Type 2 Diabetes Mellitus With Inadequate Glycemic Control on Metformin Monotherapy MedDRA version: 12.1 Level: LLT Classification code 10067585 Term: Type 2 diabetes mellitus
Conditions
Interventions
Product Name: canagliflozin
Product Code: JNJ-28431754
Pharmaceutical Form: Over encapsulated tablet
INN or Proposed INN: canagliflozin
Sponsors
Janssen-Cilag International NV
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Man or woman =18 and =80 years of age with T2DM who meet 1 of the following 4 criteria: On metformin IR monotherapy at a stable protocol-specified dose* for at least 8 weeks before screening and has an HbA1c of =7.0% and =10.5% at screening (or at Week -2, if screening measurement is more than 3 weeks before Week -2) or – On metformin ER monotherapy at a protocol-specified dose* with an HbA1c of =7.0% and =10.5% at screening and has a Week -2 visit HbA1c of =7.0% and =10.5%, after at least 8 weeks on a stable protocol-specified dose* of metformin IR or – On metformin monotherapy (IR or ER) at a dose 45 years of age with amenorrhea for at least 18 months, or ? >45 years of age with amenorrhea for at least 6 months and 40 IU/mL, or – surgically sterile (have had a hysterectomy, bilateral oophorectomy, or tubal ligation) or otherwise be incapable of pregnancy, or – heterosexually active and practicing a highly effective method of birth control, including hormonal prescription oral contraceptives, contraceptive injections, contraceptive patch, intrauterine device, double-barrier method (eg, condoms, diaphragm, or cervical cap with spermicidal foam, cream, or gel), or male partner sterilization, and consistent with local regulations regarding use of birth control methods for subjects participating in clinical trials, for the duration of their participation in the study, or – not heterosexually active Note: subjects who are not heterosexually active at screening must agree to utilize a highly effective method of birth control if they become heterosexually active during their participation in the study. • Women of childbearing potential must have a negative urine ß human chorionic gonadotropin (ß hCG) pregnancy test at screening and baseline (predose,
Exclusion criteria
Exclusion criteria: Diabetes-related or Metabolic •History of diabetic ketoacidosis, T1DM, pancreas or beta-cell transplantation, or diabetes secondary to pancreatitis or pancreatectomy •Repeated (ie, 2 or more over a 1 week period) FPG and/or fasting SMBG glucose measurements =270 mg/dL (15 mmol/L) during the pre-treatment phase, despite reinforcement of diet and exercise counseling •Have proliferative diabetic retinopathy for which treatment is planned during the course of the study •History of 1 or more severe hypoglycemic episode within 6 months before screening •History of hereditary glucose-galactose malabsorption or primary renal glucosuria •Ongoing, inadequately controlled thyroid disorder (eg, subject has a known thyroid stimulating hormone [TSH] value that is either 10 mIU/L) •On either a PPAR? agonist (eg, a thiazolidinedione (TZD) [pioglitazone or rosiglitazone]) ongoing insulin therapy, another SGLT2 inhibitor, or any other AHA (including agents such as colesevelam and bromocriptine that have indications in some regions for treatment of T2DM) except as specified in the study inclusion criteria within 12 weeks before the screening visit •Ongoing eating disorder or significant weight loss or weight gain within 12 weeks before the screening visit, defined as an increase or decrease of 5% in body weight based upon clinic-based measurement or, if not available, subject report Renal/Cardiovascular •Renal disease that required treatment with immunosuppressive therapy or a history of dialysis or renal transplant. •Myocardial infarction, unstable angina, revascularization procedure (eg, stent or bypass graft surgery), or cerebrovascular accident within 3 months before screening, or revascularization procedure is planned, or subject has a history of New York Heart Association (NYHA) Class III-IV cardiac disease •Findings on 12-lead ECG that would require urgent diagnostic evaluation or intervention (eg, new clinically important arrhythmia or conduction disturbance) •Uncontrolled hypertension (ie, using an average of 3 seated blood pressure readings with a diastolic blood pressure =100 mmHg or systolic blood pressure =160 mmHg) at Week -2. Gastrointestinal •History of hepatitis B surface antigen or hepatitis C antibody positive (unless associated with documented persistently stable/normal range aspartate aminotransferase [AST] and ALT levels), or other clinically active liver disease. •History of prior bariatric surgical procedure within 3 years before the screening visit. Laboratory •Estimated glomerular filtration rate (eGFR) 2.0 times the ULN or total bilirubin >1.5 times the ULN at screening (for elevations in bilirubin: if, in the opinion of the investigator and agree
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To assess the effect of canagliflozin relative to placebo on HbA1c after 26 weeks of treatment • To assess the safety and tolerability of canagliflozin ; Secondary Objective: • Fasting plasma glucose (FPG) • Body weight • Proportion of subjects with HbA1c <7.0% and <6.5% • 2 hour postprandial plasma glucose (2 h PPG) after a standard meal • Fasting plasma lipids (ie, low-density lipoprotein-cholesterol [LDL-C], high-density lipoprotein-cholesterol [HDL-C], total cholesterol, LDL-C to HDL-C ratio, and triglycerides) • Systolic and diastolic blood pressure • Time to rescue therapy and proportion of subjects receiving rescue therapy • Fasting measure of beta-cell function (ie, HOMA-B) After 52 weeks of treatment, to assess the effect of canagliflozin relative to sitagliptin on: • Glycemic control (HbA1c and FPG) • Body weight • Proportion of subjects with HbA1c <7.0% and <6.5% • Fasting plasma lipids (ie, LDL-C, HDL-C, total cholesterol, LDL-C to HDL-C ratio, and triglycerides) • Systolic and diastolic blood pressure... ;Primary end point(s): The primary efficacy endpoint will be the change in HbA1c from baseline to Week 26. | — |
Countries
Bulgaria, Czech Republic, Estonia, Greece, Italy, Latvia, Poland, Portugal, Slovakia, Sweden
Outcome results
None listed