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Dose Finding, Safety and Efficacy of Monthly Subcutaneous Canakinumab Administration in Metformin Monotherapy Treated Type 2 Diabetic Patients

Primary Purpose

Diabetes Mellitus, Type 2

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Canakinumab
Metformin
Placebo
Sponsored by
Novartis
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diabetes Mellitus, Type 2 focused on measuring type 2 diabetes, canakinumab

Eligibility Criteria

18 Years - 74 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Patients must have a documented diagnosis of Type 2 diabetes confirmed by World Health Organization (WHO) criteria either a FPG≥ 7.0 mmol/l (126 mg/dl) or an Oral glucose tolerance test (OGTT) test 2-hour PG ≥ 11.1 mmol/l (200 mg/dl).

  2. Patients must:

    • be naïve to anti-diabetes drug therapy (except for short term treatment courses with insulin in connection with hospitalization, etc.)
    • meet protocol specified Glycosylated hemoglobin / hemoglobin A1c (HbA1c) criteria
    • be eligible for metformin monotherapy OR
    • be on stable metformin monotherapy treatment for at least three months at Screening
    • meet protocol specified HbA1c criteria
    • take metformin as their first and only treatment with anti-diabetes drug therapy OR
    • be taking an AGI as their first and only anti-diabetes drug therapy (except short term treatment courses with insulin in connection with hospitalizations, etc)
    • meet protocol specified HbA1c criteria
    • be eligible for metformin monotherapy
  3. Patients must have a morning fasting plasma glucose result < 180 mg/dl at Visit 3 (Month -1) analyzed by the Central Laboratory.
  4. Were on a daily dose of metformin ≥ 1000 mg (or less according to local regulations)

Exclusion Criteria:

  1. Type 1 diabetes, diabetes resulting from pancreatic injury or secondary forms of diabetes.

  2. Any of the following significant laboratory abnormalities:

    • Serum Glutamic acid decarboxylase (GAD)-antibody positivity
    • Clinically significant Thyroid stimulating hormone (TSH) outside of normal range at Screening
    • Renal function indicating high risk metformin use, including serum creatinine concentrations (≥1.5 mg/dL for males, ≥1.4 mg/dL for females) or other evidence of abnormal creatinine clearance.
    • Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) > 2 x upper limit of normal (ULN), or total bilirubin > 2 x ULN and/or direct bilirubin > ULN at Screening, confirmed with repeat measure within one week.
  3. History or current findings of active pulmonary disease as evidenced by a history of positive purified protein derivative (PPD), QuantiFERON-TB Gold (QFT-G), AFB sputum or positive PPD followed by positive chest x-ray or QFT-G, or ongoing antibiotic treatment for latent TB.
  4. Risk factors for TB as defined in protocol
  5. Known presence or suspicion of active or recurrent bacterial, fungal or viral infection at the time of enrollment proven or suspected to be related to immunocompromise including HIV or active or recurrent Hepatitis B and Hepatitis C.
  6. Systemic or local treatment of any immune modulating agent in doses with systemic effects or live vaccinations within 3 months
  7. Stroke, myocardial infarction, acute coronary syndrome, revascularization procedure or recurrent TIA within the last 6 months.
  8. Unwillingness to use insulin glargine as the additional medication should glycemic control deteriorate.

Other protocol-defined inclusion/exclusion criteria may apply

Sites / Locations

  • Anasazi Internal Medicine
  • Whittier Institute of Diabetes
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Orange County Research Center
  • Novartis Investigative Site
  • Deaconess Clinic
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Diabetes Research Center
  • Tri-State Medical Group
  • Preferred Primary Care Physicians
  • Novartis Investigative Site
  • R/D Clinical Research
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Medical Research Initiatives Inc
  • Clinica de Fracturas y Ortopedia
  • DIM Clinica Privada
  • Centro Medico Viamonte
  • Consultorios Asociados de Endocrinologia
  • Hospital Juan Ramon Vidal
  • Novartis Investigative Site
  • Instituto de Investigaciones Biomedicas
  • Centro de Investigaciones Clinicas del Litoral
  • Private Practice - DEMEULEMEESTER
  • Novartis Investigative Site
  • UZ Brussel
  • Novartis Investigative Site
  • Praxis F. Franzmann
  • emovis GmbH
  • Praxis Dr. Stütz
  • GWT-TUB GmbH
  • Gemeinschaftspraxis und Dialysezentrum Karlstraße
  • Asklepios Klinik St. Georg
  • Städt. Kankenhaus Nordstadt
  • Diabeteszentrum Hohenmölsen
  • Johannes Gutenberg-Universität Mainz
  • Zentrum für Klinische Forschung Neuwied (ZKSN)
  • Praxis Dr. Wunderer
  • Praxis Dr. Kosch
  • Praxis Dr. Alawi
  • Praxis Dr. Klein
  • Forschungszentrum Ruhr, KliFoCenter GmbH
  • Fővárosi Önkormányzat Péterfy Sándor Utcai Kórház - Rendelőintézet és Baleseti Központ
  • Sandor Karolyi Hospital
  • Semmelweiss Medical University
  • Kenezy Gyula Korhaz
  • Szegedi Egyetem
  • Zala Megyei Korhaz
  • Gokula Metropolis Clinical Research Centre
  • Bangalore Diabetes Hospital
  • Jnana Sanjeevini Medical Center
  • SAMATVAM
  • Madras Diabetes Reasearch Foundation
  • Amrita Institute of Medical Sciences and Research Center
  • Nizam's Institute of Medical Sciences
  • Diabetes Thyroid Hormone Research Institute Pvt. Ltd.
  • S R Kalla Memorial Gastro & General Hospital
  • Pitale Diabetes & Hormone Centre
  • Health and Research Centre
  • King George Hospital
  • National Hospital Organization Nagoya Medical Center
  • Kyushu Rosai Hospital
  • NHO Yokohama Medical Center
  • Musashikoganei Clinic
  • Novartis Investigative Site
  • Fujikoshi Hospital
  • Saiseikai Fukuoka General Hospital
  • Kokura Medical Center
  • Seino Internal Medicine Clinic
  • Geriatrics Research Institute Hospital
  • Takagi Hospital
  • Sakai Hospital Kinki University School of Medicine
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Instituto Delgado de Investigacion Medica
  • Clinica Chiclayo
  • Hospital Nacional Cayetano Heredia
  • Centro de Investigacion Clinica Trujillo
  • Ambulatory of Institute of Nutrition Diseases and Diabetes
  • Medical Centre "Sanatatea ta"
  • Novartis Investigative Site
  • Policlinica Dr. Citu Timisoara
  • 203 Maxwell Centre
  • Parklands Medical Centre
  • St Augustines Medical Centre
  • Synapta Clinical Research Centre
  • Drs Essack and Mitha
  • PE Greenacres Hospital
  • 26 Daffodil Street
  • Ankara Ataturk Training and Research Hospital
  • Gulhane Askeri Tip Akademisi
  • Hacettepe University Medical Faculty
  • S.B. Yildirim Beyazit Training and Research Hospital
  • Istanbul University Cardiology Institute
  • Ege University Medical Faculty
  • Hayat Tip Merkezi (Hayat Medical Center) Deapartment of Internal Diseases
  • Morriston Hospital
  • Birmingham Heartlands Hospital
  • Royal Bournemouth Hospital
  • Rowden Medical Partnership

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Placebo Comparator

Arm Label

Canakinumab 5 mg + Metformin

Canakinumab 15 mg + Metformin

Canakinumab 50 mg + Metformin

Canakinumab 150 mg + Metformin

Placebo + Metformin

Arm Description

In 4-Month Dose-finding period, patients visited the clinic monthly and had 5 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose >200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy. The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c >7.5% were treated with a daily injection of insulin glargine as add-on therapy.

In 4-Month Dose-finding period, patients visited the clinic monthly and had 15 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose >200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy. The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c >7.5% were treated with a daily injection of insulin glargine as add-on therapy.

In 4-Month Dose-finding period, patients visited the clinic monthly and had 50 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose >200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy. The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c >7.5% were treated with a daily injection of insulin glargine as add-on therapy.

In 4-Month Dose-finding period, patients visited the clinic monthly and had 150 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose >200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy. The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c >7.5% were treated with a daily injection of insulin glargine as add-on therapy.

In 4 month dose finding period as well as during intermediate period, patients received one injection of canakinumab matching placebo monthly and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations).

Outcomes

Primary Outcome Measures

Number of Participants With Adverse Events (AEs), Serious Adverse Events, Death and Clinical Significant AEs During 4 Months (Period II)
Adverse events are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards.
Change From Baseline in Hemoglobin A1c (HbA1c) at Month 4 During Dose-finding Period of the Study (Period II)
HbA1c was measured by National glycohemoglobin standardization program (NGSP) certified methodology. HbA1c is an integrated measure of average glucose concentration in plasma in the last 2-3 months. The analysis of covariance (ANCOVA) included treatment and metformin dose group as main effects and baseline HbA1c as a covariate.
Change From Baseline in Dynamic Phase Secreted Insulin Per Unit of Glucose Concentration (Φd) Over 4 Months (Period III)
This was planned as interim analysis and was not conducted because the study was terminated in period III.

Secondary Outcome Measures

Change From Baseline in C-peptide Area Under Curve (AUC 0-4 Hours ) Following Meal Test (Period II)
A standard liquid mixed-meal challenge was done at baseline and Month 4. Patients completed each standard meal challenge with measurement of C-peptide prior to and after a liquid mixed meal. Sampling times were -20, -10, and -1, 10, 20, 30, 60, 90, 120, 150, 180 and 240 minutes relative to start of meal. C-peptide 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. The analysis of covariance included baseline C-peptide AUC 0-4 hours as a covariate.
Change From Baseline in Prandial Plasma Glucose Area Under Curve (AUC0-4 Hours ) Following Meal Test (Period II)
A standard liquid mixed-meal challenge was done at baseline and Month 4. Patients completed each standard meal challenge with measurement of glucose prior to and after a liquid mixed meal. Sampling times were -20, -10, and -1, 10, 20, 30, 60, 90, 120, 150, 180 and 240 minutes relative to the start of meal. Glucose 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. The model of analysis of covariance included baseline plasma glucose AUC 0-4 hours as a covariate.
Change From Baseline in Insulin Area Under Curve (AUC 0-4 Hours ) Following Meal Test (Period II)
A standard liquid mixed-meal challenge was done at baseline and Month 4. Patients completed each standard meal challenge with measurement of insulin prior to and after a liquid mixed meal. Sampling times were -20, -10, and -1, 10, 20, 30, 60, 90, 120, 150, 180 and 240 minutes relative to the start of meal. 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. Model of analysis of covariance included baseline insulin AUC 0-4 hours as covariate.
Change From Baseline in 2-hour Glucose Level Following Meal Test (Period II)
A standard liquid mixed-meal challenge was done at baseline and Month 4. Patients fasted overnight after 10 pm on day prior to scheduled visit. Study visits should occur before 10 am. Patients completed each standard meal challenge with measurement of glucose prior to and after a liquid mixed meal. The sampling times were -20, -10, and -1, 10, 20, 30, 60, 90, 120, 150, 180 and 240 minutes relative to the start of meal. The analysis of covariance included treatment and metformin dose group as main effects and baseline 2-hour glucose level as covariate.
Change From Baseline in Peak Glucose Level Following Meal Test (Period II)
A standard liquid mixed-meal challenge was done at baseline and Month 4. Patients fasted overnight after 10 pm on day prior to scheduled visit. Study visits should occur before 10 am. Patients completed each standard meal challenge with measurement of glucose prior to and after a liquid mixed meal. The sampling times were -20, -10, and -1, 10, 20, 30, 60, 90, 120, 150, 180 and 240 minutes relative to the start of meal. The analysis of covariance included treatment and metformin dose group as main effects and baseline peak glucose level as covariate.
Change From Baseline in Peak C-peptide Following Meal Test (Period II)
A standard liquid mixed-meal challenge was done at baseline and Month 4. Patients fasted overnight after 10 pm on the day prior to scheduled visit. Study visits should occur before 10 am. Patients completed each standard meal challenge with measurement of C-peptide prior to and after a liquid mixed meal. Sampling times were -20, -10, and -1, 10, 20, 30, 60, 90, 120, 150, 180 and 240 minutes relative to the start of meal. The analysis of covariance included treatment and metformin dose group as main effects and baseline peak C-peptide level as a covariate.
Change From Baseline in Peak Insulin Level Following Meal Test (Period II)
A standard liquid mixed-meal challenge was done at baseline and Month 4. Patients fasted overnight after 10 pm on day prior to scheduled visit. Study visits should occur before 10 am. Patients completed each standard meal challenge with measurement of insulin prior to and after a liquid mixed meal. The sampling times were -20, -10, and -1, 10, 20, 30, 60, 90, 120, 150, 180 and 240 minutes relative to the start of meal. The analysis of covariance included treatment and metformin dose group as main effects and baseline 2-hour insulin level as covariate.
Change From Baseline in Insulin Secretion Rates Relative to Glucose AUC (0-2 Hours) at Month 4 Following Meal Test (Period II)
Change in Insulin Secretion Rate stimulated by Liquid mixed-meal challenge. A standard liquid mixed-meal challenge was done at baseline and Month 4. 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. The model of analysis of covariance included baseline Insulin secretion rate relative to glucose AUC at 0-2 hours as a covariate.
Change From Baseline in 2 Hour Insulin Secretion Rate Derived Based on Glucose and C-peptide Following at Month 4 Following Meal Test (Period II)
A standard liquid mixed-meal challenge was done at baseline and Month 4. A 2 hour insulin secretion rate using deconvolution was performed. The deconvolution was an algorithm that analyzed the insulin secretion rate relative to glucose and C-peptide combined. Blood samples were taken prior to and after meal at sample times: -20, -10, -1 and 10, 20, 30, 60, 90, 120, 180, and 240 minutes relative to the start of the meal. The analysis of covariance included treatment and metformin dose group as main effects and baseline 2 hour Insulin secretion rate as a covariate.
Change From Baseline in Peak Plasma Glucose Level (7-point Glucose Testing) at Month 4(Period II)
Patients were asked to check their glucose level (7 times) using their glucose meter on one of the seven days prior to the Meal Challenge Visits (Period II: baseline, Month 4. Patient was instructed to test at following timepoints: fasting before breakfast, 2 hours after starting breakfast, before lunch, 2 hours after starting lunch, before dinner, 2 hours after dinner and at bedtime. The patient documented the results in their Study Diary. The analysis of covariance included treatment and metformin dose group as main effects and baseline peak plasma glucose level as a covariate.
Change From Baseline in Average Plasma Glucose Level (7-point Glucose Testing) at Month 4 (Period II)
Patients were asked to check their glucose level (7 times) using their glucose meter on one of the seven days prior to the Meal Challenge Visits (Period II: Month 0 (Baseline), Month 4. Patient was instructed to test at following timepoints: fasting before breakfast, 2 hours after starting breakfast, before lunch, 2 hours after starting lunch, before dinner, 2 hours after dinner and at bedtime. Patient documented the results in their Study Diary. The analysis of covariance included treatment and metformin dose group as main effects and baseline average plasma glucose level as a covariate.
Change From Baseline in Fasting Plasma Glucose at Month 4 (Period II)
Change in Fasting Glucose Level measured from plasma taken at Baseline and at Month 4. The analysis of covariance included treatment and metformin dose group as main effects and baseline fasting plasma glucose level as a covariate.
Change From Baseline in Fasting Insulin at Month 4 (Period II)
Change in fasting insulin Level measured from blood samples taken at Baseline and at Month 4. The analysis of covariance included treatment and metformin dose group as main effects and baseline fasting insulin level as a covariate.
Change From Baseline in Homeostatic Model Assessment B (HOMA2 B) Beta Cell Function (%B) at Month 4 (Period II)
The homeostatic model assessment (HOMA) is a method used to quantify insulin resistance and beta (β)-cell function. HOMA2-B is a computer model that uses fasting plasma insulin and glucose concentrations to estimate steady state beta cell function (%B) as a percentage of a normal reference population (normal young adults). Time profile of postprandial glucose, insulin and C-peptide were assessed as measures of β-cell response to stimulation. The analysis of covariance included treatment and metformin dose group as main effects and baseline HOMA-B as a covariate.
Change From Baseline in Homeostatic Model Assessment Insulin Resistance (HOMA2 IR) at Month 4 (Period II)
The homeostatic model assessment (HOMA) is a method used to quantify insulin resistance and beta (β)-cell function. HOMA2-IR is a computer model that uses fasting plasma insulin and glucose concentrations to estimate insulin resistance which is the reciprocal of insulin sensitivity (%S)(100/%S)as a percentage of a normal reference population (normal young adults). The analysis of covariance included treatment and metformin dose group as main effects and baseline HOMA2 IR as a covariate.
Change From Baseline in Quantitative Insulin Sensitivity Check Index (QUICKI) at Month 4 (Period II)
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. The analysis of covariance included treatment and metformin dose group as main effects and baseline QUICKI as a covariate.
Change From Baseline in High-sensitivity C-reactive Protein (hsCRP) at Month 4 (Period II)
The change from baseline in hsCRP (on the logarithmic scale) at Month 4 was measured for this analysis. The analysis of covariance included treatment and metformin dose group as main effects and baseline hsCRP as a covariate.
Percentage Change From Baseline in Fasting Lipids Profile at Month 4 (Period II)
The fasting lipid profiles included triglycerides, total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), calculated very low-density lipoprotein (VLDL), non-HDL cholesterol. Percentage change was measured as [(value at month 4 - baseline value)/baseline value]*100%. The analysis of covariance model included treatment and metformin dose group as main effects and baseline triglycerides, total cholesterol, LDL, HDL, VLDL and non-HDL as covariates.

Full Information

First Posted
May 6, 2009
Last Updated
January 17, 2012
Sponsor
Novartis
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1. Study Identification

Unique Protocol Identification Number
NCT00900146
Brief Title
Dose Finding, Safety and Efficacy of Monthly Subcutaneous Canakinumab Administration in Metformin Monotherapy Treated Type 2 Diabetic Patients
Official Title
Dose Finding, Safety and Efficacy of Monthly Subcutaneous Canakinumab Administration for the Treatment of Hyperglycemia in Metformin Monotherapy Treated Type 2 Diabetic Patients: a Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study
Study Type
Interventional

2. Study Status

Record Verification Date
January 2012
Overall Recruitment Status
Terminated
Why Stopped
Numerically modest lowering of HbA1c with canakinumab in combination with metformin was inadequate to continue patients with T2DM into Period IV of this study.
Study Start Date
April 2009 (undefined)
Primary Completion Date
November 2010 (Actual)
Study Completion Date
November 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis

4. Oversight

5. Study Description

Brief Summary
This was a four month dose ranging study followed by a 24 to 48 month extension at the selected dose to characterize the safety and efficacy of the injectable IL-1B (interleukin 1, beta) antagonist canakinumab in the treatment of patients with Type 2 diabetes mellitus (T2DM) already treated on maximum dose metformin.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, Type 2
Keywords
type 2 diabetes, canakinumab

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
556 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Canakinumab 5 mg + Metformin
Arm Type
Experimental
Arm Description
In 4-Month Dose-finding period, patients visited the clinic monthly and had 5 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose >200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy. The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c >7.5% were treated with a daily injection of insulin glargine as add-on therapy.
Arm Title
Canakinumab 15 mg + Metformin
Arm Type
Experimental
Arm Description
In 4-Month Dose-finding period, patients visited the clinic monthly and had 15 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose >200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy. The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c >7.5% were treated with a daily injection of insulin glargine as add-on therapy.
Arm Title
Canakinumab 50 mg + Metformin
Arm Type
Experimental
Arm Description
In 4-Month Dose-finding period, patients visited the clinic monthly and had 50 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose >200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy. The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c >7.5% were treated with a daily injection of insulin glargine as add-on therapy.
Arm Title
Canakinumab 150 mg + Metformin
Arm Type
Experimental
Arm Description
In 4-Month Dose-finding period, patients visited the clinic monthly and had 150 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose >200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy. The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c >7.5% were treated with a daily injection of insulin glargine as add-on therapy.
Arm Title
Placebo + Metformin
Arm Type
Placebo Comparator
Arm Description
In 4 month dose finding period as well as during intermediate period, patients received one injection of canakinumab matching placebo monthly and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations).
Intervention Type
Drug
Intervention Name(s)
Canakinumab
Intervention Description
Canakinumab lyophilized cake (25 mg and 150 mg in individual 6 mL glass vials ) was reconstituted and then used to dilute the 25mg or 150mg solutions to make 5mg, 15mg and 50mg injections.
Intervention Type
Drug
Intervention Name(s)
Metformin
Intervention Description
Before randomization, in drug naïve patients at a dose of 1000 mg with the evening meal or 500 mg b.i.d. (twice daily) with two main meals. At the randomization visit, patients were prescribed with no less than 1,000mg/day.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo lyophilized cake will be reconstituted and then used to dilute the 25mg or 150mg solutions to make 5mg, 15mg and 50mg injections.
Primary Outcome Measure Information:
Title
Number of Participants With Adverse Events (AEs), Serious Adverse Events, Death and Clinical Significant AEs During 4 Months (Period II)
Description
Adverse events are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards.
Time Frame
4 months (Period II)
Title
Change From Baseline in Hemoglobin A1c (HbA1c) at Month 4 During Dose-finding Period of the Study (Period II)
Description
HbA1c was measured by National glycohemoglobin standardization program (NGSP) certified methodology. HbA1c is an integrated measure of average glucose concentration in plasma in the last 2-3 months. The analysis of covariance (ANCOVA) included treatment and metformin dose group as main effects and baseline HbA1c as a covariate.
Time Frame
Baseline, Month 4
Title
Change From Baseline in Dynamic Phase Secreted Insulin Per Unit of Glucose Concentration (Φd) Over 4 Months (Period III)
Description
This was planned as interim analysis and was not conducted because the study was terminated in period III.
Time Frame
Baseline, Over Month 4
Secondary Outcome Measure Information:
Title
Change From Baseline in C-peptide Area Under Curve (AUC 0-4 Hours ) Following Meal Test (Period II)
Description
A standard liquid mixed-meal challenge was done at baseline and Month 4. Patients completed each standard meal challenge with measurement of C-peptide prior to and after a liquid mixed meal. Sampling times were -20, -10, and -1, 10, 20, 30, 60, 90, 120, 150, 180 and 240 minutes relative to start of meal. C-peptide 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. The analysis of covariance included baseline C-peptide AUC 0-4 hours as a covariate.
Time Frame
Baseline, Month 4
Title
Change From Baseline in Prandial Plasma Glucose Area Under Curve (AUC0-4 Hours ) Following Meal Test (Period II)
Description
A standard liquid mixed-meal challenge was done at baseline and Month 4. Patients completed each standard meal challenge with measurement of glucose prior to and after a liquid mixed meal. Sampling times were -20, -10, and -1, 10, 20, 30, 60, 90, 120, 150, 180 and 240 minutes relative to the start of meal. Glucose 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. The model of analysis of covariance included baseline plasma glucose AUC 0-4 hours as a covariate.
Time Frame
Baseline, Month 4
Title
Change From Baseline in Insulin Area Under Curve (AUC 0-4 Hours ) Following Meal Test (Period II)
Description
A standard liquid mixed-meal challenge was done at baseline and Month 4. Patients completed each standard meal challenge with measurement of insulin prior to and after a liquid mixed meal. Sampling times were -20, -10, and -1, 10, 20, 30, 60, 90, 120, 150, 180 and 240 minutes relative to the start of meal. 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. Model of analysis of covariance included baseline insulin AUC 0-4 hours as covariate.
Time Frame
Baseline, Month 4
Title
Change From Baseline in 2-hour Glucose Level Following Meal Test (Period II)
Description
A standard liquid mixed-meal challenge was done at baseline and Month 4. Patients fasted overnight after 10 pm on day prior to scheduled visit. Study visits should occur before 10 am. Patients completed each standard meal challenge with measurement of glucose prior to and after a liquid mixed meal. The sampling times were -20, -10, and -1, 10, 20, 30, 60, 90, 120, 150, 180 and 240 minutes relative to the start of meal. The analysis of covariance included treatment and metformin dose group as main effects and baseline 2-hour glucose level as covariate.
Time Frame
Baseline, Month 4
Title
Change From Baseline in Peak Glucose Level Following Meal Test (Period II)
Description
A standard liquid mixed-meal challenge was done at baseline and Month 4. Patients fasted overnight after 10 pm on day prior to scheduled visit. Study visits should occur before 10 am. Patients completed each standard meal challenge with measurement of glucose prior to and after a liquid mixed meal. The sampling times were -20, -10, and -1, 10, 20, 30, 60, 90, 120, 150, 180 and 240 minutes relative to the start of meal. The analysis of covariance included treatment and metformin dose group as main effects and baseline peak glucose level as covariate.
Time Frame
Baseline, Month 4
Title
Change From Baseline in Peak C-peptide Following Meal Test (Period II)
Description
A standard liquid mixed-meal challenge was done at baseline and Month 4. Patients fasted overnight after 10 pm on the day prior to scheduled visit. Study visits should occur before 10 am. Patients completed each standard meal challenge with measurement of C-peptide prior to and after a liquid mixed meal. Sampling times were -20, -10, and -1, 10, 20, 30, 60, 90, 120, 150, 180 and 240 minutes relative to the start of meal. The analysis of covariance included treatment and metformin dose group as main effects and baseline peak C-peptide level as a covariate.
Time Frame
Baseline, Month 4
Title
Change From Baseline in Peak Insulin Level Following Meal Test (Period II)
Description
A standard liquid mixed-meal challenge was done at baseline and Month 4. Patients fasted overnight after 10 pm on day prior to scheduled visit. Study visits should occur before 10 am. Patients completed each standard meal challenge with measurement of insulin prior to and after a liquid mixed meal. The sampling times were -20, -10, and -1, 10, 20, 30, 60, 90, 120, 150, 180 and 240 minutes relative to the start of meal. The analysis of covariance included treatment and metformin dose group as main effects and baseline 2-hour insulin level as covariate.
Time Frame
Baseline, Month 4
Title
Change From Baseline in Insulin Secretion Rates Relative to Glucose AUC (0-2 Hours) at Month 4 Following Meal Test (Period II)
Description
Change in Insulin Secretion Rate stimulated by Liquid mixed-meal challenge. A standard liquid mixed-meal challenge was done at baseline and Month 4. 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. The model of analysis of covariance included baseline Insulin secretion rate relative to glucose AUC at 0-2 hours as a covariate.
Time Frame
Baseline, Month 4
Title
Change From Baseline in 2 Hour Insulin Secretion Rate Derived Based on Glucose and C-peptide Following at Month 4 Following Meal Test (Period II)
Description
A standard liquid mixed-meal challenge was done at baseline and Month 4. A 2 hour insulin secretion rate using deconvolution was performed. The deconvolution was an algorithm that analyzed the insulin secretion rate relative to glucose and C-peptide combined. Blood samples were taken prior to and after meal at sample times: -20, -10, -1 and 10, 20, 30, 60, 90, 120, 180, and 240 minutes relative to the start of the meal. The analysis of covariance included treatment and metformin dose group as main effects and baseline 2 hour Insulin secretion rate as a covariate.
Time Frame
Baseline, Month 4
Title
Change From Baseline in Peak Plasma Glucose Level (7-point Glucose Testing) at Month 4(Period II)
Description
Patients were asked to check their glucose level (7 times) using their glucose meter on one of the seven days prior to the Meal Challenge Visits (Period II: baseline, Month 4. Patient was instructed to test at following timepoints: fasting before breakfast, 2 hours after starting breakfast, before lunch, 2 hours after starting lunch, before dinner, 2 hours after dinner and at bedtime. The patient documented the results in their Study Diary. The analysis of covariance included treatment and metformin dose group as main effects and baseline peak plasma glucose level as a covariate.
Time Frame
Baseline, Month 4
Title
Change From Baseline in Average Plasma Glucose Level (7-point Glucose Testing) at Month 4 (Period II)
Description
Patients were asked to check their glucose level (7 times) using their glucose meter on one of the seven days prior to the Meal Challenge Visits (Period II: Month 0 (Baseline), Month 4. Patient was instructed to test at following timepoints: fasting before breakfast, 2 hours after starting breakfast, before lunch, 2 hours after starting lunch, before dinner, 2 hours after dinner and at bedtime. Patient documented the results in their Study Diary. The analysis of covariance included treatment and metformin dose group as main effects and baseline average plasma glucose level as a covariate.
Time Frame
Baseline, Month 4
Title
Change From Baseline in Fasting Plasma Glucose at Month 4 (Period II)
Description
Change in Fasting Glucose Level measured from plasma taken at Baseline and at Month 4. The analysis of covariance included treatment and metformin dose group as main effects and baseline fasting plasma glucose level as a covariate.
Time Frame
Baseline, Month 4
Title
Change From Baseline in Fasting Insulin at Month 4 (Period II)
Description
Change in fasting insulin Level measured from blood samples taken at Baseline and at Month 4. The analysis of covariance included treatment and metformin dose group as main effects and baseline fasting insulin level as a covariate.
Time Frame
Baseline, Month 4
Title
Change From Baseline in Homeostatic Model Assessment B (HOMA2 B) Beta Cell Function (%B) at Month 4 (Period II)
Description
The homeostatic model assessment (HOMA) is a method used to quantify insulin resistance and beta (β)-cell function. HOMA2-B is a computer model that uses fasting plasma insulin and glucose concentrations to estimate steady state beta cell function (%B) as a percentage of a normal reference population (normal young adults). Time profile of postprandial glucose, insulin and C-peptide were assessed as measures of β-cell response to stimulation. The analysis of covariance included treatment and metformin dose group as main effects and baseline HOMA-B as a covariate.
Time Frame
Baseline, Month 4
Title
Change From Baseline in Homeostatic Model Assessment Insulin Resistance (HOMA2 IR) at Month 4 (Period II)
Description
The homeostatic model assessment (HOMA) is a method used to quantify insulin resistance and beta (β)-cell function. HOMA2-IR is a computer model that uses fasting plasma insulin and glucose concentrations to estimate insulin resistance which is the reciprocal of insulin sensitivity (%S)(100/%S)as a percentage of a normal reference population (normal young adults). The analysis of covariance included treatment and metformin dose group as main effects and baseline HOMA2 IR as a covariate.
Time Frame
Baseline, Month 4
Title
Change From Baseline in Quantitative Insulin Sensitivity Check Index (QUICKI) at Month 4 (Period II)
Description
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. The analysis of covariance included treatment and metformin dose group as main effects and baseline QUICKI as a covariate.
Time Frame
Baseline, Month 4
Title
Change From Baseline in High-sensitivity C-reactive Protein (hsCRP) at Month 4 (Period II)
Description
The change from baseline in hsCRP (on the logarithmic scale) at Month 4 was measured for this analysis. The analysis of covariance included treatment and metformin dose group as main effects and baseline hsCRP as a covariate.
Time Frame
Baseline, Month 4
Title
Percentage Change From Baseline in Fasting Lipids Profile at Month 4 (Period II)
Description
The fasting lipid profiles included triglycerides, total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), calculated very low-density lipoprotein (VLDL), non-HDL cholesterol. Percentage change was measured as [(value at month 4 - baseline value)/baseline value]*100%. The analysis of covariance model included treatment and metformin dose group as main effects and baseline triglycerides, total cholesterol, LDL, HDL, VLDL and non-HDL as covariates.
Time Frame
Baseline, Month 4

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
74 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients must have a documented diagnosis of Type 2 diabetes confirmed by World Health Organization (WHO) criteria either a FPG≥ 7.0 mmol/l (126 mg/dl) or an Oral glucose tolerance test (OGTT) test 2-hour PG ≥ 11.1 mmol/l (200 mg/dl). Patients must: be naïve to anti-diabetes drug therapy (except for short term treatment courses with insulin in connection with hospitalization, etc.) meet protocol specified Glycosylated hemoglobin / hemoglobin A1c (HbA1c) criteria be eligible for metformin monotherapy OR be on stable metformin monotherapy treatment for at least three months at Screening meet protocol specified HbA1c criteria take metformin as their first and only treatment with anti-diabetes drug therapy OR be taking an AGI as their first and only anti-diabetes drug therapy (except short term treatment courses with insulin in connection with hospitalizations, etc) meet protocol specified HbA1c criteria be eligible for metformin monotherapy Patients must have a morning fasting plasma glucose result < 180 mg/dl at Visit 3 (Month -1) analyzed by the Central Laboratory. Were on a daily dose of metformin ≥ 1000 mg (or less according to local regulations) Exclusion Criteria: Type 1 diabetes, diabetes resulting from pancreatic injury or secondary forms of diabetes. Any of the following significant laboratory abnormalities: Serum Glutamic acid decarboxylase (GAD)-antibody positivity Clinically significant Thyroid stimulating hormone (TSH) outside of normal range at Screening Renal function indicating high risk metformin use, including serum creatinine concentrations (≥1.5 mg/dL for males, ≥1.4 mg/dL for females) or other evidence of abnormal creatinine clearance. Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) > 2 x upper limit of normal (ULN), or total bilirubin > 2 x ULN and/or direct bilirubin > ULN at Screening, confirmed with repeat measure within one week. History or current findings of active pulmonary disease as evidenced by a history of positive purified protein derivative (PPD), QuantiFERON-TB Gold (QFT-G), AFB sputum or positive PPD followed by positive chest x-ray or QFT-G, or ongoing antibiotic treatment for latent TB. Risk factors for TB as defined in protocol Known presence or suspicion of active or recurrent bacterial, fungal or viral infection at the time of enrollment proven or suspected to be related to immunocompromise including HIV or active or recurrent Hepatitis B and Hepatitis C. Systemic or local treatment of any immune modulating agent in doses with systemic effects or live vaccinations within 3 months Stroke, myocardial infarction, acute coronary syndrome, revascularization procedure or recurrent TIA within the last 6 months. Unwillingness to use insulin glargine as the additional medication should glycemic control deteriorate. Other protocol-defined inclusion/exclusion criteria may apply
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals Corporation
Organizational Affiliation
Sponsor GmbH
Official's Role
Study Director
Facility Information:
Facility Name
Anasazi Internal Medicine
City
Phoenix
State/Province
Arizona
Country
United States
Facility Name
Whittier Institute of Diabetes
City
La Jolla
State/Province
California
Country
United States
Facility Name
Novartis Investigative Site
City
Los Gatos
State/Province
California
Country
United States
Facility Name
Novartis Investigative Site
City
Santa Monica
State/Province
California
ZIP/Postal Code
90404
Country
United States
Facility Name
Orange County Research Center
City
Tustin
State/Province
California
Country
United States
Facility Name
Novartis Investigative Site
City
Atlanta
State/Province
Georgia
Country
United States
Facility Name
Deaconess Clinic
City
Evansville
State/Province
Indiana
Country
United States
Facility Name
Novartis Investigative Site
City
Jackson
State/Province
Mississippi
Country
United States
Facility Name
Novartis Investigative Site
City
Picayune
State/Province
Mississippi
Country
United States
Facility Name
Novartis Investigative Site
City
Trenton
State/Province
New Jersey
Country
United States
Facility Name
Diabetes Research Center
City
Columbus
State/Province
Ohio
Country
United States
Facility Name
Tri-State Medical Group
City
Beaver
State/Province
Pennsylvania
Country
United States
Facility Name
Preferred Primary Care Physicians
City
Pittsburgh
State/Province
Pennsylvania
Country
United States
Facility Name
Novartis Investigative Site
City
Columbia
State/Province
South Carolina
Country
United States
Facility Name
R/D Clinical Research
City
Lake Jackson
State/Province
Texas
Country
United States
Facility Name
Novartis Investigative Site
City
Pasadena
State/Province
Texas
Country
United States
Facility Name
Novartis Investigative Site
City
San Antonio
State/Province
Texas
Country
United States
Facility Name
Medical Research Initiatives Inc
City
Virginia Beach
State/Province
Virginia
Country
United States
Facility Name
Clinica de Fracturas y Ortopedia
City
Mar del Plata
State/Province
Buenos Aires
ZIP/Postal Code
C1100ABB
Country
Argentina
Facility Name
DIM Clinica Privada
City
Buenos Aires
ZIP/Postal Code
B1704ETD
Country
Argentina
Facility Name
Centro Medico Viamonte
City
Buenos Aires
ZIP/Postal Code
C1120AAC
Country
Argentina
Facility Name
Consultorios Asociados de Endocrinologia
City
Buenos Aires
ZIP/Postal Code
C1425AGC
Country
Argentina
Facility Name
Hospital Juan Ramon Vidal
City
Corrientes
ZIP/Postal Code
W3410AVV
Country
Argentina
Facility Name
Novartis Investigative Site
City
Rosario Santa Fe
ZIP/Postal Code
S2000AII
Country
Argentina
Facility Name
Instituto de Investigaciones Biomedicas
City
Santa Fe
ZIP/Postal Code
S3000FNF
Country
Argentina
Facility Name
Centro de Investigaciones Clinicas del Litoral
City
Santa Fe
ZIP/Postal Code
S3000FWO
Country
Argentina
Facility Name
Private Practice - DEMEULEMEESTER
City
Gozée
Country
Belgium
Facility Name
Novartis Investigative Site
City
Heist-op-den-berg
Country
Belgium
Facility Name
UZ Brussel
City
Jette
Country
Belgium
Facility Name
Novartis Investigative Site
City
Hong Kong
Country
China
Facility Name
Praxis F. Franzmann
City
Bad Oeynhausen
ZIP/Postal Code
32549
Country
Germany
Facility Name
emovis GmbH
City
Berlin
ZIP/Postal Code
10629
Country
Germany
Facility Name
Praxis Dr. Stütz
City
Bretten
ZIP/Postal Code
75015
Country
Germany
Facility Name
GWT-TUB GmbH
City
Dresden
ZIP/Postal Code
01307
Country
Germany
Facility Name
Gemeinschaftspraxis und Dialysezentrum Karlstraße
City
Düsseldorf
Country
Germany
Facility Name
Asklepios Klinik St. Georg
City
Hamburg
ZIP/Postal Code
20099
Country
Germany
Facility Name
Städt. Kankenhaus Nordstadt
City
Hannover
ZIP/Postal Code
30167
Country
Germany
Facility Name
Diabeteszentrum Hohenmölsen
City
Hohenmölsen
ZIP/Postal Code
06679
Country
Germany
Facility Name
Johannes Gutenberg-Universität Mainz
City
Mainz
ZIP/Postal Code
55101
Country
Germany
Facility Name
Zentrum für Klinische Forschung Neuwied (ZKSN)
City
Neuwied
ZIP/Postal Code
56564
Country
Germany
Facility Name
Praxis Dr. Wunderer
City
Nürnberg
ZIP/Postal Code
90489
Country
Germany
Facility Name
Praxis Dr. Kosch
City
Pirna
ZIP/Postal Code
01796
Country
Germany
Facility Name
Praxis Dr. Alawi
City
Saarlouis
ZIP/Postal Code
66740
Country
Germany
Facility Name
Praxis Dr. Klein
City
Schenklengsfeld
ZIP/Postal Code
36277
Country
Germany
Facility Name
Forschungszentrum Ruhr, KliFoCenter GmbH
City
Witten
ZIP/Postal Code
58455
Country
Germany
Facility Name
Fővárosi Önkormányzat Péterfy Sándor Utcai Kórház - Rendelőintézet és Baleseti Központ
City
Budapest
Country
Hungary
Facility Name
Sandor Karolyi Hospital
City
Budapest
Country
Hungary
Facility Name
Semmelweiss Medical University
City
Budapest
Country
Hungary
Facility Name
Kenezy Gyula Korhaz
City
Debrecen
Country
Hungary
Facility Name
Szegedi Egyetem
City
Szeged
Country
Hungary
Facility Name
Zala Megyei Korhaz
City
Zalaegerszeg
Country
Hungary
Facility Name
Gokula Metropolis Clinical Research Centre
City
Bangalore-
Country
India
Facility Name
Bangalore Diabetes Hospital
City
Bangalore
Country
India
Facility Name
Jnana Sanjeevini Medical Center
City
Bangalore
Country
India
Facility Name
SAMATVAM
City
Bangalore
Country
India
Facility Name
Madras Diabetes Reasearch Foundation
City
Chennai
Country
India
Facility Name
Amrita Institute of Medical Sciences and Research Center
City
Cochin
Country
India
Facility Name
Nizam's Institute of Medical Sciences
City
Hyderabaad
Country
India
Facility Name
Diabetes Thyroid Hormone Research Institute Pvt. Ltd.
City
Indore
Country
India
Facility Name
S R Kalla Memorial Gastro & General Hospital
City
Jaipur
Country
India
Facility Name
Pitale Diabetes & Hormone Centre
City
Nagpur
Country
India
Facility Name
Health and Research Centre
City
Trivandrum
Country
India
Facility Name
King George Hospital
City
Visakhapatnam
Country
India
Facility Name
National Hospital Organization Nagoya Medical Center
City
Nagoya
State/Province
Aichi
ZIP/Postal Code
460-0001
Country
Japan
Facility Name
Kyushu Rosai Hospital
City
Kitakyushu
State/Province
Fukuoka
ZIP/Postal Code
800-0296
Country
Japan
Facility Name
NHO Yokohama Medical Center
City
Yokohama
State/Province
Kanagawa
ZIP/Postal Code
245-8575
Country
Japan
Facility Name
Musashikoganei Clinic
City
Koganei-city
State/Province
Tokyo
ZIP/Postal Code
184-0004
Country
Japan
Facility Name
Novartis Investigative Site
City
Minato-ku
State/Province
Tokyo
Country
Japan
Facility Name
Fujikoshi Hospital
City
Toyama-city
State/Province
Toyama
ZIP/Postal Code
930-0964
Country
Japan
Facility Name
Saiseikai Fukuoka General Hospital
City
Fukuoka
ZIP/Postal Code
810-0001
Country
Japan
Facility Name
Kokura Medical Center
City
Kitakyusyu
Country
Japan
Facility Name
Seino Internal Medicine Clinic
City
Koriyama
Country
Japan
Facility Name
Geriatrics Research Institute Hospital
City
Maebashi
Country
Japan
Facility Name
Takagi Hospital
City
Ohkawa
Country
Japan
Facility Name
Sakai Hospital Kinki University School of Medicine
City
Sakai
Country
Japan
Facility Name
Novartis Investigative Site
City
Pusan
ZIP/Postal Code
614-735
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Seoul
ZIP/Postal Code
135-710
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Seoul
ZIP/Postal Code
135-720
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Seoul
ZIP/Postal Code
139-872
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Suwon
ZIP/Postal Code
442-721
Country
Korea, Republic of
Facility Name
Instituto Delgado de Investigacion Medica
City
Arequipa
Country
Peru
Facility Name
Clinica Chiclayo
City
Chiclayo
Country
Peru
Facility Name
Hospital Nacional Cayetano Heredia
City
San Martin de Porres
Country
Peru
Facility Name
Centro de Investigacion Clinica Trujillo
City
Trujillo
Country
Peru
Facility Name
Ambulatory of Institute of Nutrition Diseases and Diabetes
City
Bucharest
Country
Romania
Facility Name
Medical Centre "Sanatatea ta"
City
Bucuresti
Country
Romania
Facility Name
Novartis Investigative Site
City
Bucuresti
Country
Romania
Facility Name
Policlinica Dr. Citu Timisoara
City
Timisoara
Country
Romania
Facility Name
203 Maxwell Centre
City
Durban
Country
South Africa
Facility Name
Parklands Medical Centre
City
Durban
Country
South Africa
Facility Name
St Augustines Medical Centre
City
Durban
Country
South Africa
Facility Name
Synapta Clinical Research Centre
City
Durban
Country
South Africa
Facility Name
Drs Essack and Mitha
City
Johannesburg
Country
South Africa
Facility Name
PE Greenacres Hospital
City
Port Elizabeth
Country
South Africa
Facility Name
26 Daffodil Street
City
Stanger
Country
South Africa
Facility Name
Ankara Ataturk Training and Research Hospital
City
Ankara
Country
Turkey
Facility Name
Gulhane Askeri Tip Akademisi
City
Ankara
Country
Turkey
Facility Name
Hacettepe University Medical Faculty
City
Ankara
Country
Turkey
Facility Name
S.B. Yildirim Beyazit Training and Research Hospital
City
Ankara
Country
Turkey
Facility Name
Istanbul University Cardiology Institute
City
Istanbul
Country
Turkey
Facility Name
Ege University Medical Faculty
City
Izmir
Country
Turkey
Facility Name
Hayat Tip Merkezi (Hayat Medical Center) Deapartment of Internal Diseases
City
Karabuk
Country
Turkey
Facility Name
Morriston Hospital
City
Swansea
State/Province
England
ZIP/Postal Code
SA6 6NL
Country
United Kingdom
Facility Name
Birmingham Heartlands Hospital
City
Birmingham
Country
United Kingdom
Facility Name
Royal Bournemouth Hospital
City
Bournemouth
Country
United Kingdom
Facility Name
Rowden Medical Partnership
City
Wiltshire
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
25240532
Citation
Noe A, Howard C, Thuren T, Taylor A, Skerjanec A. Pharmacokinetic and pharmacodynamic characteristics of single-dose Canakinumab in patients with type 2 diabetes mellitus. Clin Ther. 2014 Nov 1;36(11):1625-37. doi: 10.1016/j.clinthera.2014.08.004. Epub 2014 Sep 18.
Results Reference
derived
PubMed Identifier
24075453
Citation
Hensen J, Howard CP, Walter V, Thuren T. Impact of interleukin-1beta antibody (canakinumab) on glycaemic indicators in patients with type 2 diabetes mellitus: results of secondary endpoints from a randomized, placebo-controlled trial. Diabetes Metab. 2013 Dec;39(6):524-31. doi: 10.1016/j.diabet.2013.07.003. Epub 2013 Sep 25.
Results Reference
derived
PubMed Identifier
23129601
Citation
Ridker PM, Howard CP, Walter V, Everett B, Libby P, Hensen J, Thuren T; CANTOS Pilot Investigative Group. Effects of interleukin-1beta inhibition with canakinumab on hemoglobin A1c, lipids, C-reactive protein, interleukin-6, and fibrinogen: a phase IIb randomized, placebo-controlled trial. Circulation. 2012 Dec 4;126(23):2739-48. doi: 10.1161/CIRCULATIONAHA.112.122556. Epub 2012 Nov 5.
Results Reference
derived

Learn more about this trial

Dose Finding, Safety and Efficacy of Monthly Subcutaneous Canakinumab Administration in Metformin Monotherapy Treated Type 2 Diabetic Patients

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