A Randomized, Multicenter, Double-Blind, Parallel-Group, Placebo-Controlled Study to Investigate the Efficacy and Safety of Canagliflozin in Children and Adolescents (≥10 to <18 Years) With Type 2 Diabetes Mellitus
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 171
- 试验地点
- 106
- 主要终点
- Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 26
研究概览
简要总结
The purpose of this study is to assess the effect of canagliflozin relative to placebo on glycated hemoglobin (HbA1c) after 26 weeks of treatment, and to assess the overall safety and tolerability of canagliflozin.
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
- 10 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants with a diagnosis of type 2 diabetes mellitus (T2DM)
- •Random C-peptide at screening greater than (>)0.6 nanogram/milliliter (ng/mL) (>0.2 nanomole/liter [nmol]/L])
- •HbA1c of greater than or equal to (>=)6.5 percent (%) to less than or equal to (<=)11.0% and meets 1 of the inclusion criteria below:
- •On diet and exercise only for at least 4 weeks prior to screening
- •On diet and exercise and a stable dose of metformin monotherapy >=1,000 mg per day or MTD per day for at least 8 weeks prior to screening
- •On diet and exercise and a stable insulin monotherapy regimen for at least 8 weeks prior to screening (stable dose is defined as no change in the insulin regimen [that is, type{s} of insulin] and <=15% change in the total daily dose of insulin [averaged over 1 week to account for day to day variability])
- •On diet and exercise and a stable combination therapy with metformin and insulin for at least 8 weeks prior to screening
排除标准
- •History of diabetic ketoacidosis (DKA), type 1 diabetes mellitus (T1DM), pancreas or cell transplantation, or diabetes secondary to pancreatitis or pancreatectomy or maturity onset diabetes of the young (MODY)
- •Participants on any antihyperglycemic agents (AHAs) other than metformin, or injectable insulin within 8 weeks of the first dose of study drug (that is Day 1)
- •Repeated (2 or more over a 1-week period) fasting self-monitoring of blood glucose (SMBG) measurements >270 milligram/deciliter (mg/dL) (>15 millimole/liter [mmol/L]) during the pretreatment phase, despite reinforcement of diet and exercise counseling
- •Severe hypoglycemia within 6 months prior to Day 1
- •History of hereditary glucose-galactose malabsorption or primary renal glucosuria
- •Alanine aminotransferase level >5.0 times the upper limit of normal (ULN) or total bilirubin >1.5 times the ULN at screening (for elevations in bilirubin: if, in the opinion of the investigator and agreed upon by the sponsor's medical officer, the elevation in bilirubin is consistent with Gilbert's disease, the subject may participate)
研究组 & 干预措施
Single-blind run-in Period: Placebo
Participants will receive 1 placebo tablet matching canagliflozin 100 milligram (mg) once-daily during the 2-week single-blind placebo run-in period.
干预措施: Placebo (Drug)
Double-blind Treatment Phase: Canagliflozin or Placebo
Canagliflozin 100 mg/matching placebo once-daily during first 12 weeks. At Week 13, participants who have glycated hemoglobin (HbA1c) of greater than or equal to (>=)7.0 percent (%), estimated glomerular filtration rate (eGFR) >=60 milliliter/minute/1.73 meter square (mL/min/1.73 m^2) will be re-randomized to either remain on canagliflozin 100 mg/matching placebo or up-titrate to canagliflozin 300 mg/matching placebo till Week 52.
干预措施: Canagliflozin 100 mg (Drug)
Double-blind Treatment Phase: Canagliflozin or Placebo
Canagliflozin 100 mg/matching placebo once-daily during first 12 weeks. At Week 13, participants who have glycated hemoglobin (HbA1c) of greater than or equal to (>=)7.0 percent (%), estimated glomerular filtration rate (eGFR) >=60 milliliter/minute/1.73 meter square (mL/min/1.73 m^2) will be re-randomized to either remain on canagliflozin 100 mg/matching placebo or up-titrate to canagliflozin 300 mg/matching placebo till Week 52.
干预措施: Canagliflozin 300 mg (Drug)
Double-blind Treatment Phase: Canagliflozin or Placebo
Canagliflozin 100 mg/matching placebo once-daily during first 12 weeks. At Week 13, participants who have glycated hemoglobin (HbA1c) of greater than or equal to (>=)7.0 percent (%), estimated glomerular filtration rate (eGFR) >=60 milliliter/minute/1.73 meter square (mL/min/1.73 m^2) will be re-randomized to either remain on canagliflozin 100 mg/matching placebo or up-titrate to canagliflozin 300 mg/matching placebo till Week 52.
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 26
时间窗: Baseline (Day 1) and Week 26
Change from baseline in HbA1c at Week 26 was analyzed using a pattern mixture model with multiple imputation. Data for this outcome measure was planned to be collected and analyzed for the combined population of arm Canagliflozin 100 mg and Canagliflozin 300 mg.
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)
时间窗: Baseline (Day 1) up to 30 days post last dose at Week 52 (up to Week 56)
An AE was any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non investigational) product. An AE did not necessarily have a causal relationship with the pharmaceutical/biological agent under study. TEAE was defined as the AEs occurring after first administration of double blind study intervention up to 30 days post last dose of study intervention.
次要结局
- Change From Baseline in Fasting Plasma Glucose (FPG) at Weeks 26 and 52(Baseline (Day 1), Weeks 26 and 52)
- Percentage of Participants With HbA1c Less Than (<)7.5 Percent (%), <7%, and <6.5% at Weeks 26 and 52(Weeks 26 and 52)
- Percentage of Participants Who Received Rescue Therapy(Baseline (Day 1) up to Week 52)
- Time to Rescue Therapy(Baseline (Day 1) up to Week 52)
- Percent Change From Baseline in Body Weight at Weeks 26 and 52(Baseline (Day 1), Weeks 26 and 52)
- Change From Baseline in Body Mass Index (BMI) at Weeks 26 and 52(Baseline (Day 1), Weeks 26, and 52)
- Percent Change From Baseline in Fasting Plasma Lipids Levels at Weeks 26 and 52(Baseline (Day 1), Weeks 26, and 52)
- Percent Change From Baseline in LDL-C to HDL-C Ratio and Non-HDL-C to LDL-C Ratio at Weeks 26 and 52(Baseline (Day 1), Weeks 26, and 52)
- Change From Baseline in Systolic Blood Pressure at Weeks 26 and 52(Baseline (Day 1), Weeks 26 and 52)
- Change From Baseline in Diastolic Blood Pressure at Weeks 26 and 52(Baseline (Day 1), Weeks 26, and 52)
- Change From Baseline in HbA1c at Weeks 12 and 52(Baseline (Day 1), Weeks 12, and 52)
- Growth Velocity at Weeks 26 and 52(Baseline (Day 1) and Weeks 26 and 52)
- Number of Participants With Changes in Tanner Staging (Females) From Baseline at Weeks 26 and 52(Baseline (Day 1), Weeks 26, and 52)
- Number of Participants With Changes in Tanner Staging (Males) From Baseline at Weeks 26 and 52(Baseline (Day 1), Weeks 26, and 52)
- Change From Baseline in Bone Turnover Marker: Serum Osteocalcin and Serum Collagen Type 1 Carboxy-Telopeptide (CTx) at Weeks 26 and 52(Baseline (Day 1), Weeks 26 and 52)
- Urinary Albumin/Creatinine Ratio (ACR) at Weeks 26 and 52(Weeks 26 and 52)