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

Type 2 Diabetes Mellitus Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01068860
• Other study ID #: CACZ885I2207
• Status: Completed
• Phase: Phase 2
• First received: February 12, 2010
• Last updated: August 3, 2011
• Start date: February 2010
• Est. completion date: August 2010

Study information

• Verified date: August 2011
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Department of Health and Ageing Therapeutic Goods AdministrationCanada: Health CanadaFinland: Finnish Medicines AgencyGermany: Federal Institute for Drugs and Medical DevicesIndia: Drugs Controller General of IndiaItaly: The Italian Medicines AgencyUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 246
• Est. completion date: August 2010
• Est. primary completion date: August 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 74 Years

Eligibility

Inclusion Criteria:

1. 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

2. HbA1c between 6.5% and 8%, inclusive, at Screening; this criterion does not apply to the IGT group

3. Age from 18-74 years, inclusive, and of either sex

Exclusion Criteria:

1. Type 1 diabetes or diabetes that is a result of pancreatic injury or other secondary forms of diabetes

2. History or current findings of active pulmonary disease (e.g. tuberculosis, fungal diseases) as defined in the protocol:

3. Known presence or suspicion of active or recurrent bacterial, fungal or viral infection at the time of enrollment proven.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Glucose Intolerance
• Impaired Glucose Tolerance
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Canakinumab 150 mg
Single subcutaneous injection of Canakinumab 150 mg.
• Placebo to Canakinumab
Single subcutaneous injection of Placebo to Canakinumab.

Locations

Country	Name	City	State
Australia	Barwon Health - Geelong Hospital	Geelong	Victoria
Australia	Austin Health - Heidelberg Repatriation Hospital	Heidelberg Heights	Victoria
Australia	Melbourne Health - Royal Melbourne Hospital	Melbourne	Victoria
Canada	Lifestyle Metabolism Centre (Etobicoke)	Etobicoke	Ontario
Canada	Centre de recherche clinique de Laval	Laval	Quebec
Canada	LMC Endocrinology Centres (Markham) Ltd	Markham	Ontario
Canada	Hôpital Maisonneuve-Rosemont	Montreal	Quebec
Canada	LMC Endocrinology Centres (Thornhill) Ltd	Thornhill	Ontario
Finland	Lääkärikeskus Mehiläinen Töölö	Helsinki
Finland	Lihavuustutkimusyksikkö	Helsinki
Finland	ODL Terveys Oy	Oulu
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
India	Jnana Sanjeevini Medical Center	Bangalore	Kar
India	Bangalore Diabetes Hospital,	Banglore	KAR
India	Madras Diabetes Research Foundation	Chennai	TN
India	Diabetes Thyroid Hormone Research Institute Pvt .Ltd.	Indore	MP
India	Indrayani Speciality Hospital,	Nagpur	Maharastra
India	Sahyadri Hospital Bibewewadi Centre of Excellence for Diabetics	Pune	Mah
India	Health & Research Centre	Trivandrum	Ker
India	Visakha Diabetes & Endocrine Centre	Visakhapatnam	AP
Italy	Azienda Ospedaliera-Ospedali Riuniti di BergamoU	Bergamo	BG
Italy	Az. Ospedaliera Della Prov.di Pavia	Casorate Primo	PV
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	Policlinico A.Gemelli - Univ.Cattolica del Sacro Cuore	Roma
Italy	A.O.Universitaria Senese, Universita degli Studi di Siena	Siena	SI
Italy	S.C.D.U. Endocrinologia e Malattie del Metabolismo	Torino	To
United States	Dallas Diabetes and Endocrine Center	Dallas	Texas
United States	Lillestol Research LLC	Fargo	North Dakota
United States	Texas Center for Drug Development P.A.	Houston	Texas
United States	National Research Institute	Los Angeles	California
United States	Commonwealth Biomedical Research LLC	Madisonville	Kentucky
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	VA Medical Center	Omaha	Nebraska
United States	Preferred Primary Care Physicians	Pittsburgh	Pennsylvania
United States	Utah Clinical Trials	Salt Lake City	Utah
United States	Crest Clinical Trials	Santa Ana	California
United States	Encompass Clinical Research	Spring Valley	California

Sponsors (1)

Lead Sponsor	Collaborator
Novartis

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Finland,  Germany,  India,  Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean Change in Meal Stimulated Insulin Secretion Rate (ISR) Relative to Glucose 0-2 Hours, From Baseline to 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	Baseline, 4 weeks	No
Secondary	Mean Change in Meal Stimulated Insulin Secretion Rate (ISR) Relative to Glucose 2-4 Hours, From Baseline to 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	Baseline, 4 weeks	No
Secondary	Mean Change in Meal Stimulated Insulin Secretion Rate (ISR) Relative to Glucose 0-4 Hours, From Baseline to 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.	Baseline, 4 weeks	No
Secondary	Mean Change in Fasting Plasma Glucose, From Baseline to 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 population	Baseline, 4 weeks	No
Secondary	Mean Change in Fructosamine, From Baseline to 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 population	Baseline, 4 weeks	No
Secondary	Mean Change in Fasting Plasma Insulin, From Baseline to 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 population	Baseline, 4 weeks	No
Secondary	Mean Change in Quantitative Insulin Sensitivity Check Index (QUICKI) Score, From Baseline to 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.	Baseline, 4 weeks	No
Secondary	Mean Change in Fasting Glucose Disposition Index(GDI)1 and Index 2, From Baseline to 4 Weeks	GDI 1 is the product of insulin sensitivity index (Si)during the 1st phase of insulin secretion and ß-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 ß-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.	Baseline, 4 weeks	No
Secondary	Mean Change in Absolute Glucose Level at 2 Hours, From Baseline to 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.	Baseline, 4 weeks	No
Secondary	Mean Change in Insulin Area Under the Curve (AUC) 0-4 Hours, From Baseline to 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 SAx 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.	Baseline, 4 weeks	No
Secondary	Mean Change in C-peptide Area Under the Curve (AUC), 0-4 Hours, From Baseline to 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 SAx 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.	Baseline, 4 weeks	No
Secondary	Mean Change in Post-prandial Glucose Area Under the Curve (AUC)0-4 Hours, From Baseline to 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 SAx 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.	Baseline, 4 weeks	No
Secondary	Mean Change in Peak Plasma Glucose, From Baseline to 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.	Baseline, 4 weeks	No
Secondary	Mean Change in Peak Plasma Insulin, From Baseline to 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.	Baseline, 4 weeks	No
Secondary	Mean Change in Peak Plasma C-peptide Level, From Baseline to 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.	Baseline, 4 weeks	Yes
Secondary	Number of Participants Reporting Death, Serious Adverse Events (SAEs) and Adverse Events (AEs) Above 5% Frequency, From Baseline to 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.	Baseline, 4 weeks	Yes