Dose Finding, Safety and Efficacy of Monthly Subcutaneous Canakinumab Administration in Metformin Monotherapy Treated Type 2 Diabetic Patients
Diabetes Mellitus, Type 2
About this trial
This is an interventional treatment trial for Diabetes Mellitus, Type 2 focused on measuring type 2 diabetes, canakinumab
Eligibility Criteria
Inclusion Criteria:
- Patients must have a documented diagnosis of Type 2 diabetes confirmed by World Health Organization (WHO) criteria either a FPG≥ 7.0 mmol/l (126 mg/dl) or an Oral glucose tolerance test (OGTT) test 2-hour PG ≥ 11.1 mmol/l (200 mg/dl).
Patients must:
- be naïve to anti-diabetes drug therapy (except for short term treatment courses with insulin in connection with hospitalization, etc.)
- meet protocol specified Glycosylated hemoglobin / hemoglobin A1c (HbA1c) criteria
- be eligible for metformin monotherapy OR
- be on stable metformin monotherapy treatment for at least three months at Screening
- meet protocol specified HbA1c criteria
- take metformin as their first and only treatment with anti-diabetes drug therapy OR
- be taking an AGI as their first and only anti-diabetes drug therapy (except short term treatment courses with insulin in connection with hospitalizations, etc)
- meet protocol specified HbA1c criteria
- be eligible for metformin monotherapy
- Patients must have a morning fasting plasma glucose result < 180 mg/dl at Visit 3 (Month -1) analyzed by the Central Laboratory.
- Were on a daily dose of metformin ≥ 1000 mg (or less according to local regulations)
Exclusion Criteria:
- Type 1 diabetes, diabetes resulting from pancreatic injury or secondary forms of diabetes.
Any of the following significant laboratory abnormalities:
- Serum Glutamic acid decarboxylase (GAD)-antibody positivity
- Clinically significant Thyroid stimulating hormone (TSH) outside of normal range at Screening
- Renal function indicating high risk metformin use, including serum creatinine concentrations (≥1.5 mg/dL for males, ≥1.4 mg/dL for females) or other evidence of abnormal creatinine clearance.
- Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) > 2 x upper limit of normal (ULN), or total bilirubin > 2 x ULN and/or direct bilirubin > ULN at Screening, confirmed with repeat measure within one week.
- History or current findings of active pulmonary disease as evidenced by a history of positive purified protein derivative (PPD), QuantiFERON-TB Gold (QFT-G), AFB sputum or positive PPD followed by positive chest x-ray or QFT-G, or ongoing antibiotic treatment for latent TB.
- Risk factors for TB as defined in protocol
- Known presence or suspicion of active or recurrent bacterial, fungal or viral infection at the time of enrollment proven or suspected to be related to immunocompromise including HIV or active or recurrent Hepatitis B and Hepatitis C.
- Systemic or local treatment of any immune modulating agent in doses with systemic effects or live vaccinations within 3 months
- Stroke, myocardial infarction, acute coronary syndrome, revascularization procedure or recurrent TIA within the last 6 months.
- Unwillingness to use insulin glargine as the additional medication should glycemic control deteriorate.
Other protocol-defined inclusion/exclusion criteria may apply
Sites / Locations
- Anasazi Internal Medicine
- Whittier Institute of Diabetes
- Novartis Investigative Site
- Novartis Investigative Site
- Orange County Research Center
- Novartis Investigative Site
- Deaconess Clinic
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Diabetes Research Center
- Tri-State Medical Group
- Preferred Primary Care Physicians
- Novartis Investigative Site
- R/D Clinical Research
- Novartis Investigative Site
- Novartis Investigative Site
- Medical Research Initiatives Inc
- Clinica de Fracturas y Ortopedia
- DIM Clinica Privada
- Centro Medico Viamonte
- Consultorios Asociados de Endocrinologia
- Hospital Juan Ramon Vidal
- Novartis Investigative Site
- Instituto de Investigaciones Biomedicas
- Centro de Investigaciones Clinicas del Litoral
- Private Practice - DEMEULEMEESTER
- Novartis Investigative Site
- UZ Brussel
- Novartis Investigative Site
- Praxis F. Franzmann
- emovis GmbH
- Praxis Dr. Stütz
- GWT-TUB GmbH
- Gemeinschaftspraxis und Dialysezentrum Karlstraße
- Asklepios Klinik St. Georg
- Städt. Kankenhaus Nordstadt
- Diabeteszentrum Hohenmölsen
- Johannes Gutenberg-Universität Mainz
- Zentrum für Klinische Forschung Neuwied (ZKSN)
- Praxis Dr. Wunderer
- Praxis Dr. Kosch
- Praxis Dr. Alawi
- Praxis Dr. Klein
- Forschungszentrum Ruhr, KliFoCenter GmbH
- Fővárosi Önkormányzat Péterfy Sándor Utcai Kórház - Rendelőintézet és Baleseti Központ
- Sandor Karolyi Hospital
- Semmelweiss Medical University
- Kenezy Gyula Korhaz
- Szegedi Egyetem
- Zala Megyei Korhaz
- Gokula Metropolis Clinical Research Centre
- Bangalore Diabetes Hospital
- Jnana Sanjeevini Medical Center
- SAMATVAM
- Madras Diabetes Reasearch Foundation
- Amrita Institute of Medical Sciences and Research Center
- Nizam's Institute of Medical Sciences
- Diabetes Thyroid Hormone Research Institute Pvt. Ltd.
- S R Kalla Memorial Gastro & General Hospital
- Pitale Diabetes & Hormone Centre
- Health and Research Centre
- King George Hospital
- National Hospital Organization Nagoya Medical Center
- Kyushu Rosai Hospital
- NHO Yokohama Medical Center
- Musashikoganei Clinic
- Novartis Investigative Site
- Fujikoshi Hospital
- Saiseikai Fukuoka General Hospital
- Kokura Medical Center
- Seino Internal Medicine Clinic
- Geriatrics Research Institute Hospital
- Takagi Hospital
- Sakai Hospital Kinki University School of Medicine
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Instituto Delgado de Investigacion Medica
- Clinica Chiclayo
- Hospital Nacional Cayetano Heredia
- Centro de Investigacion Clinica Trujillo
- Ambulatory of Institute of Nutrition Diseases and Diabetes
- Medical Centre "Sanatatea ta"
- Novartis Investigative Site
- Policlinica Dr. Citu Timisoara
- 203 Maxwell Centre
- Parklands Medical Centre
- St Augustines Medical Centre
- Synapta Clinical Research Centre
- Drs Essack and Mitha
- PE Greenacres Hospital
- 26 Daffodil Street
- Ankara Ataturk Training and Research Hospital
- Gulhane Askeri Tip Akademisi
- Hacettepe University Medical Faculty
- S.B. Yildirim Beyazit Training and Research Hospital
- Istanbul University Cardiology Institute
- Ege University Medical Faculty
- Hayat Tip Merkezi (Hayat Medical Center) Deapartment of Internal Diseases
- Morriston Hospital
- Birmingham Heartlands Hospital
- Royal Bournemouth Hospital
- Rowden Medical Partnership
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Experimental
Experimental
Experimental
Experimental
Placebo Comparator
Canakinumab 5 mg + Metformin
Canakinumab 15 mg + Metformin
Canakinumab 50 mg + Metformin
Canakinumab 150 mg + Metformin
Placebo + 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.
In 4-Month Dose-finding period, patients visited the clinic monthly and had 15 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose >200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy. The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c >7.5% were treated with a daily injection of insulin glargine as add-on therapy.
In 4-Month Dose-finding period, patients visited the clinic monthly and had 50 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose >200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy. The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c >7.5% were treated with a daily injection of insulin glargine as add-on therapy.
In 4-Month Dose-finding period, patients visited the clinic monthly and had 150 mg Canakinumab injected in the clinic at each visit and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations). During this period, patients with consecutive morning fasting glucose >200 mg/dL were treated with a daily injection of insulin glargine as add-on therapy. The intermediate period began after patients completed their 4-month visit and lasted until the primary analysis was completed and the optimal dose was selected. Patients continued on their randomized treatment and made brief visits to the clinic every month. From this point onward, patients with consecutive HbA1c >7.5% were treated with a daily injection of insulin glargine as add-on therapy.
In 4 month dose finding period as well as during intermediate period, patients received one injection of canakinumab matching placebo monthly and continued on a stable dose of metformin ≥ 1000 mg daily (or lower dose if required by local regulations).