To Compare the Effect of a Subcutaneous Canakinumab Administration to Placebo in Patients With Impaired Glucose Tolerance or Patients With Type 2 Diabetes With Differing Baseline Diabetes Therapies
- Conditions
- Type 2 Diabetes MellitusImpaired Glucose Tolerance
- Interventions
- Registration Number
- NCT01068860
- Lead Sponsor
- Novartis
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 246
-
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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Canakinumab 150 mg + Metforimin + Sulfonylurea Canakinumab 150 mg 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. Canakinumab 150 mg + Met + Sulfonyl + Thiazolidinedione Canakinumab 150 mg 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. Canakinumab 150 mg + Metformin Canakinumab 150 mg 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 Canakinumab 150 mg in patients with IGT Canakinumab 150 mg 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. Placebo in patients with IGT Placebo to Canakinumab 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. Placebo + Metformin Placebo to Canakinumab 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 Placebo + Metforimin + Sulfonylurea Placebo to Canakinumab 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. Placebo + Met + Sulfonyl + Thiazolidinedione Placebo to Canakinumab 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. Canakinumab 150 mg + Insulin Canakinumab 150 mg 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 Placebo + Insulin Placebo to Canakinumab 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
- Primary Outcome Measures
Name Time Method Mean Change in Meal Stimulated Insulin Secretion Rate (ISR) Relative to Glucose 0-2 Hours, From Baseline to 4 Weeks. 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
- Secondary Outcome Measures
Name Time Method Mean Change in Meal Stimulated Insulin Secretion Rate (ISR) Relative to Glucose 2-4 Hours, From Baseline to 4 Weeks 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 participants from the IGT population
Mean Change in Meal Stimulated Insulin Secretion Rate (ISR) Relative to Glucose 0-4 Hours, From Baseline to 4 Weeks. 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, insulin and C-peptide 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 participants from the IGT population.
Mean Change in Fasting Plasma Glucose, From Baseline to 4 Weeks Baseline, 4 weeks Change in Fasting Glucose Level measured from plasma taken at Baseline and after 4 weeks of treatment.
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 participants from the IGT populationMean Change in Fructosamine, From Baseline to 4 Weeks Baseline, 4 weeks Change in Fructosamine Level taken from plasma, measured at Baseline and after 4 weeks of treatment.
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 participants from the IGT populationMean Change in Fasting Plasma Insulin, From Baseline to 4 Weeks Baseline, 4 weeks Change in Fasting Insulin level taken from plasma, measured at Baseline and after 4 weeks of treatment.
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 participants from the IGT populationMean Change in Quantitative Insulin Sensitivity Check Index (QUICKI) Score, From Baseline to 4 Weeks Baseline, 4 weeks The Quantitative Insulin Sensitivity Check Index (QUICKI) score, measures insulin sensitivity which is the inverse of insulin resistance. The score is calculated by the equation: 1 /(log(fasting insulin µU/mL) + log(fasting glucose mg/dL)). In normal subjects the mean score ± SE is 0.366 ± 0.029.
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 participants from the IGT population.Mean Change in Fasting Glucose Disposition Index(GDI)1 and Index 2, From Baseline to 4 Weeks Baseline, 4 weeks GDI 1 is the product of insulin sensitivity index (Si)during the 1st phase of insulin secretion and β-cell function as measured by the acute insulin response (AIR).GDI 2 is the product of (Si)during the 2nd phase of insulin secretion and β-cell function as measured by the acute insulin response (AIR). 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 participants from the IGT group.
Mean Change in Absolute Glucose Level at 2 Hours, From Baseline to 4 Weeks Baseline, 4 weeks Change in glucose level measured after 2 hours of fasting. Blood sample was drawn at 0 minutes and at 240 minutes.
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 participants from the IGT population.Mean Change in Insulin Area Under the Curve (AUC) 0-4 Hours, From Baseline to 4 Weeks Baseline, 4 weeks Blood samples were drawn after a test meal at 0, 15, 30, 45, 60, 90, 120, 180 and 240 min. Insulin levels over 4 hrs were shown as Area Under the Curve,(AUC). AUC was calculated as: x=1 AUC ΣAx n Where Ax = AUC for the 240 min.interval, and X = 1 for the 1st interval. 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 vs placebo within each T2DM group. The mixed model didn't include the IGT group.
Mean Change in C-peptide Area Under the Curve (AUC), 0-4 Hours, From Baseline to 4 Weeks Baseline, 4 weeks Blood samples were drawn after a test meal at 0, 15, 30, 45, 60, 90, 120, 180 and 240 min. Insulin levels over 4 hrs were shown as Area Under the Curve,(AUC). AUC was calculated as: x=1 AUC ΣAx n Where Ax = AUC for the 240 min.interval, and X = 1 for the 1st interval. 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 vs placebo within each T2DM group. The mixed model didn't include the IGT group.
Mean Change in Post-prandial Glucose Area Under the Curve (AUC)0-4 Hours, From Baseline to 4 Weeks Baseline, 4 weeks Blood samples were drawn after a test meal at 0, 15, 30, 45, 60, 90, 120, 180 and 240 min. Insulin levels over 4 hrs were shown as Area Under the Curve,(AUC). AUC was calculated as: x=1 AUC ΣAx n Where Ax = AUC for the 240 min.interval, and X = 1 for the 1st interval. 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 vs placebo within each T2DM group. The mixed model didn't include the IGT group.
Mean Change in Peak Plasma Glucose, From Baseline to 4 Weeks Baseline, 4 weeks Change in peak plasma glucose level as measured from Baseline to 4 weeks of treatment.
