More than 12 months of treatment and off for 5 years
- •Use of denosumab, fluoride, or strontium, ever.
- •Use of parathyroid hormone analogs or other bone metabolic agents within 1 year preceding randomization.
- •Any condition or disease that may interfere with the ability to have a DXA scan or to evaluate a DXA scan, for example, severe osteoarthritis of the spine, spinal fusion, pedicle screws, history of vertebroplasty, or degenerative disease that results in insufficient number of evaluable lumbar vertebrae, or more than 1 lumbar vertebral fracture in L1 through L
- •(More than 4 vertebral fractures in T4 through L4; Bilateral hip replacements)
- •Use of anabolic steroids or androgens within 6 months preceding randomization.
- •Use of Vitamin D metabolites and analogs, (e.g., calcitriol) within 3 months preceding randomization). Note: Vitamin D supplementation is not exclusionary.
- •Use of estrogen or estrogen-related drugs, for example, tamoxifen, tibolone, or raloxifene within 3 months preceding randomization.
- •Use of coumadin within 4 weeks preceding randomization or heparin within 1 week preceding randomization.
- •Chronic systemic treatment with glucocorticoids, hormone replacement therapy, calcitonin or any other medication within the previous three months which, in the opinion of the Investigator, would interfere with the study.
- •Clinically relevant abnormal history, physical findings or laboratory values at the pre-study screening assessment that could interfere with the objectives of the study or the safety of the patient.
- •Presence of acute or chronic illness or history of chronic illness which, in the judgment of the Investigator, makes participation in the study medically inappropriate.
- •Uncontrolled hypertension, significant gastrointestinal abnormalities, uncontrolled diabetes mellitus, significant coronary heart disease, any psychotic mental illness, chronic allergic rhinitis, asthma, uncorrected endocrine dysfunction, or significantly impaired hepatic, respiratory or renal function.
- •History of drug or alcohol abuse, or intake of more than 30 units of alcohol weekly.
研究组 & 干预措施
Oral calcitonin and placebo nasal spray
Intervention: Oral calcitonin tablet (along with placebo intranasal spray)
干预措施: Oral Calcitonin Tablets (Drug)
Intranasal calcitonin & oral placebo
Intervention: Commercially available, active comparator, intranasal calcitonin-salmon (plus matching oral placebo tablet).
干预措施: Intranasal Calcitonin (Drug)
Placebo: tablet & intranasal spray
Intervention: Both oral matching placebo tablets and matching intranasal placebo spray
干预措施: Placebo tablets and placebo intranasal spray (Drug)
结局指标
主要结局
Percent Change From Baseline in Bone Mineral Density (BMD) of Axial Lumbar Spine
时间窗: 48 weeks
Bone Mineral Density is measured by Dual-Energy X-ray Absorptiometry (DXA) body scans. Two scans were taken for each timepoint(baseline, week 24 and week 48) and the mean of the two values was entered. The primary outcome timepoint was 48 weeks, but if a patient did not complete the full study, then the 24 week BMD value was used as Last Observation Carried Forward. The percentage change from the baseline value, set as 0%, was recorded as the primary outcome measure.
次要结局
- Change in Plasma C-terminal Telopeptide of Collagen 1 (CTx-1)(24 weeks)
- Change in Plasma CTx-1 From Baseline(48 weeks)