type 2 diabetes mellitus (T2DM) with inadequate glycemic control on combination therapy with metformin and a sulphonylurea (SU) 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
Current Sponsor code: JNJ28431754
Concentration unit: mg milligr
Sponsors
Janssen-Cilag International NV
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Man or woman =18 and =80 years of age with T2DM and currently treated with metformin and an SU • Meet the following HbA1c eligibility criteria: HbA1c Subjects Screening Visit Week -2 Visit On metformin and an SU at protocol-specified doses*a for at least 8 weeks prior to screening =7.0% and =10.5% n/a*b On metformin and an SU, either or both at doses below protocol-specified*a =7.5% =7.0% and =10.5% *a= Metformin =2,000 mg/day (or =1,500 mg/day if intolerant of higher dose*b= If measured at screening more than 3 weeks prior to the Week -2 visit, obtain HbA1c at the Week -2 visit to assess inclusion criterion. • FPG 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, Day 1) • Willing and able to adhere to the prohibitions and restrictions specified in this protocol • Subjects must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study • To participate in the optional pharmacogenomic component of this study, subjects must have signed the informed consent form for pharmacogenomic research indicating willingness to participate in the pharmacogenomic component of the study (where local regulations permit). Refusal to give consent for this component does not exclude a subject from participation in the cl
Exclusion criteria
Exclusion criteria: • 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 measurements =270 mg/dL (15 mmol/L) during the pretreatment 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. Note: a severe hypoglycemic episode is defined as an event that requires the help of another person (refer to Attachment 4, Hypoglycemia: Definitions, Symptoms, and Treatment, for a definition of severe hypoglycemia) • 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) Note: subjects on thyroid hormone replacement therapy must be on stable doses for at least 6 weeks prior to Day 1 • On either a PPAR? agonist (eg, a thiazolidinedione [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 Note: subjects who have been treated with only a single dose of insulin may participate. • 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 disease that required treatment with immunosuppressive therapy or a history of dialysis or renal transplant Note: subjects with a history of treated childhood renal disease, without sequelae, may participate • 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 Note: subjects may have their blood pressure lowering medication regimen adjusted and be re-evaluated to assess this criterion • 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 Note: subjects with bariatric surgery more than 3 years before screening must be at a stable weight to be eligible to participate • Estimated glomerular filtration rate (eGFR) <55 mL/min/1.73 m2 (or <60 mL/min/1.73 m2 if based upon restriction of metformin use in the metformin local label) or serum creatinine =1.4 mg/dL (124 µmol/L) for men and =1.3 mg/dL (115 µmol/L) for women Note: a one-time repeat measurem
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: After 26 weeks of treatment, to assess the effect of canagliflozin relative to placebo on: •Fasting plasma glucose (FPG) •Proportion of subjects with HbA1c <7.0% and <6.5% •Body weight •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 placebo 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 •Time to rescue therapy and proportion of subjects receiving rescue therapy... ;Primary end point(s): The primary efficacy endpoint will be the change in HbA1c from baseline to Week 26. | — |
Countries
Belgium, France, Germany, Hungary, Spain, United Kingdom
Outcome results
None listed