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 participants from the IGT population.Mean Change in Peak Plasma Insulin, From Baseline to 4 Weeks Baseline, 4 weeks Change in mean peak plasma Insulin level as measured from Baseline to 4 weeks of treatment. 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 participants from the IGT population.
Mean Change in Peak Plasma C-peptide Level, From Baseline to 4 Weeks Baseline, 4 weeks Change in mean peak plasma C-peptide level measured from Baseline to 4 weeks of treatment.
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 participants from the IGT population.Number of Participants Reporting Death, Serious Adverse Events (SAEs) and Adverse Events (AEs) Above 5% Frequency, From Baseline to 4 Weeks Baseline, 4 weeks An adverse event is any unwanted event, whether related to study drug or not occuring during the study period. A Serious Adverse Event (SAE) is an event resulting in death, requiring or prolonging hospitalization, a congenital anomaly or other important medical event. AEs and SAEs were recorded at each visit.
Trial Locations
- Locations (52)
Commonwealth Biomedical Research LLC
🇺🇸Madisonville, Kentucky, United States
LMC Endocrinology Centres (Markham) Ltd
🇨🇦Markham, Ontario, Canada
ODL Terveys Oy
🇫🇮Oulu, Finland
Crest Clinical Trials
🇺🇸Santa Ana, California, United States
Utah Clinical Trials
🇺🇸Salt Lake City, Utah, United States
Praxis Dr. med. Joerg Luedemann
🇩🇪Falkensee, Germany
Hôpital Maisonneuve-Rosemont
🇨🇦Montreal, Quebec, Canada
Dr. Helmut Anderten Gemeinschaftspraxis Dres. Anderten und Krok
🇩🇪Hildesheim, Germany
Gemeinschaftspraxis Dr. Ingo Zeissig
🇩🇪Duisburg, Germany
Texas Center for Drug Development P.A.
🇺🇸Houston, Texas, United States
Lihavuustutkimusyksikkö
🇫🇮Helsinki, Finland
Dallas Diabetes and Endocrine Center
🇺🇸Dallas, Texas, United States
Praxis Dr. Thorsten Rau
🇩🇪Essen, Germany
Praxis Dr. Julia Chevts
🇩🇪Karlsruhe, Germany
VA Medical Center
🇺🇸Omaha, Nebraska, United States
Lillestol Research LLC
🇺🇸Fargo, North Dakota, United States
Lifestyle Metabolism Centre (Etobicoke)
🇨🇦Etobicoke, Ontario, Canada
Centre de recherche clinique de Laval
🇨🇦Laval, Quebec, Canada
Pro Scientia Med
🇩🇪Luebeck, Germany
Praxis Dr. Winfried Keuthage
🇩🇪Muenster, Germany
Dr. Klaus Funke IkFE Studiencenter Potsdam GMBH I.G.
🇩🇪Potsdam, Germany
Azienda Ospedaliera S. Paolo-Polo Universitario
🇮🇹Milano, MI, Italy
Fondazione Centro San Raffaele del Monte Tabor-IRCCSUnità
🇮🇹Milano, Mi, Italy
Az. Ospedaliera Della Prov.di Pavia
🇮🇹Casorate Primo, PV, Italy
Azienda Ospedaliera-Ospedali Riuniti di BergamoU
🇮🇹Bergamo, BG, Italy
Praxis Dr. Uwe Boeckmann
🇩🇪Neumuenster, Germany
Praxis Dr. Reinhold U. Schneider
🇩🇪Wetzlar-Naunheim, Germany
LMC Endocrinology Centres (Thornhill) Ltd
🇨🇦Thornhill, Ontario, Canada
Clintrial Berlin Praxis fuer medizinische Studien
🇩🇪Berlin, Germany
Encompass Clinical Research
🇺🇸Spring Valley, California, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
National Research Institute
🇺🇸Los Angeles, California, United States
Preferred Primary Care Physicians
🇺🇸Pittsburgh, Pennsylvania, United States
Melbourne Health - Royal Melbourne Hospital
🇦🇺Melbourne, Victoria, Australia
Klinische Forschung Berlin-Buch Dr. Andrei Khariouzov
🇩🇪Berlin, Germany
"Sana Krankenhaus Gerresheim
🇩🇪Duesseldorf, Germany
Praxis Dr. Gerhard Steinmaier
🇩🇪Viernheim, Germany
Az. Ospedaliera Universit. S.Martino-Universita degli Studi
🇮🇹Genova, GE, Italy
Policlinico A.Gemelli - Univ.Cattolica del Sacro Cuore
🇮🇹Roma, Italy
S.C.D.U. Endocrinologia e Malattie del Metabolismo
🇮🇹Torino, To, Italy
A.O.Universitaria Senese, Universita degli Studi di Siena
🇮🇹Siena, SI, Italy
Diabetes Thyroid Hormone Research Institute Pvt .Ltd.
🇮🇳Indore, MP, India
Jnana Sanjeevini Medical Center
🇮🇳Bangalore, Kar, India
Madras Diabetes Research Foundation
🇮🇳Chennai, TN, India
Lääkärikeskus Mehiläinen Töölö
🇫🇮Helsinki, Finland
Bangalore Diabetes Hospital,
🇮🇳Banglore, KAR, India
Barwon Health - Geelong Hospital
🇦🇺Geelong, Victoria, Australia
Visakha Diabetes & Endocrine Centre
🇮🇳Visakhapatnam, AP, India
Health & Research Centre
🇮🇳Trivandrum, Ker, India
Indrayani Speciality Hospital,
🇮🇳Nagpur, Maharastra, India
Sahyadri Hospital Bibewewadi Centre of Excellence for Diabetics
🇮🇳Pune, Mah, India
Austin Health - Heidelberg Repatriation Hospital
🇦🇺Heidelberg Heights, Victoria, Australia