E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Type 2 Diabetes Mellitus with Moderate Renal Impairment |
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E.1.1.1 | Medical condition in easily understood language |
Type 2 Diabetes Mellitus with Moderate Renal Impairment |
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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 | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10062237 |
E.1.2 | Term | Renal impairment |
E.1.2 | System Organ Class | 10038359 - Renal and urinary disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045242 |
E.1.2 | Term | Type II 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 |
In subjects with inadequately-controlled T2DM and moderate renal insufficiency:
• To assess the effect of canagliflozin relative to placebo on hemoglobin A1c (HbA1c) after 26 weeks of treatment
• To assess the safety and tolerability of canagliflozin
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E.2.2 | Secondary objectives of the trial |
After 26 weeks of treatment, to assess the effects of canagliflozin relative to placebo on: Fasting plasma glucose (FPG); Proportion of subjects with an HbA1c<7%; Systolic and diastolic blood pressure; Proportion of subjects receiving rescue therapy and time to rescue therapy; Fasting plasma lipids; Body weight, and Renal function (eGFR and ACR)
After 52 weeks of treatment, to assess the effect of canagliflozin relative to placebo on: Glycemic control (HbA1c and FPG); Proportion of subjects with HbA1c <7%; Systolic and diastolic blood pressure; Proportion of subjects receiving rescue therapy and time to rescue therapy; Fasting plasma lipids; Body weight; Renal function (eGFR and ACR)
Over 26 weeks of treatment, to assess exposure-response relationships of canagliflozin using a population pharmacokinetic (PK) approach.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Patients with T2DM not on an AHA or on any AHA in monotherapy or combination therapy (including oral or non oral agents)
•Patients with reduced kidney function |
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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
•Have proliferative diabetic retinopathy for which treatment is planned during the course of the study
•Kidney disease that required treatment with immunosuppressive therapy, history of dialysis or kidney transplant, presence of nephrotic syndrome (eg, severe proteinuria with hypoalbuminemia and/or edema), or inflammatory kidney disease
•Receiving anti hypertensive or anti-hyperlipidemic therapy not on a stable regimen
•History of a severe hypoglycemic episode within 6 months before screening |
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E.5 End points |
E.5.1 | Primary end point(s) |
•To assess the effect of canagliflozin relative to placebo on hemoglobin A1c (HbA1c) and to assess the safety and tolerability of canagliflozin. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The effect of canagliflozin will be assessed after 26 weeks of treatment with study drug. The safety and tolerability of canagliflozin will be assessed from time of signed informed consent to study end (includes up to 30 days following the last dose). |
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E.5.2 | Secondary end point(s) |
1) To assess exposure-response relationships of canagliflozin using a population pharmacokinetic approach.
2) To assess the effects of canagliflozin relative to placebo on fasting plasma glucose.
3) To assess the effects of canagliflozin relative to placebo on fasting plasma lipids, body weight, systolic and diastolic blood pressure, the proportion of patients achieving an HbA1c <7, and the proportion of patients receiving rescue therapy.
4) To assess the effects of canagliflozin relative to placebo on renal function.
5) To assess the effects of canagliflozin relative to placebo on glycemic control. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) Over 26 weeks of treatment
2) After 26 weeks of treatment
3) After 26 and 52 weeks of treatment
4) After 26 and 52 weeks of treatment
5) After 52 weeks of treatment |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
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 | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 38 |
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 |
Australia |
Belgium |
Brazil |
Canada |
France |
Germany |
India |
Italy |
Korea, Republic of |
Latvia |
Malaysia |
Mexico |
Poland |
Romania |
Russian Federation |
South Africa |
Spain |
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. |
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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 | 11 |
E.8.9.1 | In the Member State concerned days | 13 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 26 |