A Multi Center, Randomized, Double Blind, Placebo-controlled, Dose Escalation Study of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ACZ885 Administered Intravenously to Patients With Type 2 Diabetes Mellitus
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Novartis
- 入组人数
- 231
- 试验地点
- 8
- 主要终点
- Mean Change From Baseline in Plasma HbA1c (Glycosylated Hemoglobin / Hemoglobin A1c)
研究概览
简要总结
The purpose of this study was to evaluate, in patients with Type 2 Diabetes Mellitus, whether Canakinumab can lower Glycosylated hemoglobin / hemoglobin A1c (HbA1c) and/or peak glucose levels in response to an oral glucose tolerance test (OGTT).
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
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female patients aged 18 to 70 years, with type 2 diabetes mellitus (non-insulin dependent diabetes) for at least 6 months prior to study start
- •HbA1c between 7.0 and 9.5%
- •On stable dose metformin monotherapy
- •Stable body weight
排除标准
- •Poorly controlled type 2 diabetes (very low or very high blood sugar levels, or other indicators of poor control)
- •Acute infections prior to dosing
- •Patients with type 1 diabetes (insulin-dependent diabetes)
- •Taking diabetes medication (other than metformin)
- •Other protocol-defined inclusion/exclusion criteria may apply
研究组 & 干预措施
Canakinumab
Eligible participants were assigned to receive canakinumab in one of four cohorts; 1) Single IV infusion of canakinumab 0.3 mg/kg; 2) Singe IV infusion of canakinumab 10 mg/kg; 3) single IV infusion of canakinumab 0.1 mg/kg or 0.3 mg/kg, or 1.5 mg/kg; 4) Single IV injection of canakinumab 0.03 mg/kg.
All participants were required to take a concomitant stable daily dose of metformin during the study.
干预措施: Canakinumab (Drug)
Canakinumab
Eligible participants were assigned to receive canakinumab in one of four cohorts; 1) Single IV infusion of canakinumab 0.3 mg/kg; 2) Singe IV infusion of canakinumab 10 mg/kg; 3) single IV infusion of canakinumab 0.1 mg/kg or 0.3 mg/kg, or 1.5 mg/kg; 4) Single IV injection of canakinumab 0.03 mg/kg.
All participants were required to take a concomitant stable daily dose of metformin during the study.
干预措施: Metformin (Drug)
Placebo
Eligible participants were assigned to receive placebo to canakinumab in one of four cohorts; 1) Single IV infusion of placebo to canakinumab 0.3 mg/kg; 2) Singe IV infusion of placebo to canakinumab 10 mg/kg; 3) single IV infusion of placebo to canakinumab 0.1 mg/kg or 0.3 mg/kg, or 1.5 mg/kg; 4) Single IV injection of placebo to canakinumab 0.03 mg/kg.
All participants were required to take a concomitant stable daily dose of metformin during the study.
干预措施: Placebo (Drug)
Placebo
Eligible participants were assigned to receive placebo to canakinumab in one of four cohorts; 1) Single IV infusion of placebo to canakinumab 0.3 mg/kg; 2) Singe IV infusion of placebo to canakinumab 10 mg/kg; 3) single IV infusion of placebo to canakinumab 0.1 mg/kg or 0.3 mg/kg, or 1.5 mg/kg; 4) Single IV injection of placebo to canakinumab 0.03 mg/kg.
All participants were required to take a concomitant stable daily dose of metformin during the study.
干预措施: Metformin (Drug)
结局指标
主要结局
Mean Change From Baseline in Plasma HbA1c (Glycosylated Hemoglobin / Hemoglobin A1c)
时间窗: Baseline, Day 28, Day 84, Day 126, End of Study (168 [+/- 5] days after dosing)
Blood was drawn after an overnight fast to measure plasma HbA1c levels. End of Study is defined as the last Analysis of covariance with treatment as a fixed effect and baseline as the covariate was performed.
Mean Change From Baseline in Plasma Glucose Area Under the Curve (AUC) 0 - 4 Hours Following Oral Glucose Tolerance Test (OGTT )
时间窗: Baseline, Day 28, Day 84
Mean Change in Glucose level stimulated by OGTT. Blood samples were taken at sample times: -20, -10, -1 and 10, 20, 30, 60, 90, 120, 180, and 240 minutes. Glucose levels over 4 hrs were shown as Area Under the Curve, (AUC). Analysis of covariance with treatment as a fixed effect and baseline as the covariate was performed.
次要结局
- Mean Change From Baseline in Plasma C-peptide AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test (OGTT)(Baseline, Day 28, Day 84)
- Mean Change From Baseline in Plasma Insulin AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test ( OGTT )(Baseline, Day 28, Day 84)
- Mean Change From Baseline in Plasma Proinsulin AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test ( OGTT )(Baseline, Day 28, Day 84)
- Mean Change From Baseline in Plasma Glucagon AUC ( Area Under the Curve) 0-4 Hours, Following Oral Glucose Tolerance Test(Baseline, Day 28, Day 84)
- Mean Change From Baseline in Peak Plasma Insulin/Proinsulin Level, Following Oral Glucose Tolerance Test (OGTT)(Baseline, Day 28, Day 84)
- Mean Insulin Secretion Rate ( ISR ) Relative to Glucose, 0 - 4 Hours(Day 28, Day 84)
- Mean Insulin Secretion Rate ( ISR ), 0 - 4 Hours(Day 28, Day 84)
- Insulin Sensitivity Index ( ISI ) at Day 28, Day 48(Day 28, Day 84)
- Insulinogenic Index, 0 - 30 Minutes(Day 28, Day 84)
- Mean Change From Baseline in Peak Plasma Glucose Following Oral Glucose Tolerance Test ( OGTT )(Baseline, Day 28, Day 84)
- Mean Change From Baseline in Peak Plasma Fructosamine Level(Baseline, Day 14, Day 28, Day 56, Day 84, Day 126, End of Study (168 [+/- 5] days after dosing))
- Insulin Resistance as Measured by the Homeostatic Model Assessment (HOMA-IR)(Baseline, Day 28, Day 84)
- β-cell Function as Measured by the Homeostatic Model Assessment (HOMA-β )(Baseline, Day 28, Day 84)
- Number of Participants Reporting Death, Serious Adverse Events (SAEs), Adverse Events (AE) Above 5% Frequency(Baseline to End of Study (56[+/-2] and 168 [+/- 5] days after dosing for Cohort 1 and Cohorts 2-4, respectively))