E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067585 |
E.1.2 | Term | Type 2 diabetes mellitus |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
• To assess the effect of the addition of treatment with canagliflozin compared with the addition of treatment with sitagliptin on HbA1c after 52 weeks.
• To assess the safety and tolerability of canagliflozin
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E.2.2 | Secondary objectives of the trial |
After 52 weeks of treatment, to assess the effect of the addition of treatment with canagliflozin compared with the addition with sitagliptin on: Body weight; Fasting plasma glucose (FPG); Proportion of subjects with hemoglobin A1c (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; Time to and proportion of subjects discontinued early for meeting glycemic withdrawal criteria, and Fasting measures of beta-cell function (ie, HOMA-B, proinsulin to insulin ratio)
--For complete listing, please refer to 'Secondary Obejctives' section of the protocol.
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
The frequently sampled mixed-meal tolerance test (FS-MMTT) substudy is contained in the main protocol and part of secondary objectives. After 52 weeks of treatment, a subset of subjects (~20% of total subjects) will undergo a FS-MMTT, to assess the effect of the addition of treatment with canagliflozin compared with the addition of treatment with sitagliptin. |
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E.3 | Principal inclusion criteria |
• All patients must have a diagnosis of T2DM and be currently treated with metformin and sulphonylurea
• Patients in the study must have a HbA1c between >=7 and <=10.5% and a fasting plasma glucose (FPG) <300 mg/dL (16.7 mmol/L) |
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E.4 | Principal exclusion criteria |
History of diabetic ketoacidosis, type 1 diabetes mellitus (T1DM), pancreas or beta cell transplantation, or diabetes secondary to
pancreatitis or pancreatectomy, or a severe hypoglycemic episode within
6 months before screening |
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E.5 End points |
E.5.1 | Primary end point(s) |
The effect of canagliflozin compared with sitagliptin on hemoglobin A1c (HbA1c) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After 52 weeks of treatment |
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E.5.2 | Secondary end point(s) |
1) The effect of canagliflozin compared with sitagliptin on body weight
2) The effect of canagliflozin compared with sitagliptin on fasting plasma glucose (FPG)
3) The effect of canagliflozin compared with sitagliptin on systolic blood pressure
4) The effect of canagliflozin compared with sitagliptin on
triglycerides
5) The effect of canagliflozin compared with sitagliptin on highdensity lipoprotein cholesterol (HDL-C) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-5: After 52 weeks of treatment with study drug |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Single blind week 2 run in then double blind randomisation. |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 66 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Austria |
Brazil |
Canada |
France |
Germany |
India |
Israel |
Korea, Republic of |
Malaysia |
Netherlands |
New Zealand |
Poland |
Singapore |
Ukraine |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the trial is the last visit of the last subject undergoing the trial as provided in the protocol. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |