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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01068860




Registration number
NCT01068860
Ethics application status
Date submitted
12/02/2010
Date registered
15/02/2010
Date last updated
5/09/2011

Titles & IDs
Public title
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
Scientific 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
Secondary ID [1] 0 0
CACZ885I2207
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 2 Diabetes Mellitus 0 0
Impaired Glucose Tolerance 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Diabetes
Metabolic and Endocrine 0 0 0 0
Metabolic disorders
Metabolic and Endocrine 0 0 0 0
Other metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Canakinumab 150 mg
Treatment: Drugs - Placebo to Canakinumab

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

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

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.

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.

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.

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.

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

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

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.

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.


Treatment: Drugs: Canakinumab 150 mg
Single subcutaneous injection of Canakinumab 150 mg.

Treatment: Drugs: Placebo to Canakinumab
Single subcutaneous injection of Placebo to Canakinumab.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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
Timepoint [1] 0 0
Baseline, 4 weeks
Secondary outcome [1] 0 0
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
Timepoint [1] 0 0
Baseline, 4 weeks
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
Baseline, 4 weeks
Secondary outcome [3] 0 0
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
Timepoint [3] 0 0
Baseline, 4 weeks
Secondary outcome [4] 0 0
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
Timepoint [4] 0 0
Baseline, 4 weeks
Secondary outcome [5] 0 0
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
Timepoint [5] 0 0
Baseline, 4 weeks
Secondary outcome [6] 0 0
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.
Timepoint [6] 0 0
Baseline, 4 weeks
Secondary outcome [7] 0 0
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.
Timepoint [7] 0 0
Baseline, 4 weeks
Secondary outcome [8] 0 0
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.
Timepoint [8] 0 0
Baseline, 4 weeks
Secondary outcome [9] 0 0
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.
Timepoint [9] 0 0
Baseline, 4 weeks
Secondary outcome [10] 0 0
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.
Timepoint [10] 0 0
Baseline, 4 weeks
Secondary outcome [11] 0 0
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.
Timepoint [11] 0 0
Baseline, 4 weeks
Secondary outcome [12] 0 0
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.
Timepoint [12] 0 0
Baseline, 4 weeks
Secondary outcome [13] 0 0
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.
Timepoint [13] 0 0
Baseline, 4 weeks
Secondary outcome [14] 0 0
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.
Timepoint [14] 0 0
Baseline, 4 weeks
Secondary outcome [15] 0 0
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.
Timepoint [15] 0 0
Baseline, 4 weeks

Eligibility
Key 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
Minimum age
18 Years
Maximum age
74 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Barwon Health - Geelong Hospital - Geelong
Recruitment hospital [2] 0 0
Austin Health - Heidelberg Repatriation Hospital - Heidelberg Heights
Recruitment hospital [3] 0 0
Melbourne Health - Royal Melbourne Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
- Geelong
Recruitment postcode(s) [2] 0 0
- Heidelberg Heights
Recruitment postcode(s) [3] 0 0
- Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Kentucky
Country [3] 0 0
United States of America
State/province [3] 0 0
Nebraska
Country [4] 0 0
United States of America
State/province [4] 0 0
North Dakota
Country [5] 0 0
United States of America
State/province [5] 0 0
Pennsylvania
Country [6] 0 0
United States of America
State/province [6] 0 0
Texas
Country [7] 0 0
United States of America
State/province [7] 0 0
Utah
Country [8] 0 0
Canada
State/province [8] 0 0
Ontario
Country [9] 0 0
Canada
State/province [9] 0 0
Quebec
Country [10] 0 0
Finland
State/province [10] 0 0
Helsinki
Country [11] 0 0
Finland
State/province [11] 0 0
Oulu
Country [12] 0 0
Germany
State/province [12] 0 0
Berlin
Country [13] 0 0
Germany
State/province [13] 0 0
Duesseldorf
Country [14] 0 0
Germany
State/province [14] 0 0
Duisburg
Country [15] 0 0
Germany
State/province [15] 0 0
Essen
Country [16] 0 0
Germany
State/province [16] 0 0
Falkensee
Country [17] 0 0
Germany
State/province [17] 0 0
Hildesheim
Country [18] 0 0
Germany
State/province [18] 0 0
Karlsruhe
Country [19] 0 0
Germany
State/province [19] 0 0
Luebeck
Country [20] 0 0
Germany
State/province [20] 0 0
Muenster
Country [21] 0 0
Germany
State/province [21] 0 0
Neumuenster
Country [22] 0 0
Germany
State/province [22] 0 0
Potsdam
Country [23] 0 0
Germany
State/province [23] 0 0
Viernheim
Country [24] 0 0
Germany
State/province [24] 0 0
Wetzlar-Naunheim
Country [25] 0 0
India
State/province [25] 0 0
AP
Country [26] 0 0
India
State/province [26] 0 0
Kar
Country [27] 0 0
India
State/province [27] 0 0
KAR
Country [28] 0 0
India
State/province [28] 0 0
Ker
Country [29] 0 0
India
State/province [29] 0 0
Maharastra
Country [30] 0 0
India
State/province [30] 0 0
Mah
Country [31] 0 0
India
State/province [31] 0 0
MP
Country [32] 0 0
India
State/province [32] 0 0
TN
Country [33] 0 0
Italy
State/province [33] 0 0
BG
Country [34] 0 0
Italy
State/province [34] 0 0
GE
Country [35] 0 0
Italy
State/province [35] 0 0
MI
Country [36] 0 0
Italy
State/province [36] 0 0
Mi
Country [37] 0 0
Italy
State/province [37] 0 0
PV
Country [38] 0 0
Italy
State/province [38] 0 0
SI
Country [39] 0 0
Italy
State/province [39] 0 0
To
Country [40] 0 0
Italy
State/province [40] 0 0
Roma

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT01068860
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals Corporation
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications