Not provided
Not provided
Not provided
Not provided
Not provided
Numerically modest lowering of HbA1c with canakinumab in combination with metformin was inadequate to continue patients with T2DM into Period IV of this study.
Not provided
Not provided
Not provided
Not provided
Not provided
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Canakinumab 5 mg + Metformin | Experimental | 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. |
|
| Canakinumab 15 mg + Metformin | Experimental | 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. |
|
| Canakinumab 50 mg + Metformin | Experimental | 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Canakinumab | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 4 months (Period II) |
| 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. | Baseline, Month 4 |
| 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. | Baseline, Over Month 4 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
Not provided
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:
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:
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
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals Corporation | Sponsor GmbH | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Anasazi Internal Medicine | Phoenix | Arizona | United States | |||
| Whittier Institute of Diabetes |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25240532 | Derived | 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. | |
| 24075453 | Derived | 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. |
Not provided
Not provided
A total of 556 patients were randomized in Period II. 5 patients one in each 5, 15, 50mg Canakinumab arms and 2 in Placebo were randomized in error, but never received study treatment. All tables reflect the 551 treated patients.
Study consisted of four periods: screening (Period I), dose-finding (Period II), intermediate (Period III),and long-term continuation (Period IV). Eligible patients were randomized for 4-month treatment of Period II. Intermediate period continued until primary analysis was completed and optimal dose was selected. Study got terminated in Period III.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Canakinumab 5 mg + Metformin | 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. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Dose Finding: Period II (4 Months) |
|
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| Canakinumab 150 mg + Metformin | Experimental | 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. |
|
| Placebo + Metformin | Placebo Comparator | 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). |
|
| Metformin | Drug | 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. |
|
| Placebo | Drug | Placebo lyophilized cake will be reconstituted and then used to dilute the 25mg or 150mg solutions to make 5mg, 15mg and 50mg injections. |
|
| Baseline, Month 4 |
| 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. | Baseline, Month 4 |
| 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. | Baseline, Month 4 |
| 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. | Baseline, Month 4 |
| 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. | Baseline, Month 4 |
| 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. | Baseline, Month 4 |
| 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. | Baseline, Month 4 |
| 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. | Baseline, Month 4 |
| 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. | Baseline, Month 4 |
| 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. | Baseline, Month 4 |
| 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. | Baseline, Month 4 |
| 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. | Baseline, Month 4 |
| 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. | Baseline, Month 4 |
| 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. | Baseline, Month 4 |
| 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. | Baseline, Month 4 |
| 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. | Baseline, Month 4 |
| 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. | Baseline, Month 4 |
| 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. | Baseline, Month 4 |
| La Jolla |
| California |
| United States |
| Novartis Investigative Site | Los Gatos | California | United States |
| Novartis Investigative Site | Santa Monica | California | 90404 | United States |
| Orange County Research Center | Tustin | California | United States |
| Novartis Investigative Site | Atlanta | Georgia | United States |
| Deaconess Clinic | Evansville | Indiana | United States |
| Novartis Investigative Site | Jackson | Mississippi | United States |
| Novartis Investigative Site | Picayune | Mississippi | United States |
| Novartis Investigative Site | Trenton | New Jersey | United States |
| Diabetes Research Center | Columbus | Ohio | United States |
| Tri-State Medical Group | Beaver | Pennsylvania | United States |
| Preferred Primary Care Physicians | Pittsburgh | Pennsylvania | United States |
| Novartis Investigative Site | Columbia | South Carolina | United States |
| R/D Clinical Research | Lake Jackson | Texas | United States |
| Novartis Investigative Site | Pasadena | Texas | United States |
| Novartis Investigative Site | San Antonio | Texas | United States |
| Medical Research Initiatives Inc | Virginia Beach | Virginia | United States |
| DIM Clinica Privada | Buenos Aires | Buenos Aires | B1704ETD | Argentina |
| Centro Medico Viamonte | Buenos Aires | Buenos Aires | C1120AAC | Argentina |
| Consultorios Asociados de Endocrinologia | Buenos Aires | Buenos Aires | C1425AGC | Argentina |
| Clinica de Fracturas y Ortopedia | Mar del Plata | Buenos Aires | C1100ABB | Argentina |
| Hospital Juan Ramon Vidal | Corrientes | Corrientes Province | W3410AVV | Argentina |
| Instituto de Investigaciones Biomedicas | Santa Fe | Santa Fe Province | S3000FNF | Argentina |
| Centro de Investigaciones Clinicas del Litoral | Santa Fe | Santa Fe Province | S3000FWO | Argentina |
| Novartis Investigative Site | Rosario Santa Fe | S2000AII | Argentina |
| Private Practice - DEMEULEMEESTER | Gozée | Belgium |
| Novartis Investigative Site | Heist-op-den-Berg | Belgium |
| UZ Brussel | Jette | Belgium |
| Novartis Investigative Site | Hong Kong | China |
| Praxis F. Franzmann | Bad Oeynhausen | 32549 | Germany |
| emovis GmbH | Berlin | 10629 | Germany |
| Praxis Dr. Stütz | Bretten | 75015 | Germany |
| GWT-TUB GmbH | Dresden | 01307 | Germany |
| Gemeinschaftspraxis und Dialysezentrum Karlstraße | Düsseldorf | Germany |
| Asklepios Klinik St. Georg | Hamburg | 20099 | Germany |
| Städt. Kankenhaus Nordstadt | Hanover | 30167 | Germany |
| Diabeteszentrum Hohenmölsen | Hohenmölsen | 06679 | Germany |
| Johannes Gutenberg-Universität Mainz | Mainz | 55101 | Germany |
| Zentrum für Klinische Forschung Neuwied (ZKSN) | Neuwied | 56564 | Germany |
| Praxis Dr. Wunderer | Nuremberg | 90489 | Germany |
| Praxis Dr. Kosch | Pirna | 01796 | Germany |
| Praxis Dr. Alawi | Saarlouis | 66740 | Germany |
| Praxis Dr. Klein | Schenklengsfeld | 36277 | Germany |
| Forschungszentrum Ruhr, KliFoCenter GmbH | Witten | 58455 | Germany |
| Fővárosi Önkormányzat Péterfy Sándor Utcai Kórház - Rendelőintézet és Baleseti Központ | Budapest | Hungary |
| Sandor Karolyi Hospital | Budapest | Hungary |
| Semmelweiss Medical University | Budapest | Hungary |
| Kenezy Gyula Korhaz | Debrecen | Hungary |
| Szegedi Egyetem | Szeged | Hungary |
| Zala Megyei Korhaz | Zalaegerszeg | Hungary |
| Bangalore Diabetes Hospital | Bangalore | India |
| Gokula Metropolis Clinical Research Centre | Bangalore | India |
| Jnana Sanjeevini Medical Center | Bangalore | India |
| SAMATVAM | Bangalore | India |
| Madras Diabetes Reasearch Foundation | Chennai | India |
| Nizam's Institute of Medical Sciences | Hyderabaad | India |
| Diabetes Thyroid Hormone Research Institute Pvt. Ltd. | Indore | India |
| S R Kalla Memorial Gastro & General Hospital | Jaipur | India |
| Amrita Institute of Medical Sciences and Research Center | Kochi | India |
| Pitale Diabetes & Hormone Centre | Nagpur | India |
| Health and Research Centre | Trivandrum | India |
| King George Hospital | Visakhapatnam | India |
| National Hospital Organization Nagoya Medical Center | Nagoya | Aichi-ken | 460-0001 | Japan |
| Saiseikai Fukuoka General Hospital | Fukuoka | Fukuoka | 810-0001 | Japan |
| Kyushu Rosai Hospital | Kitakyushu | Fukuoka | 800-0296 | Japan |
| NHO Yokohama Medical Center | Yokohama | Kanagawa | 245-8575 | Japan |
| Musashikoganei Clinic | Koganei | Tokyo | 184-0004 | Japan |
| Novartis Investigative Site | Minato-ku | Tokyo | Japan |
| Fujikoshi Hospital | Toyama | Toyama | 930-0964 | Japan |
| Kokura Medical Center | Kitakyushu | Japan |
| Seino Internal Medicine Clinic | Kōriyama | Japan |
| Geriatrics Research Institute Hospital | Maebashi | Japan |
| Takagi Hospital | Ohkawa | Japan |
| Sakai Hospital Kinki University School of Medicine | Sakai | Japan |
| Instituto Delgado de Investigacion Medica | Arequipa | Peru |
| Clinica Chiclayo | Chiclayo | Peru |
| Hospital Nacional Cayetano Heredia | San Martín de Porres | Peru |
| Centro de Investigacion Clinica Trujillo | Trujillo | Peru |
| Ambulatory of Institute of Nutrition Diseases and Diabetes | Bucharest | Romania |
| Medical Centre "Sanatatea ta" | Bucharest | Romania |
| Novartis Investigative Site | Bucharest | Romania |
| Policlinica Dr. Citu Timisoara | Timișoara | Romania |
| 203 Maxwell Centre | Durban | South Africa |
| Parklands Medical Centre | Durban | South Africa |
| St Augustines Medical Centre | Durban | South Africa |
| Synapta Clinical Research Centre | Durban | South Africa |
| Drs Essack and Mitha | Johannesburg | South Africa |
| 26 Daffodil Street | KwaDukuza | South Africa |
| PE Greenacres Hospital | Port Elizabeth | South Africa |
| Novartis Investigative Site | Pusan | 614-735 | South Korea |
| Novartis Investigative Site | Seoul | 135-710 | South Korea |
| Novartis Investigative Site | Seoul | 135-720 | South Korea |
| Novartis Investigative Site | Seoul | 139-872 | South Korea |
| Novartis Investigative Site | Suwon | 442-721 | South Korea |
| Ankara Ataturk Training and Research Hospital | Ankara | Turkey (Türkiye) |
| Gulhane Askeri Tip Akademisi | Ankara | Turkey (Türkiye) |
| Hacettepe University Medical Faculty | Ankara | Turkey (Türkiye) |
| S.B. Yildirim Beyazit Training and Research Hospital | Ankara | Turkey (Türkiye) |
| Istanbul University Cardiology Institute | Istanbul | Turkey (Türkiye) |
| Ege University Medical Faculty | Izmir | Turkey (Türkiye) |
| Hayat Tip Merkezi (Hayat Medical Center) Deapartment of Internal Diseases | Karabük | Turkey (Türkiye) |
| Morriston Hospital | Swansea | England | SA6 6NL | United Kingdom |
| Birmingham Heartlands Hospital | Birmingham | United Kingdom |
| Royal Bournemouth Hospital | Bournemouth | United Kingdom |
| Rowden Medical Partnership | Wiltshire | United Kingdom |
| 23129601 | Derived | 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. |
| FG001 | Canakinumab 15 mg + Metformin | 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. |
| FG002 | Canakinumab 50 mg + Metformin | 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. |
| FG003 | Canakinumab 150 mg + Metformin | 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. |
| FG004 | Placebo + Metformin | 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). |
| Full Analysis Set (FAS)/Safety |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
| Intermediate: Period III |
|
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Canakinumab 5 mg + Metformin | 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. |
| BG001 | Canakinumab 15 mg + Metformin | 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. |
| BG002 | Canakinumab 50 mg + Metformin | 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. |
| BG003 | Canakinumab 150 mg + Metformin | 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. |
| BG004 | Placebo + Metformin | 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). |
| BG005 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age Continuous | Baseline measures were based on the full analysis set (FAS) which included all randomized patients except for mis-randomized patients. Mis-randomized patients referred to patients who are not qualified for randomization but who were inadvertently randomized into the study and did not receive study drug. | Mean | Standard Deviation | years |
| ||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | The safety set (SAF) included all patients who received at least one dose of study medication during Period II. | Posted | Number | Participants | 4 months (Period II) |
|
|
| ||||||||||||||||||||||||||||||||||||||
| Primary | 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. | The full analysis set (included all randomized patients except for mis-randomized patients who randomized in error but did not receive study drug. Last observation carried forward (LOCF) method was used for patients without Month 4 HbA1c data for any reason and who used rescue medication or any other glucose lowering agents other than metformin. | Posted | Least Squares Mean | Standard Error | percentage of hemoglobin A1c | Baseline, Month 4 |
| |||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | The full analysis set included all randomized patients except for mis-randomized patients who inadvertently randomized into study and did not receive study drug. Last observation carried forward method was used for patients without Month 4 data for any reason and who used rescue medication or any other glucose lowering agents other than metformin. | Posted | Least Squares Mean | Standard Error | nmol*hour/L | Baseline, Month 4 |
| |||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | The full analysis set included all randomized patients except for mis-randomized patients who inadvertently randomized into study and did not receive study drug. Last observation carried forward method was used for patients without Month 4 data for any reason and who used rescue medication or any other glucose lowering agents other than metformin. | Posted | Least Squares Mean | Standard Error | mmol*hour/L | Baseline, Month 4 |
| |||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | The full analysis set included all randomized patients except for mis-randomized patients who inadvertently randomized into study and did not receive study drug. Last observation carried forward method was used for patients without Month 4 data for any reason and who used rescue medication or any other glucose lowering agents other than metformin. | Posted | Least Squares Mean | Standard Error | pmol*hour/L | Baseline, Month 4 |
| |||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | The full analysis set included all randomized patients except for mis-randomized patients who inadvertently randomized into study and did not receive study drug. Last observation carried forward method was used for patients without Month 4 data for any reason and who used rescue medication or any other glucose lowering agents other than metformin. | Posted | Least Squares Mean | Standard Error | mmol/L | Baseline, Month 4 |
| |||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | The full analysis set included all randomized patients except for mis-randomized patients who inadvertently randomized into study and did not receive study drug. Last observation carried forward method was used for patients without Month 4 data for any reason and who used rescue medication or any other glucose lowering agents other than metformin. | Posted | Least Squares Mean | Standard Error | mmol/L | Baseline, Month 4 |
| |||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | The full analysis set included all randomized patients except for mis-randomized patients who inadvertently randomized into study and did not receive study drug. Last observation carried forward method was used for patients without Month 4 data for any reason and who used rescue medication or any other glucose lowering agents other than metformin. | Posted | Least Squares Mean | Standard Error | nmol/L | Baseline, Month 4 |
| |||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | The full analysis set included all randomized patients except for mis-randomized patients who inadvertently randomized into study and did not receive study drug. Last observation carried forward method was used for patients without Month 4 data for any reason and who used rescue medication or any other glucose lowering agents other than metformin. | Posted | Least Squares Mean | Standard Error | pmol/L | Baseline, Month 4 |
| |||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | The full analysis set included all randomized patients except for mis-randomized patients who inadvertently randomized into study and did not receive study drug. Last observation carried forward method was used for patients without Month 4 data for any reason and who used rescue medication or any other glucose lowering agents other than metformin. | Posted | Least Squares Mean | Standard Error | pmol/min/m²/mmol *hour/L | Baseline, Month 4 |
| |||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | The full analysis set included all randomized patients except for mis-randomized patients who inadvertently randomized into study and did not receive study drug. Last observation carried forward method was used for patients without Month 4 data for any reason and who used rescue medication or any other glucose lowering agents other than metformin. | Posted | Least Squares Mean | Standard Error | pmol/min/m² | Baseline, Month 4 |
| |||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | The full analysis set included all randomized patients except for mis-randomized patients who inadvertently randomized into study and did not receive study drug. Last observation carried forward method was used for patients without Month 4 data for any reason and who used rescue medication or any other glucose lowering agents other than metformin. | Posted | Least Squares Mean | Standard Error | mmol/L | Baseline, Month 4 |
| |||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | The full analysis set included all randomized patients except for mis-randomized patients who inadvertently randomized into study and did not receive study drug. Last observation carried forward method was used for patients without Month 4 data for any reason and who used rescue medication or any other glucose lowering agents other than metformin. | Posted | Least Squares Mean | Standard Error | mmol/L | Baseline, Month 4 |
| |||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | The full analysis set included all randomized patients except for mis-randomized patients who inadvertently randomized into study and did not receive study drug. Last observation carried forward method was used for patients without Month 4 data for any reason and who used rescue medication or any other glucose lowering agents other than metformin. | Posted | Least Squares Mean | Standard Error | mmol/L | Baseline, Month 4 |
| |||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | The full analysis set included all randomized patients except for mis-randomized patients who inadvertently randomized into study and did not receive study drug. Last observation carried forward method was used for patients without Month 4 data for any reason and who used rescue medication or any other glucose lowering agents other than metformin. | Posted | Least Squares Mean | Standard Error | pmol/L | Baseline, Month 4 |
| |||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | The full analysis set included all randomized patients except for mis-randomized patients who inadvertently randomized into study and did not receive study drug. Last observation carried forward method was used for patients without Month 4 data for any reason and who used rescue medication or any other glucose lowering agents other than metformin. | Posted | Least Squares Mean | Standard Error | percentage of beta cell function | Baseline, Month 4 |
| |||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | The full analysis set included all randomized patients except for mis-randomized patients who inadvertently randomized into study and did not receive study drug. Last observation carried forward method was used for patients without Month 4 data for any reason and who used rescue medication or any other glucose lowering agents other than metformin. | Posted | Least Squares Mean | Standard Error | percentage of insulin resistance | Baseline, Month 4 |
| |||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | The full analysis set included all randomized patients except for mis-randomized patients who inadvertently randomized into study and did not receive study drug. Last observation carried forward method was used for patients without Month 4 data for any reason and who used rescue medication or any other glucose lowering agents other than metformin. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline, Month 4 |
| |||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | The full analysis set included all randomized patients except for mis-randomized patients who inadvertently randomized into study and did not receive study drug. Last observation carried forward method was used for patients without Month 4 data for any reason and who used rescue medication or any other glucose lowering agents other than metformin. | Posted | Least Squares Mean | Standard Error | log (mg/L) | Baseline, Month 4 |
| |||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | The full analysis set included all randomized patients except for mis-randomized patients who randomized in error, did not receive study drug. LOCF method was used for patients without Month 4 data for any reason and who used rescue drug or any other glucose lowering agents other than metformin. 'n' = patients with baseline and endpoints data. | Posted | Least Squares Mean | Standard Error | percent change | Baseline, Month 4 |
| |||||||||||||||||||||||||||||||||||||||
| Primary | 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. | The benefit of canakinumab for the treatment of patients with type 2 diabetes mellitus in combination with metformin was inadequate to continue patients into Period IV in the present study, and therefore decided to terminate the study during Period III. | Posted | Least Squares Mean | Standard Error | pmol/min/m2/mmol* hour/L | Baseline, Over Month 4 |
|
Patients have been exposed up to 15 months (median exposure however was at about 6 months)
The data reported below in the safety tables are from the pooled Phase II and Phase III data.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Canakinumab 5 mg + Metformin | 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. | 3 | 93 | 9 | 93 | ||
| EG001 | Canakinumab 15 mg + Metformin | 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. | 1 | 95 | 9 | 95 | ||
| EG002 | Canakinumab 50 mg + Metformin | 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. | 5 | 92 | 15 | 92 | ||
| EG003 | Canakinumab 150 mg + Metformin | Experimental: Canakinumab 150 mg + Metformin 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. | 7 | 92 | 8 | 92 | ||
| EG004 | Placebo + Metformin | 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). | 8 | 179 | 26 | 179 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute left ventricular failure | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Angina pectoris | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Angina unstable | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Cardiac failure congestive | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Coronary artery disease | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Myocardial infarction | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Colonic polyp | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Inguinal hernia | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA | Systematic Assessment |
| |
| Cholecystitis | Hepatobiliary disorders | MedDRA | Systematic Assessment |
| |
| Breast abscess | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Gastroenteritis bacterial | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Graft infection | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Urosepsis | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Multiple fractures | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
| |
| Hepatic enzyme increased | Investigations | MedDRA | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
| |
| Osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
| |
| Rotator cuff syndrome | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
| |
| Basal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA | Systematic Assessment |
| |
| Haemorrhagic stroke | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Ischaemic cerebral infarction | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Calculus ureteric | Renal and urinary disorders | MedDRA | Systematic Assessment |
| |
| Calculus urinary | Renal and urinary disorders | MedDRA | Systematic Assessment |
| |
| Renal failure acute | Renal and urinary disorders | MedDRA | Systematic Assessment |
| |
| Renal mass | Renal and urinary disorders | MedDRA | Systematic Assessment |
| |
| Benign prostatic hyperplasia | Reproductive system and breast disorders | MedDRA | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA | Systematic Assessment |
|
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Novartis Pharmaceuticals | 862-778-8300 |
| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C541220 | canakinumab |
| D008687 | Metformin |
| ID | Term |
|---|---|
| D001645 | Biguanides |
| D006146 | Guanidines |
| D000578 | Amidines |
| D009930 | Organic Chemicals |
Not provided
Not provided
| Lost to Follow-up |
|
| Administrative problems |
|
| Male |
|
| Death |
|
| Serious Adverse Events |
|
| OG001 | Canakinumab 15 mg + Metformin | 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. |
| OG002 | Canakinumab 50 mg + Metformin | 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. |
| OG003 | Canakinumab 150 mg + Metformin | 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. |
| OG004 | Placebo + Metformin | 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). |
|
|
| OG001 | Canakinumab 15 mg + Metformin | 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. |
| OG002 | Canakinumab 50 mg + Metformin | 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. |
| OG003 | Canakinumab 150 mg + Metformin | 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. |
| OG004 | Placebo + Metformin | 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). |
|
|
| OG001 | Canakinumab 15 mg + Metformin | 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. |
| OG002 | Canakinumab 50 mg + Metformin | 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. |
| OG003 | Canakinumab 150 mg + Metformin | 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. |
| OG004 | Placebo + Metformin | 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). |
|
|
| OG001 | Canakinumab 15 mg + Metformin | 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. |
| OG002 | Canakinumab 50 mg + Metformin | 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. |
| OG003 | Canakinumab 150 mg + Metformin | 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. |
| OG004 | Placebo + Metformin | 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). |
|
|
| OG001 | Canakinumab 15 mg + Metformin | 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. |
| OG002 | Canakinumab 50 mg + Metformin | 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. |
| OG003 | Canakinumab 150 mg + Metformin | 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. |
| OG004 | Placebo + Metformin | 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). |
|
|
| OG001 | Canakinumab 15 mg + Metformin | 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. |
| OG002 | Canakinumab 50 mg + Metformin | 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. |
| OG003 | Canakinumab 150 mg + Metformin | 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. |
| OG004 | Placebo + Metformin | 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). |
|
|
| OG001 | Canakinumab 15 mg + Metformin | 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. |
| OG002 | Canakinumab 50 mg + Metformin | 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. |
| OG003 | Canakinumab 150 mg + Metformin | 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. |
| OG004 | Placebo + Metformin | 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). |
|
|
| OG001 | Canakinumab 15 mg + Metformin | 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. |
| OG002 | Canakinumab 50 mg + Metformin | 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. |
| OG003 | Canakinumab 150 mg + Metformin | 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. |
| OG004 | Placebo + Metformin | 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). |
|
|
| OG001 | Canakinumab 15 mg + Metformin | 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. |
| OG002 | Canakinumab 50 mg + Metformin | 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. |
| OG003 | Canakinumab 150 mg + Metformin | 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. |
| OG004 | Placebo + Metformin | 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). |
|
|
| OG001 | Canakinumab 15 mg + Metformin | 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. |
| OG002 | Canakinumab 50 mg + Metformin | 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. |
| OG003 | Canakinumab 150 mg + Metformin | 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. |
| OG004 | Placebo + Metformin | 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). |
|
|
| OG001 | Canakinumab 15 mg + Metformin | 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. |
| OG002 | Canakinumab 50 mg + Metformin | 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. |
| OG003 | Canakinumab 150 mg + Metformin | 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. |
| OG004 | Placebo + Metformin | 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). |
|
|
| OG001 | Canakinumab 15 mg + Metformin | 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. |
| OG002 | Canakinumab 50 mg + Metformin | 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. |
| OG003 | Canakinumab 150 mg + Metformin | 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. |
| OG004 | Placebo + Metformin | 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). |
|
|
| Canakinumab 15 mg + Metformin |
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. |
| OG002 | Canakinumab 50 mg + Metformin | 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. |
| OG003 | Canakinumab 150 mg + Metformin | 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. |
| OG004 | Placebo + Metformin | 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). |
|
|
| Canakinumab 15 mg + Metformin |
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. |
| OG002 | Canakinumab 50 mg + Metformin | 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. |
| OG003 | Canakinumab 150 mg + Metformin | 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. |
| OG004 | Placebo + Metformin | 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). |
|
|
| OG001 | Canakinumab 15 mg + Metformin | 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. |
| OG002 | Canakinumab 50 mg + Metformin | 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. |
| OG003 | Canakinumab 150 mg + Metformin | 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. |
| OG004 | Placebo + Metformin | 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). |
|
|
| OG001 | Canakinumab 15 mg + Metformin | 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. |
| OG002 | Canakinumab 50 mg + Metformin | 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. |
| OG003 | Canakinumab 150 mg + Metformin | 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. |
| OG004 | Placebo + Metformin | 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). |
|
|
| OG001 | Canakinumab 15 mg + Metformin | 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. |
| OG002 | Canakinumab 50 mg + Metformin | 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. |
| OG003 | Canakinumab 150 mg + Metformin | 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. |
| OG004 | Placebo + Metformin | 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). |
|
|
| Canakinumab 15 mg + Metformin |
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. |
| OG002 | Canakinumab 50 mg + Metformin | 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. |
| OG003 | Canakinumab 150 mg + Metformin | 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. |
| OG004 | Placebo + Metformin | 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). |
|
|
| OG001 | Canakinumab 15 mg + Metformin | 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. |
| OG002 | Canakinumab 50 mg + Metformin | 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. |
| OG003 | Canakinumab 150 mg + Metformin | 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. |
| OG004 | Placebo + Metformin | 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). |
|
|
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.
| OG002 | Canakinumab 50 mg + Metformin | 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. |
| OG003 | Canakinumab 150 mg + Metformin | 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. |
| OG004 | Placebo + Metformin | 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). |
|