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 | 21.1 |
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 canagliflozin relative to placebo on HbA1c after 26 weeks of treatment. - To assess the overall 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 effect of canagliflozin relative to placebo in the subset of subjects taking background metformin (with or without insulin) on HbA1c.
After 26 weeks of treatment, to assess the effect of canagliflozin relative to placebo on: - FPG - Proportion of subjects with HbA1c <7.5%, <7.0% and <6.5% - Time to rescue therapy and proportion of subjects receiving rescue therapy - Body weight
After 52 weeks of treatment, to assess the effect of canagliflozin relative to placebo on: - HbA1c and FPG - Proportion of subjects with HbA1c <7.5%, <7.0% and <6.5% - Time to rescue therapy and proportion of subjects receiving rescue therapy - Body weight
Additional Secondary Objectives are listed in the protocol.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.) Male or female between the ages ≥ 10 to <18 years at the time of screening. 2.) Diagnosis of T2DM. 3.) Random C-peptide at screening >0.6 ng/mL (>0.2 nmol/L) 4.) Absence of pancreatic autoimmunity (GAD, and islet cell antigen 2 [IA2] antibody negative). 5.) HbA1c of ≥ 6.5% to ≤ 11.0% and meets 1 of the inclusion criteria below: a.) On diet and exercise only for at least 4 weeks prior to screening. b.) On diet and exercise and a stable dose of metformin monotherapy ≥ 1,000 mg per day or MTD per day (defined by the investigator) for at least 8 weeks prior to screening, c.) On diet and exercise and a stable insulin monotherapy regimen for at least 8 weeks prior to screening d.) On diet and exercise and a stable combination therapy with metformin and insulin for at least 8 weeks prior to screening.
Further inclusion criteria are listed in the protocol. |
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E.4 | Principal exclusion criteria |
Diabetes-Related/Metabolic 1. History of DKA, T1DM, pancreas or B-cell transplantation, or diabetes secondary to pancreatitis or pancreatectomy or maturity-onset diabetes of the young (MODY). 2. On any AHAs other than metformin, or injectable insulin within 8 weeks of the first dose of study drug (ie, Day 1). 3. Repeated (ie, 2 or more over a 1-week period) fasting SMBG glucose measurements >270 mg/dL (>15 mmol/L) during the pretreatment phase, despite reinforcement of diet and exercise counseling. 4. Severe hypoglycemia within 6 months prior to Day 1. 5. History of hereditary glucose-galactose malabsorption or primary renal glucosuria.
Renal/Cardiovascular 6. Renal disease that required treatment with immunosuppressive therapy or a history of dialysis or renal transplant.
Gastrointestinal 7. Known significant liver disease (eg, acute hepatitis, chronic active hepatitis, cirrhosis).
Further exclusion criteria are listed in the protocol. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint will be the change in HbA1c from baseline to Week 26. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Key secondary endpoints include: a) change from baseline to Week 26 in FPG, body weight, proportion of subjects with an HbA1c <7.5%, <7.0%, and <6.5%, time to rescue and proportion of subjects receiving rescue therapy. b) change from baseline to Week 52 in FPG, body weight, proportion of subjects with an HbA1c <7.5%, <7.0%, and <6.5%, time to rescue and proportion of subjects receiving rescue therapy. c) change from baseline to Week 52 of BMI, fasting lipid profile, systolic and diastolic blood pressure. d) change in HbA1c from baseline to Week 12. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
a) Week 26 b) Week 52 c) Week 26 and Week 52 d) Week 12 |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
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 | Yes |
E.8.1.7.1 | Other trial design description |
Eligible subjects may be re-randomized at Week 13 to stay on 100mg or uptitrate to 300mg or placebo |
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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 | 2 |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
Brazil |
China |
Greece |
India |
Malaysia |
Mexico |
Philippines |
Poland |
Russian Federation |
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.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 4 |