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
This study has been completed.
Sponsor:
Novartis
Information provided by:
Novartis
ClinicalTrials.gov Identifier:
NCT01068860
First received: February 12, 2010
Last updated: August 3, 2011
Last verified: August 2011
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Type 2 Diabetes Mellitus Impaired Glucose Tolerance |
Drug: Canakinumab 150 mg Drug: Placebo to Canakinumab |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
| Official Title: | 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 |
Resource links provided by NLM:
Drug Information available for:
Tolbutamide
Chlorpropamide
Metformin
Metformin hydrochloride
Tolazamide
Glyburide
Insulin human
Dextrose
Glipizide
Glimepiride
Insulin lispro
Canakinumab
U.S. FDA Resources
Further study details as provided by Novartis:
Primary Outcome Measures:
- Mean Change in Meal Stimulated Insulin Secretion Rate (ISR) Relative to Glucose 0-2 Hours, From Baseline to 4 Weeks. [ Time Frame: Baseline, 4 weeks ] [ Designated as safety issue: No ]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:
- Mean Change in Meal Stimulated Insulin Secretion Rate (ISR) Relative to Glucose 2-4 Hours, From Baseline to 4 Weeks [ Time Frame: Baseline, 4 weeks ] [ Designated as safety issue: No ]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. [ Time Frame: Baseline, 4 weeks ] [ Designated as safety issue: No ]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 [ Time Frame: Baseline, 4 weeks ] [ Designated as safety issue: No ]
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 population
- Mean Change in Fructosamine, From Baseline to 4 Weeks [ Time Frame: Baseline, 4 weeks ] [ Designated as safety issue: No ]
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 population
- Mean Change in Fasting Plasma Insulin, From Baseline to 4 Weeks [ Time Frame: Baseline, 4 weeks ] [ Designated as safety issue: No ]
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 population
- Mean Change in Quantitative Insulin Sensitivity Check Index (QUICKI) Score, From Baseline to 4 Weeks [ Time Frame: Baseline, 4 weeks ] [ Designated as safety issue: No ]
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 [ Time Frame: Baseline, 4 weeks ] [ Designated as safety issue: No ]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 [ Time Frame: Baseline, 4 weeks ] [ Designated as safety issue: No ]
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 [ Time Frame: Baseline, 4 weeks ] [ Designated as safety issue: No ]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 [ Time Frame: Baseline, 4 weeks ] [ Designated as safety issue: No ]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 [ Time Frame: Baseline, 4 weeks ] [ Designated as safety issue: No ]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 [ Time Frame: Baseline, 4 weeks ] [ Designated as safety issue: No ]
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 [ Time Frame: Baseline, 4 weeks ] [ Designated as safety issue: No ]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 [ Time Frame: Baseline, 4 weeks ] [ Designated as safety issue: Yes ]
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 [ Time Frame: Baseline, 4 weeks ] [ Designated as safety issue: Yes ]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.
| Enrollment: | 246 |
| Study Start Date: | February 2010 |
| Study Completion Date: | August 2010 |
| Primary Completion Date: | August 2010 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: 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
|
Drug: Canakinumab 150 mg
Single subcutaneous injection of Canakinumab 150 mg.
Other Names:
|
|
Placebo Comparator: 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
|
Drug: Placebo to Canakinumab
Single subcutaneous injection of Placebo to Canakinumab.
Other Names:
|
|
Experimental: 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.
|
Drug: Canakinumab 150 mg
Single subcutaneous injection of Canakinumab 150 mg.
Other Names:
|
|
Placebo Comparator: 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.
|
Drug: Placebo to Canakinumab
Single subcutaneous injection of Placebo to Canakinumab.
Other Names:
|
|
Experimental: 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.
|
Drug: Canakinumab 150 mg
Single subcutaneous injection of Canakinumab 150 mg.
Other Names:
|
|
Placebo Comparator: 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.
|
Drug: Placebo to Canakinumab
Single subcutaneous injection of Placebo to Canakinumab.
Other Names:
|
|
Experimental: 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
|
Drug: Canakinumab 150 mg
Single subcutaneous injection of Canakinumab 150 mg.
Other Names:
|
|
Placebo Comparator: 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
|
Drug: Placebo to Canakinumab
Single subcutaneous injection of Placebo to Canakinumab.
Other Names:
|
|
Experimental: 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.
|
Drug: Canakinumab 150 mg
Single subcutaneous injection of Canakinumab 150 mg.
Other Names:
|
|
Placebo Comparator: 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.
|
Drug: Placebo to Canakinumab
Single subcutaneous injection of Placebo to Canakinumab.
Other Names:
|
Eligibility| Ages Eligible for Study: | 18 Years to 74 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
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
Exclusion Criteria:
- 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.
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01068860
Hide Study Locations
Hide Study LocationsLocations
| United States, California | |
| National Research Institute | |
| Los Angeles, California, United States | |
| Crest Clinical Trials | |
| Santa Ana, California, United States | |
| Encompass Clinical Research | |
| Spring Valley, California, United States | |
| United States, Kentucky | |
| Commonwealth Biomedical Research LLC | |
| Madisonville, Kentucky, United States | |
| United States, Nebraska | |
| VA Medical Center | |
| Omaha, Nebraska, United States | |
| University of Nebraska Medical Center | |
| Omaha, Nebraska, United States | |
| United States, North Dakota | |
| Lillestol Research LLC | |
| Fargo, North Dakota, United States | |
| United States, Pennsylvania | |
| Preferred Primary Care Physicians | |
| Pittsburgh, Pennsylvania, United States | |
| United States, Texas | |
| Dallas Diabetes and Endocrine Center | |
| Dallas, Texas, United States | |
| Texas Center for Drug Development P.A. | |
| Houston, Texas, United States | |
| United States, Utah | |
| Utah Clinical Trials | |
| Salt Lake City, Utah, United States | |
| Australia, Victoria | |
| Barwon Health - Geelong Hospital | |
| Geelong, Victoria, Australia | |
| Austin Health - Heidelberg Repatriation Hospital | |
| Heidelberg Heights, Victoria, Australia | |
| Melbourne Health - Royal Melbourne Hospital | |
| Melbourne, Victoria, Australia | |
| Canada, Ontario | |
| Lifestyle Metabolism Centre (Etobicoke) | |
| Etobicoke, Ontario, Canada | |
| LMC Endocrinology Centres (Markham) Ltd | |
| Markham, Ontario, Canada | |
| LMC Endocrinology Centres (Thornhill) Ltd | |
| Thornhill, Ontario, Canada | |
| Canada, Quebec | |
| Centre de recherche clinique de Laval | |
| Laval, Quebec, Canada | |
| Hôpital Maisonneuve-Rosemont | |
| Montreal, Quebec, Canada | |
| Finland | |
| Lihavuustutkimusyksikkö | |
| Helsinki, Finland | |
| Lääkärikeskus Mehiläinen Töölö | |
| Helsinki, Finland | |
| ODL Terveys Oy | |
| Oulu, Finland | |
| Germany | |
| Clintrial Berlin Praxis fuer medizinische Studien | |
| Berlin, Germany | |
| Klinische Forschung Berlin-Buch Dr. Andrei Khariouzov | |
| Berlin, Germany | |
| "Sana Krankenhaus Gerresheim | |
| Duesseldorf, Germany | |
| Gemeinschaftspraxis Dr. Ingo Zeissig | |
| Duisburg, Germany | |
| Praxis Dr. Thorsten Rau | |
| Essen, Germany | |
| Praxis Dr. med. Joerg Luedemann | |
| Falkensee, Germany | |
| Dr. Helmut Anderten Gemeinschaftspraxis Dres. Anderten und Krok | |
| Hildesheim, Germany | |
| Praxis Dr. Julia Chevts | |
| Karlsruhe, Germany | |
| Pro Scientia Med | |
| Luebeck, Germany | |
| Praxis Dr. Winfried Keuthage | |
| Muenster, Germany | |
| Praxis Dr. Uwe Boeckmann | |
| Neumuenster, Germany | |
| Dr. Klaus Funke IkFE Studiencenter Potsdam GMBH I.G. | |
| Potsdam, Germany | |
| Praxis Dr. Gerhard Steinmaier | |
| Viernheim, Germany | |
| Praxis Dr. Reinhold U. Schneider | |
| Wetzlar-Naunheim, Germany | |
| India | |
| Visakha Diabetes & Endocrine Centre | |
| Visakhapatnam, AP, India | |
| Jnana Sanjeevini Medical Center | |
| Bangalore, Kar, India | |
| Bangalore Diabetes Hospital, | |
| Banglore, KAR, India | |
| Health & Research Centre | |
| Trivandrum, Ker, India | |
| Indrayani Speciality Hospital, | |
| Nagpur, Maharastra, India | |
| Sahyadri Hospital Bibewewadi Centre of Excellence for Diabetics | |
| Pune, Mah, India | |
| Diabetes Thyroid Hormone Research Institute Pvt .Ltd. | |
| Indore, MP, India | |
| Madras Diabetes Research Foundation | |
| Chennai, TN, India | |
| Italy | |
| Azienda Ospedaliera-Ospedali Riuniti di BergamoU | |
| Bergamo, BG, Italy | |
| Az. Ospedaliera Universit. S.Martino-Universita degli Studi | |
| Genova, GE, Italy | |
| 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 | |
| A.O.Universitaria Senese, Universita degli Studi di Siena | |
| Siena, SI, Italy | |
| S.C.D.U. Endocrinologia e Malattie del Metabolismo | |
| Torino, To, Italy | |
| Policlinico A.Gemelli - Univ.Cattolica del Sacro Cuore | |
| Roma, Italy | |
Sponsors and Collaborators
Novartis
Investigators
| Study Director: | Novartis Pharmaceuticals Corporation | Novartis Pharmaceuticals |
More Information
No publications provided
| Responsible Party: | External Affairs, Novartis Pharmaceuticals |
| ClinicalTrials.gov Identifier: | NCT01068860 History of Changes |
| Other Study ID Numbers: | CACZ885I2207 |
| Study First Received: | February 12, 2010 |
| Results First Received: | August 3, 2011 |
| Last Updated: | August 3, 2011 |
| Health Authority: | Australia: Department of Health and Ageing Therapeutic Goods Administration Canada: Health Canada Finland: Finnish Medicines Agency Germany: Federal Institute for Drugs and Medical Devices India: Drugs Controller General of India Italy: The Italian Medicines Agency United States: Food and Drug Administration |
Keywords provided by Novartis:
|
Type 2 Diabetes Mellitus canakinumab Pre diabetic glucose intolerant |
oral anti diabetic medication insulin treatment metabolic syndrome |
Additional relevant MeSH terms:
|
Diabetes Mellitus Diabetes Mellitus, Type 2 Glucose Intolerance Glucose Metabolism Disorders Metabolic Diseases Endocrine System Diseases Hyperglycemia Troglitazone Glimepiride 2,4-thiazolidinedione Acetohexamide Chlorpropamide Glyburide Glipizide |
Insulin Metformin Tolazamide Tolbutamide Antibodies, Monoclonal Hypoglycemic Agents Physiological Effects of Drugs Pharmacologic Actions Immunosuppressive Agents Immunologic Factors Anti-Arrhythmia Agents Cardiovascular Agents Therapeutic Uses |
ClinicalTrials.gov processed this record on May 21, 2013