Canagliflozin (Invokana™) vs. Standard Dual Therapy Regimen for T2DM During Ramadan

• Status: Completed
• Trial end date: 2018-09-13
• Target enrollment: 0
• Participant gender: All

Summary

This study aims to determine if the addition of Canagliflozin (Invokana™) therapy to monotherapy of metformin is more effective at achieving the double composite endpoint of a reduction in HbA1c (≥ 0.3%) and weight loss (≥1kg) 3-4 weeks post-Ramadan. The study will also include patients currently on dual therapy, specifically metformin plus a sulphonylurea, pioglitazone or repaglinide to determine whether switching to metformin plus Canagliflozin (Invokana™) is more effective at achieving the composite endpoint compared to those remaining on previous dual therapy. There are a number of secondary outcomes including weight loss, rates of hypoglycaemia, blood pressure and a number of biochemical endpoints.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Leicester
• Collaborator: University Hospital Birmingham
• Treatments: Canagliflozin; Gliclazide; Glimepiride; Metformin; Pioglitazone; Repaglinide

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 or DPP-4 inhibitor for ≥ 8 weeks prior to enrolment)

4. HbA1c between 6.6 - 11% (49mmol/mol - 97mmol/mol) at the screening visit

5. Individuals intending to fast during the holy month of Ramadan

Exclusion Criteria

1. Unable, in the opinion of the Investigator, and unwilling 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 ≤6.5 and ≥11.1%

5. Individuals not intending to fast 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) <60ml/min/1.73m2 at screening

11. Have serum creatinine levels >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, 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, pioglitazone and/or DPP-4 inhibitors

26. Have severe irritable bowel disorder

27. Have hereditary glucose-galactose malabsorption

28. Have primary renal glycosuria

29. Patients who have participated in another study of an investigational medicinal product in the last 3 months

30. High risk of bone fracture (undiagnosed osteoporosis) as determined by the WHO FRAX tool

31. Evidence of excessive and compulsive drinking of alcohol i.e. alcohol abuse as determined by the Fast Alcohol Screening Test (FAST)

32. Individuals on a severe calorie restricted diet <800cals/day

33. Has a surgical procedure booked in the next 12 months

34. Has a history of chronic pancreatitis

35. Has latent autoimmune diabetes in adults (LADA)

36. Individuals on loop diuretics

37. Any contraindication to the IMP