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

Novartis246 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

246

Conditions

Type 2 Diabetes Mellitus Impaired Glucose Tolerance

Interventions

Canakinumab 150 mgDRUG

Single subcutaneous injection of Canakinumab 150 mg.

Placebo to CanakinumabDRUG

Single subcutaneous injection of Placebo to Canakinumab.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 74 Years

Medical Language ↔ Plain English

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.

Locations (52)

Outcomes

Primary Outcomes

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

Time frame: Baseline, 4 weeks

Secondary Outcomes

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

Time frame: Baseline, 4 weeks

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.

Time frame: Baseline, 4 weeks

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

National Research Institute

Los Angeles, California, United States

Crest Clinical Trials

Santa Ana, California, United States

Encompass Clinical Research

Spring Valley, 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

Lillestol Research LLC

Fargo, North Dakota, United States

Preferred Primary Care Physicians

Pittsburgh, Pennsylvania, United States

Dallas Diabetes and Endocrine Center

Dallas, Texas, United States

Texas Center for Drug Development P.A.

Houston, Texas, United States

...and 42 more locations

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

Time frame: Baseline, 4 weeks

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

Time frame: Baseline, 4 weeks

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

Time frame: Baseline, 4 weeks

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.

Time frame: Baseline, 4 weeks

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 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.

Time frame: Baseline, 4 weeks

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.

Time frame: Baseline, 4 weeks

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 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.

Time frame: Baseline, 4 weeks

Mean Change in C-peptide Area Under the Curve (AUC), 0-4 Hours, From Baseline to 4 Weeks

Time frame: Baseline, 4 weeks

Mean Change in Post-prandial Glucose Area Under the Curve (AUC)0-4 Hours, From Baseline to 4 Weeks

Time frame: Baseline, 4 weeks

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.

Time frame: Baseline, 4 weeks

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.

Time frame: Baseline, 4 weeks

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.

Time frame: Baseline, 4 weeks

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.

Time frame: Baseline, 4 weeks