Resumen

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.

Elegibilidad

Edad mínima: 18 YearsEdad máxima: 74 YearsSexo: ALL

Criterios de inclusión

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)

Criterios de exclusión

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.

Intervenciones

drug

Placebo

Placebo lyophilized cake will be reconstituted and then used to dilute the 25mg or 150mg solutions to make 5mg, 15mg and 50mg injections.

drug

Canakinumab

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.

drug

Metformin

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.

Ubicaciones

DIM Clinica Privada

Buenos Aires, Buenos Aires, Argentina

Centro Medico Viamonte

Buenos Aires, Buenos Aires, Argentina

Consultorios Asociados de Endocrinologia

Buenos Aires, Buenos Aires, Argentina

Clinica de Fracturas y Ortopedia

Mar del Plata, Buenos Aires, Argentina

Hospital Juan Ramon Vidal

Corrientes, Corrientes Province, Argentina

Instituto de Investigaciones Biomedicas

Santa Fe, Santa Fe Province, Argentina

Centro de Investigaciones Clinicas del Litoral

Santa Fe, Santa Fe Province, Argentina

Novartis Investigative Site

Rosario Santa Fe, Argentina

Dose Finding, Safety and Efficacy of Monthly Subcutaneous Canakinumab Administration for the Treatment of Hyperglycemia in Metformin Monotherapy Treated Type 2 Diabetic Patients: a Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Placebo

Canakinumab

Metformin

Ubicaciones

DIM Clinica Privada

Centro Medico Viamonte

Consultorios Asociados de Endocrinologia

Clinica de Fracturas y Ortopedia

Hospital Juan Ramon Vidal

Instituto de Investigaciones Biomedicas

Centro de Investigaciones Clinicas del Litoral

Novartis Investigative Site

Patrocinadores