A Multi-center, Double-blind, Placebo-controlled, Randomized Study to Compare the Effect of a Subcutaneous Canakinumab Administration to Placebo in Patients With Impaired Glucose Tolerance or Patients With Type 2 Diabetes Treated With Differing Baseline Diabetes Therapies
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Novartis
- 入组人数
- 246
- 试验地点
- 52
- 主要终点
- Mean Change in Meal Stimulated Insulin Secretion Rate (ISR) Relative to Glucose 0-2 Hours, From Baseline to 4 Weeks.
研究概览
简要总结
This was a 10-week, placebo-controlled, randomized study to investigate the effect of injectable IL-1B antagonist, Canakinumab , in participants with impaired glucose tolerance or Type 2 Diabetes Mellitus (T2DM) already treated on different background diabetes therapies.
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
- 18 Years 至 74 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient must fulfill all criteria in one of the following groups:
- •Impaired Glucose Tolerance (IGT) as diagnosed per protocol and not on an anti-diabetic medicine during the study
- •Diagnosis of Type 2 diabetes in stable treatment with metformin
- •Diagnosis of Type 2 diabetes in stable treatment with metformin (at least 1000 mg/day) in combination with a sulfonylurea
- •Diagnosis of Type 2 diabetes in stable treatment with metformin (at least 1000 mg/day), sulfonylurea and thiazolidinedione combination therapy
- •Diagnosis of Type 2 diabetes in stable treatment with at least two insulin injections a day with or without metformin
- •HbA1c between 6.5% and 8%, inclusive, at Screening; this criterion does not apply to the IGT group
- •Age from 18-74 years, inclusive, and of either sex
排除标准
- •Type 1 diabetes or diabetes that is a result of pancreatic injury or other secondary forms of diabetes
- •History or current findings of active pulmonary disease (e.g. tuberculosis, fungal diseases) as defined in the protocol:
- •Known presence or suspicion of active or recurrent bacterial, fungal or viral infection at the time of enrollment proven.
研究组 & 干预措施
Canakinumab 150 mg + Metformin
Eligible participants received a single subcutaneous injection Canakinumab 150 mg.Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) monotherapy treatment at least 1000 mg/day for 3 months prior to screening
干预措施: Canakinumab 150 mg (Drug)
Placebo + Metformin
Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) monotherapy treatment at least 1000 mg/day for 3 months prior to screening
干预措施: Placebo to Canakinumab (Drug)
Canakinumab 150 mg + Metforimin + Sulfonylurea
Eligible participants received a single subcutaneous injection of Canakinumab 150 mg.Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.
干预措施: Canakinumab 150 mg (Drug)
Placebo + Metforimin + Sulfonylurea
Eligible participants received a single subcutaneous injection of Placebo to Canakinumab.Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.
干预措施: Placebo to Canakinumab (Drug)
Canakinumab 150 mg + Met + Sulfonyl + Thiazolidinedione
Eligible participants received a single subcutaneous injection of Canakinumab 150 mg.Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose, and a Thiazolidinedione (Thiaz)at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.
干预措施: Canakinumab 150 mg (Drug)
Placebo + Met + Sulfonyl + Thiazolidinedione
Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus and be on a stable dose of Metformin (Met) at least 1000 mg/day , and a Sulfonylurea (Sulfonyl), at least 1/2 the maximally labeled dose, and a Thiazolidinedione (Thiaz)at least 1/2 the maximally labeled dose combination therapy, for 3 months prior to screening.
干预措施: Placebo to Canakinumab (Drug)
Canakinumab 150 mg + Insulin
Eligible participants received a single subcutaneous injection of Canakinumab 150 mg. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus for 3 months prior to screening and be on a stable dose of Insulin, 2 insulin injections per day for a total daily dose of less than 100 U with or without Metformin (Met)for 3 months prior to screening
干预措施: Canakinumab 150 mg (Drug)
Placebo + Insulin
Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had documented diagnosis of Type 2 Diabetes Mellitus for 3 months prior to screening and be on a stable dose of Insulin, 2 insulin injections per day for a total daily dose of less than 100 U with or without Metformin (Met)for 3 months prior to screening
干预措施: Placebo to Canakinumab (Drug)
Canakinumab 150 mg in patients with IGT
Eligible participants received a single subcutaneous injection of Canakinumab 150 mg. Patients must have had Impaired Glucose Tolerance (IGT) as defined by the World Health Organization (WHO) criteria confirmed at screening visit.
干预措施: Canakinumab 150 mg (Drug)
Placebo in patients with IGT
Eligible participants received a single subcutaneous injection of Placebo to Canakinumab. Patients must have had Impaired Glucose Tolerance (IGT) as defined by the World Health Organization (WHO) criteria confirmed at screening visit.
干预措施: Placebo to Canakinumab (Drug)
结局指标
主要结局
Mean Change in Meal Stimulated Insulin Secretion Rate (ISR) Relative to Glucose 0-2 Hours, From Baseline to 4 Weeks.
时间窗: Baseline, 4 weeks
Change in Insulin Secretion Rate stimulated by Liquid mixed-meal challenge. Blood samples were taken prior to and after meal for glucose and insulin at sample times: -20, -10, -1 and 10, 20, 30, 60, 90, 120, 180, and 240 minutes relative to the start of the meal.A mixed model with treatment fitted as fixed effect, and population and the interaction of population and treatment fitted as random effects were used for the comparison of Canakinumab versus placebo within each T2DM population. The mixed model did not include patients from the IGT population
次要结局
- Mean Change in Meal Stimulated Insulin Secretion Rate (ISR) Relative to Glucose 2-4 Hours, From Baseline to 4 Weeks(Baseline, 4 weeks)
- Mean Change in Meal Stimulated Insulin Secretion Rate (ISR) Relative to Glucose 0-4 Hours, From Baseline to 4 Weeks.(Baseline, 4 weeks)
- Mean Change in Fasting Plasma Glucose, From Baseline to 4 Weeks(Baseline, 4 weeks)
- Mean Change in Fructosamine, From Baseline to 4 Weeks(Baseline, 4 weeks)
- Mean Change in Fasting Plasma Insulin, From Baseline to 4 Weeks(Baseline, 4 weeks)
- Mean Change in Quantitative Insulin Sensitivity Check Index (QUICKI) Score, From Baseline to 4 Weeks(Baseline, 4 weeks)
- Mean Change in Fasting Glucose Disposition Index(GDI)1 and Index 2, From Baseline to 4 Weeks(Baseline, 4 weeks)
- Mean Change in Absolute Glucose Level at 2 Hours, From Baseline to 4 Weeks(Baseline, 4 weeks)
- Mean Change in Insulin Area Under the Curve (AUC) 0-4 Hours, From Baseline to 4 Weeks(Baseline, 4 weeks)
- Mean Change in C-peptide Area Under the Curve (AUC), 0-4 Hours, From Baseline to 4 Weeks(Baseline, 4 weeks)
- Mean Change in Post-prandial Glucose Area Under the Curve (AUC)0-4 Hours, From Baseline to 4 Weeks(Baseline, 4 weeks)
- Mean Change in Peak Plasma Glucose, From Baseline to 4 Weeks(Baseline, 4 weeks)
- Mean Change in Peak Plasma Insulin, From Baseline to 4 Weeks(Baseline, 4 weeks)
- Mean Change in Peak Plasma C-peptide Level, From Baseline to 4 Weeks(Baseline, 4 weeks)
- Number of Participants Reporting Death, Serious Adverse Events (SAEs) and Adverse Events (AEs) Above 5% Frequency, From Baseline to 4 Weeks(Baseline, 4 weeks)