Subjects with T2DM with inadequate glycemic control on a maximally effective dose of metformin in monotherapy MedDRA version: 13.1 Level: LLT Classification code 10063624 Term: Type II diabetes mellitus inadequate control System Organ Class: 10027433 - Metabolism and nutrition disorders
Conditions
Interventions
Product Name: Canagliflozin
Product Code: JNJ-28431754
Pharmaceutical Form: Capsule
INN or Proposed INN: Canagliflozin
CAS Number: 842133-18-0
Current Sponsor code: JNJ-28431754
Concentration unit: mg
Sponsors
Janssen Cilag International NV
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Be a man or woman =18 and =80 years of age with T2DM and on metformin monotherapy at a stable protocol-specified dose (=2,000 mg/day [or =1,500 mg/day, if unable to tolerate a higher dose]) for at least 8 weeks immediately prior to screening and have 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) 2. 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. 5. Women of childbearing potential must have a negative urine ß-human chorionic gonadotropin (ß-hCG) pregnancy test at screening and baseline (predose, Day 1) 6. Willing and able to adhere to the prohibitions and restrictions specified in this protocol 7. 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 8. Adequate compliance with the run-in period study procedures, including performance of the fasting SMBG measurements (completed at least 3 or more fasting SMBG measurements per week) with appropriate diary entries, and =80% compliance (by pill count) with singleblind placebo capsules Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 200 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 70
Exclusion criteria
Exclusion criteria: Diabetes-related or Metabolic 1. Has a history of diabetic ketoacidosis, T1DM, pancreas or beta-cell transplantation, or diabetes secondary to pancreatitis or pancreatectomy 2. Has 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 3. Has proliferative diabetic retinopathy for which treatment is planned during the course of the study 4. Has a 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. 5. Has history of hereditary glucose-galactose malabsorption or primary renal glucosuria 6. Has 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 7. Is on either a PPAR? agonist (eg, a thiazolidinedione (TZD) [pioglitazone or rosiglitazone]), ongoing insulin therapy, another SGLT2 inhibitor, or any AHA (including agents such as colesevelam and bromocriptine that have indications in some regions for treatment of T2DM) other than metformin, 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. 8. Has 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 9. Has 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. 10. 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 11. Has findings on 12-lead ECG that would require urgent diagnostic evaluation or intervention (eg, new clinically important arrhythmia or conduction disturbance) 12. 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 (on a stable regimen for at least 4 weeks before Day 1 to be eligible). Gastrointestinal 13. Has 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. 14. Has history of prior bariatric surgical procedure within 3 years before the screening visit. Note: subjects with bariatric surgery more than 3 years prior to screening must be at a stable weight to be eligible to participate. Laboratory 15. Estimated glomerular filtration rate (eGFR) (as determined by central laboratory) <55 mL/min/1.73 m2 (or eGFR <60 mL/min
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: After 18 weeks of treatment: -To assess the effect of canagliflozin 150 mg administered twice daily on HbA1c relative to placebo - To assess the safety and tolerability of canagliflozin;Primary end point(s): The primary efficacy endpoint will be the change in HbA1c from baseline to Week 18.;Timepoint(s) of evaluation of this end point: week 18;Secondary Objective: After 18 weeks of treatment: - To assess the effect of canagliflozin 50 mg administered twice daily on HbA1c relative to placebo - To assess the effect of canagliflozin 150 mg administered twice daily, or canagliflozin 50 mg administered twice daily, on the following parameters relative to placebo: – Fasting plasma glucose (FPG) – Body weight – Proportion of subjects with HbA1c <7.0% and <6.5% – 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 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key secondary endpoints will include the change from baseline to Week 18 in FPG, and percent change to Week 18 from baseline in body weight. The proportion of subjects with HbA1c <7.0% at Week 18 will also be a key secondary endpoint. Additional efficacy endpoints will include change in fasting lipid profile and in systolic and diastolic blood pressure at Weeks 18. Proportion of subjects with HbA1c <6.5% at Week 18 will also be an endpoint of interest.;Timepoint(s) of evaluation of this end point: Week 18 | — |
Countries
Canada, Czech Republic, Mexico, Russian Federation, Slovakia, United States
Contacts
Public ContactClinical Registry Group
Janssen Cilag International NV
Outcome results
None listed