Type 2 Diabetes Mellitus MedDRA version: 18.1 Level: LLT Classification code 10045242 Term: Type II diabetes mellitus System Organ Class: 100000004861
Conditions
Interventions
Trade Name: Invokana
Product Name: Canagliflozin
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Canagliflozin
Concentratio
Sponsors
University of Leicester
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Able, in the opinion of the Investigator, and willing to give informed consent 2. Age = 25 years old 3. Established T2DM (= 3 months) on stable dose monotherapy (metformin only for = 8 weeks prior to enrolment) OR stable dose dual therapy (metformin plus either repaglinide, a sulphonylurea or pioglitazone for = 8 weeks prior to enrolment) 4. HbA1c between 7 – 10.5% (53 - 91mmol/mol) if on monotherapy OR between 6.5 - 9.5% (48 – 80mmol/mol) if on dual therapy at the screening visit 5. Individuals intending to fast for a minimum of 10 consecutive days during the holy month of Ramadan Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 100 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 16
Exclusion criteria
Exclusion criteria: 1. Unable, in the opinion of the Investigator, and unable to provide informed consent 2. Aged = 25 years old 3. Established T2DM (= 3 months) on medication for fewer than 8 weeks prior to enrolment 4. HbA1c =7 and =10.5% (if on monotherapy) and =6.5 and =9.5% (if on dual therapy) 5. Individuals not intending to fast for a minimum of 10 consecutive days during the holy month of Ramadan 6. Females of childbearing potential who are pregnant, breast-feeding or intend to become pregnant or are not using adequate contraceptive methods. The latter includes avoiding sex, hormonal prescription oral contraceptives, contraceptive injections, contraceptive patch, intrauterine device, double-barrier method (e.g., condoms, diaphragm, or cervical cap with spermicidal foam, cream, or gel), or male partner sterilization, 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. Furthermore, 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 pregnancy test at baseline. 7. Suffer from terminal illness 8. Have renal disease that requires immunosuppressive therapy, dialysis or transplant 9. Have nephrotic syndrome or inflammatory renal disease 10. Have an estimated glomerular filtration rate (eGFR) 132.6µmol/L for men or >123.8µmol/L for women 12. Impaired liver function (ALAT = 2.5 times upper limit of normal) 13. Known Hepatitis B antigen or Hepatitis C antibody positive 14. Clinically significant active cardiovascular disease (including history of myocardial infarction, unstable angina, previous revascularization procedure or cerebrovascular accident) within the past 6 months before screening 15. Have uncontrolled hypertension (defined as systolic blood pressure =180mm/Hg and diastolic =100mm/Hg in the supine position after >5minutes rest with confirmed compliance to antihypertensive medication) 16. Heart failure (NYHA class III and IV) at the discretion of the investigator 17. Previous history of recurrent major hypoglycaemia as judged by the study clinician 18. Known or suspected allergy to the study product 19. Receipt of any investigational drug within four weeks prior to this study 20. Has had previous treatment with a GLP-1 receptor agonist, DPP-IV inhibitor, insulin, or another SGLT2 inhibitor within 12 weeks of screening 21. Have severe and enduring mental health problems 22. Are not primarily responsible for their own care 23. Are receiving insulin therapy 24. Type 1 diabetes 25. Any contraindication to sulphonylureas, repaglinide and/or pioglitazone 26. Have severe irritable bowel disorder 27. Have hereditary glucose-galactose malabsorption 28. Have primary renal glycosuria
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): The primary objective is to achieve the double composite endpoint of a reduction in HbA1c (= 0.3%) and weight loss (=1kg) 3-4 weeks post-Ramadan.;Timepoint(s) of evaluation of this end point: Between baseline and 3-4 weeks post Ramadan.;Main Objective: The primary objective is to achieve the double composite endpoint of a reduction in HbA1c (= 0.3%) and weight loss (=1kg) 3-4 weeks post-Ramadan.; Secondary Objective: The main secondary outcome is a triple composite endpoint of a reduction or maintenance of HbA1c, reduction in weight (= 1kg) and no hypoglycaemic events between baseline and 3-4 weeks post-Ramadan. Further secondary outcomes are listed below. These outcomes will be measured at each time point described in A13 below and a comparison calculated between treatment groups. 1. Mean change in HbA1c level 2. Mean change in fructosamine 3. Mean change in body weight 4. Mean change in systolic blood pressure 5. Mean change in diastolic blood pressure 6. Mean changes in total cholesterol 7. Mean changes in HDL cholesterol 8. Mean change LDL cholesterol 9. Mean change in triglycerides 10. Mean change in treatment satisfaction (DTSQ) 11. Mean change in IPAQ score (self-reported activity levels) 12. Mean change in light, moderate, and vigorous intensity physical activity as determined by GENEActiv 13. Mean change in total volume of movement as determined by GENEActiv 14. Me | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The main secondary outcome is a triple composite endpoint of a reduction and/or maintenance of HbA1c, reduction in body weight and no hypoglycaemic events between baseline and 3-4 weeks post-Ramadan. Further secondary outcomes are listed below. These outcomes will be measured at each time-point and a comparison calculated between treatment groups; (1) Mean change HbA1c level (2) Mean change in fructosamine (3) Mean change in body weight (4) Mean change in systolic blood pressure (5) Mean change in diastolic blood pressure (6) Mean changes in total cholesterol, LDLc, HDLc, and Triglycerides (7) Mean change in treatment satisfaction (DTSQ) (8) Mean change in IPAQ score (self-reported activity levels) (9) Mean change in light, moderate, and vigorous intensity physical activity as determined by the GENEActiv (10) Mean change in total volume of movement as determined by the GENEActiv (12) Mean change in frequency of self-measured hypoglycaemic events recorded in glucose diaries and severe hypoglycaemic events (13) Median (IQR) number of self-measured hypoglycaemic episodes per patient (14) Median (IQR) number of severe hypoglycaemic episodes per patient (15) Incidence rate of self-measured hypoglycaemia per person year (incidence rate ratio (IRR) 16) Incident rate of severe hypoglycaemia per person year (incidence rate ratio (IRR)) Double composite end-points (1) Double composite endpoint of weight loss and no severe hypoglycaemic events (2) Double composite endpoint of no weight-gain and a reduction in number of self-measured hypoglycaemic events +/- symptoms (3) Double composite endpoint of improved HbA1c and no severe hypoglycaemic events | — |
Countries
United Kingdom
Contacts
Public ContactDr Emer Brady
University Hospitals of Leicester NHS Trust
Outcome results
None listed