E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Type 2 Diabetes Mellitus With Inadequate Glycemic Control With Diet and Exercise |
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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 | 16.1 |
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 | 100000004861 |
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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 co-administration of canagliflozin and metformin XR compared with canagliflozin alone on HbA1c
•To assess the effect of the co-administration of canagliflozin and metformin XR compared with metformin XR alone on HbA1c
•To assess the safety and tolerability of the co-administration of canagliflozin and metformin XR, canagliflozin alone, and metformin XR alone |
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E.2.2 | Secondary objectives of the trial |
• To assess the effect of co-administration of canagliflozin and metformin XR on change from baseline in HbA1c
• To assess the effect of co-administration of canagliflozin and metformin XR relative to baseline and to each agent alone on:
-Fasting plasma glucose (FPG)
-Proportion of subjects with HbA1c <7.0% and <6.5%
-Body weight
-Systolic and diastolic blood pressure
-Fasting plasma lipids (ie, low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein-cholesterol [HDL-C], total cholesterol, non-HDL-C, LDL-C to HDL-C ratio, and triglycerides)
• To assess the effect of canagliflozin alone relative to metformin XR alone on:
- HbA1c
- Body weight
• To assess the effect of canagliflozin relative to baseline on:
- Glycemic control (HbA1c and FPG)
- Proportion of subjects with HbA1c <7.0% and <6.5%
- Body weight
- Systolic and diastolic blood pressure
- Fasting plasma lipids (ie, LDL-C, HDL-C, total cholesterol, non-HDL-C, LDL-C to HDL C ratio, and triglycerides) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Must have type 2 diabetes mellitus with inadequate glycemic control on diet and exercise.
2. Not on antihyperglycemic agent therapy (at least 12 weeks before screening) and have a screening visit fingerstick glycated hemoglobin (HbA1c) of more than or equal to 7 percent and less than or equal to 12.5 percent.
3. Have a screening visit HbA1c of more than or equal to 7.5 percent and less than or equal to 12 percent as determined by the central laboratory.
4. Must have a fasting plasma glucose of less than or equal to 300 mg/dL (16.7 mmol/L) prior to randomization.
5. Must have a fasting fingerstick glucose of greater than 120 mg/dL (6.7 mmol/L) performed at home or at the study center prior to randomization. |
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E.4 | Principal exclusion criteria |
1. History of diabetic ketoacidosis, type 1 diabetes mellitus (T1DM), pancreas or beta-cell transplantation, or diabetes secondary to pancreatitis or pancreatectomy
2. Fasting C-peptide less than 0.70 ng/mL (0.23 nmol/L) in participants for whom the investigator cannot reasonably exclude T1DM based upon clinical evaluation
3. Repeated (2 or more over a 1 week period) fasting self-monitored blood glucose measurements more than 300 mg/dL (16.7 mmol/L) prior to randomization, despite reinforcement of diet
and exercise counseling
4. History of hereditary glucose-galactose malabsorption or primary renal glucosuria
5. Has history of, or currently active, illness considered to be clinically significant by the Investigator or any other illness that the Investigator considers should exclude the patient from the study or that could interfere with the interpretation of the study results. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in glycated hemoglobin (HbA1c) from baseline to Week 26 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Day 1 (Baseline) up to Week 26 |
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E.5.2 | Secondary end point(s) |
Key secondary endpoints include :
1. Percent change in body weight from baseline to Week 26.
2. Percentage of participants with glycated hemoglobin (HbAIc) less than 7 percent at Week 26.
3. Change in systolic blood pressure from baseline to Week 26.
4. Change in high-density lipoprotein cholesterol (HDL-C) from baseline to Week 26.
5. Change in triglycerides from baseline to Week 26
6. Number of participants with adverse events
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Day 1 (Baseline) up to Week 26
2. Week 26
3. Day 1 (Baseline) up to Week 26
4. Day 1 (Baseline) up to Week 26
5. Day 1 (Baseline) up to Week 26
6. Up to 30 weeks |
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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 | No |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 5 |
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 | 32 |
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 |
Canada |
New Zealand |
Romania |
Slovakia |
Argentina |
Australia |
Brazil |
Chile |
Colombia |
Czech Republic |
Hungary |
Korea, Republic of |
Mexico |
Peru |
Russian Federation |
South Africa |
Turkey |
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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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 | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |