A 52 Week Randomized, Double-Blind, Multicenter, Mechanistic Study With a 24 Week Open-Label Follow-Up to Evaluate the Effect of AVANDIA TM on Bone in Postmenopausal Women With Type 2 Diabetes Mellitus
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 226
- 试验地点
- 1
- 主要终点
- Adjusted Percent Change From Baseline in Femoral Neck (FN) Bone Mineral Density (BMD) Via Dual-energy X-ray Absorptiometry (DXA) at Week 52
研究概览
简要总结
The purpose of this study is to determine the effects of rosiglitazone on the bone in postmenopausal women with type 2 diabetes mellitus
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
- 55 Years 至 80 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Female, >55 to <80 years
- •>5 years menopausal
- •Type 2 Diabetes Mellitus (T2DM) diagnosis according to American Diabetes Association (ADA), American Association of Clinical Endocrinologists (AACE), Canadian Diabetes Association (CDA), World Health Organization/International Diabetes Federation (WHO/IDF)
- •Drug-naïve (HbA1c < or = 9.0%); OR Prior monotherapy, submaximal doses of metformin (< or = 1000mg Metformin), sulfonylureas (< or = 5mg Glyburide, < or = 10mg Glipizide or < or = 8mg glimepiride) or full dose Januvia (100mg) (HbA1c < or = 8.5%); OR Prior monotherapy, > submaximal doses of metformin (>1000mg) or sulfonylureas (>5mg Glyburide, >10mg Glipizide or >8mg glimepiride) (HbA1c < or = 7.0%)
- •Weighs <300 lbs (136.4 kg)
- •Two or more vertebra (L1-L4) suitable for BMD measurement by dual x-ray absorptiometry (DXA)
- •Absolute BMD value consistent with T-score >-2.5 at femoral neck, lumbar spine and total hip
排除标准
- •Type 1 Diabetes Mellitus (T1DM) or history of diabetic ketoacidosis (DKA)
- •Renal or hepatic disease (clinically significant)
- •Hepatocellular reaction, severe edema, or medically serious fluid event associated with thiazolidinedione (TZD)
- •Recent (<6mos) history or clinical intervention for angina or myocardial infarction or is taking nitrates
- •Any stage of heart failure, i.e. New York Heart Association (NYHA) class I-IV
- •Systolic BP >160mmHg or diastolic BP >90mmHg while on antihypertensive
- •Hypersensitivity to TZDs, biguanides
- •Prior treatment with two or more oral anti-diabetic (OAD) agents
- •Bilateral hip replacements
- •Concurrent diseases affecting bone metabolism
- •Active malabsorption syndrome
- •Serum calcium outside the central lab reference range
- •Thyroid replacement therapy, serum thyroid stimulating hormone (TSH) must be within range
- •Vitamin D deficiency
- •Previous treatment with: strontium, intravenous (IV) bisphosphonate, fluoride, hormones, calcineurin inhibitors or methotrexate
- •Chronic systemic corticosteroid [e.g. glucocorticoid, mineralocorticoid] treatment of no more than two intra-articular injections within the past year or use of oral parenteral, or long-term, high-dose inhaled corticosteroids
研究组 & 干预措施
Arm 2 Treatment B
metformin up to 2000mg/day
干预措施: Metformin (Drug)
Arm 1 Treatment A
rosiglitazone up to 8mg/day
干预措施: Rosiglitazone (Drug)
结局指标
主要结局
Adjusted Percent Change From Baseline in Femoral Neck (FN) Bone Mineral Density (BMD) Via Dual-energy X-ray Absorptiometry (DXA) at Week 52
时间窗: Baseline and Week 52
FN BMD (measured in grams per centimeters squared \[g/cm\^2\]) was measured by DXA. Bone mineral density is calculated as the mineral content of a bone divided by the area of the bone. DXA is the principal technique used for measuring BMD. Percent change from Baseline at Week 52 was calculated as (BMD at Week 52 minus BMD at Baseline)/BMD at Baseline x 100% and was assessed by analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region. Change in FN BMD at Week 52 was only analyzed within the Rosiglitazone arm.
Adjusted Percent Change in Femoral Neck (FN) Bone Mineral Density (BMD) Via Dual-energy X-ray Absorptiometry (DXA) From Week 52 +10 Days to Week 76+10 Days
时间窗: Week 52+10 days and Week 76+10 days
FN BMD (measured in grams per centimeters squared \[g/cm\^2\]) was measured by DXA. Bone mineral density is calculated as the mineral content of a bone divided by the area of the bone. DXA is the principal technique used for measuring BMD. Percent change from Week 52+10 days to Week 76+10 days was calculated as (BMD at Week 76+10 days minus BMD at Week 52+10 days)/BMD at Week 52+10 days x 100% and was assessed by analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region.
Adjusted Percent Change From Baseline in Femoral Neck (FN) Bone Mineral Density (BMD) Via Dual-energy X-ray Absorptiometry (DXA) at Week 76+10 Days
时间窗: Baseline and Week 76+10 days
FN BMD (measured in grams per centimeters squared \[g/cm\^2\]) was measured by DXA. Bone mineral density is calculated as the mineral content of a bone divided by the area of the bone. DXA is the principal technique used for measuring BMD. Percent change from Baseline at Week 76+10 days was calculated as (BMD at Week 76+10 days minus BMD at Baseline)/BMD at Baseline x 100% and was assessed by analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region.
次要结局
- Adjusted Percent Change From Baseline in Bone Specific Alkaline Phosphatase (BSAP) and Procollagen Type 1 N-propeptide (P1NP) at Week 52 and Week 76(Baseline, Week 52, and Week 76)
- Adjusted Percent Change in Carboxyterminal Cross-linked Telopeptide of Type 1 Collagen (CTX) From Week 52 to Week 76(Week 52 and Week 76)
- Adjusted Percent Change in 25-Hydroxyvitamin D (Vitamin D) From Week 52 to Week 76(Week 52 and Week 76)
- Adjusted Percent Change From Baseline in Intact Parathyroid Hormone (PTH) at Week 52 and Week 76(Baseline, Week 52, and Week 76)
- Adjusted Percent Change in Intact Parathyroid Hormone (PTH) From Week 52 to Week 76(Week 52 and Week 76)
- Percent Change From Baseline in Serum Estradiol at Week 52 and Week 76(Baseline, Week 52, and Week 76)
- Percent Change From Baseline in Total Testosterone at Week 52 and Week 76(Baseline, Week 52, and Week 76)
- Adjusted Percent Change From Baseline in Femoral Neck, Total Hip, Trochanter, and Lumbar Spine BMD Via DXA at Week 52(Baseline and Week 52)
- Adjusted Percent Change in Femoral Neck, Total Hip, Trochanter, and Lumbar Spine BMD Via DXA From Week 52+30 Days to Week 76 + 30 Days(Week 52 + 30 days and Week 76 + 30 days)
- Adjusted Percent Change in Bone Specific Alkaline Phosphatase (BSAP) and Procollagen Type 1 N-propeptide (P1NP) From Week 52 to Week 76(Week 52 and Week 76)
- Percent Change in Serum Estradiol From Week 52 to Week 76(Week 52 and Week 76)
- Adjusted Percent Change in Femoral Neck, Total Hip, Trochanter, and Lumbar Spine BMD Via DXA From Week 52+10 Days to Week 76 + 10 Days(Week 52 + 10 days and Week 76 + 10 days)
- Adjusted Percent Change From Baseline in Carboxyterminal Cross-linked Telopeptide of Type 1 Collagen (CTX) at Week 52 and Week 76(Baseline, Week 52, and Week 76)
- Percent Change in Total Testosterone From Week 52 to Week 76(Week 52 and Week 76)
- Adjusted Percent Change From Baseline in 25-Hydroxyvitamin D (Vitamin D) at Week 52 and Week 76(Baseline, Week 52, and Week 76)
- Percent Change From Baseline in Free Testosterone at Week 52 and Week 76(Baseline, Week 52, and Week 76)
- Percent Change in Sex Hormone Binding Globulin (SHBG) From Week 52 to Week 76(Week 52 and Week 76)
- Percent Change in Free Testosterone From Week 52 to Week 76(Week 52 and Week 76)
- Percent Change From Baseline in Sex Hormone Binding Globulin (SHBG) at Week 52 and Week 76(Baseline, Week 52, and Week 76)