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:
Information provided by:
Novartis
ClinicalTrials.gov Identifier:
NCT01068860
First received: February 12, 2010
Last updated: August 3, 2011
Last verified: August 2011

February 12, 2010
August 3, 2011
February 2010
August 2010   (final data collection date for primary outcome measure)
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
Evaluate canakinumab effects on change from baseline of meal challenge derived insulin secretion rate relative to glucose at 4 weeks for each population [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01068860 on ClinicalTrials.gov Archive Site
  • 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.
  • Evaluate the effect on change from baseline of other meal challenge derived parameters, including insulin, glucose and other glycemic control parameters [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  • Provide information on canakinumab effects on improving glucose parameters in people with impaired glucose tolerance [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  • Assess safety and tolerability for all study populations [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
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
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

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.

Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Type 2 Diabetes Mellitus
  • Impaired Glucose Tolerance
  • Drug: Canakinumab 150 mg
    Single subcutaneous injection of Canakinumab 150 mg.
    Other Names:
    • ACZ885
    • Glucophage
    • Chlorpropramide
    • Diabinese
    • Acetohexamide
    • Dymelor
    • Tolazamise
    • Tolinase
    • Tolbutamise
    • Orinase
    • Glipizide
    • Glucotrol
    • Glimepiride
    • Amaryl
    • Glyburide
    • DiaBeta
    • Micronase
    • Glynase PresTab
    • Troglitazone
    • Rezulin
    • Insulin
    • Iletin
    • Novolin
    • Velosulin
    • Humalog
    • Humulin
    • Lente
    • Ultralente
    • NPH Iletin
  • Drug: Placebo to Canakinumab
    Single subcutaneous injection of Placebo to Canakinumab.
    Other Names:
    • ACZ885
    • Glucophage
    • Chlorpropramide
    • Diabinese
    • Acetohexamide
    • Dymelor
    • Tolazamise
    • Tolinase
    • Tolbutamise
    • Orinase
    • Glipizide
    • Glucotrol
    • Glimepiride
    • Amaryl
    • Glyburide
    • DiaBeta
    • Micronase
    • Glynase PresTab
    • Troglitazone
    • Rezulin
    • Insulin
    • Iletin
    • Novolin
    • Velosulin
    • Humalog
    • Humulin
    • Lente
    • Ultralente
    • NPH Iletin
  • 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
    Intervention: Drug: Canakinumab 150 mg
  • 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
    Intervention: Drug: Placebo to Canakinumab
  • 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.
    Intervention: Drug: Canakinumab 150 mg
  • 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.
    Intervention: Drug: Placebo to Canakinumab
  • 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.
    Intervention: Drug: Canakinumab 150 mg
  • 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.
    Intervention: Drug: Placebo to Canakinumab
  • 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
    Intervention: Drug: Canakinumab 150 mg
  • 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
    Intervention: Drug: Placebo to Canakinumab
  • 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.
    Intervention: Drug: Canakinumab 150 mg
  • 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.
    Intervention: Drug: Placebo to Canakinumab
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
246
August 2010
August 2010   (final data collection date for primary outcome measure)

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.
Both
18 Years to 74 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Australia,   Canada,   Finland,   Germany,   India,   Italy
 
NCT01068860
CACZ885I2207
No
External Affairs, Novartis Pharmaceuticals
Novartis
Not Provided
Study Director: Novartis Pharmaceuticals Corporation Novartis Pharmaceuticals
Novartis
August 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP