A Study to Investigate the Efficacy and Safety of Canagliflozin in Children and Adolescents (>=10 to <18 Years) With Type 2 Diabetes Mellitus

Study Overview
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Brief Summary
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The purpose of this study is to assess the effect of canagliflozin relative to placebo on glycated hemoglobin (HbA1c) after 26 weeks of treatment, and to assess the overall safety and tolerability of canagliflozin.

Official Title
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A Randomized, Multicenter, Double-Blind, Parallel-Group, Placebo-Controlled Study to Investigate the Efficacy and Safety of Canagliflozin in Children and Adolescents (≥10 to <18 Years) With Type 2 Diabetes Mellitus

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Canagliflozin 100 mg
* Drug: Canagliflozin 300 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants with a diagnosis of type 2 diabetes mellitus (T2DM) Random C-peptide at screening greater than (>)0.6 nanogram/milliliter (ng/mL) (>0.2 nanomole/liter [nmol]/L]) HbA1c of greater than or equal to (>=)6.5 percent (%) to less than or equal to (<=)11.0% and meets 1 of the inclusion criteria below: On diet and exercise only for at least 4 weeks prior to screening On diet and exercise and a stable dose of metformin monotherapy >=1,000 mg per day or MTD per day for at least 8 weeks prior to screening On diet and exercise and a stable insulin monotherapy regimen for at least 8 weeks prior to screening (stable dose is defined as no change in the insulin regimen [that is, type{s} of insulin] and <=15% change in the total daily dose of insulin [averaged over 1 week to account for day to day variability]) On diet and exercise and a stable combination therapy with metformin and insulin for at least 8 weeks prior to screening Exclusion Criteria: History of diabetic ketoacidosis (DKA), type 1 diabetes mellitus (T1DM), pancreas or cell transplantation, or diabetes secondary to pancreatitis or pancreatectomy or maturity onset diabetes of the young (MODY) Participants on any antihyperglycemic agents (AHAs) other than metformin, or injectable insulin within 8 weeks of the first dose of study drug (that is Day 1) Repeated (2 or more over a 1-week period) fasting self-monitoring of blood glucose (SMBG) measurements >270 milligram/deciliter (mg/dL) (>15 millimole/liter [mmol/L]) during the pretreatment phase, despite reinforcement of diet and exercise counseling Severe hypoglycemia within 6 months prior to Day 1 History of hereditary glucose-galactose malabsorption or primary renal glucosuria Alanine aminotransferase level >5.0 times the upper limit of normal (ULN) or total bilirubin >1.5 times the ULN at screening (for elevations in bilirubin: if, in the opinion of the investigator and agreed upon by the sponsor's medical officer, the elevation in bilirubin is consistent with Gilbert's disease, the subject may participate)

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single-blind run-in Period: Placebo<br>Participants will receive 1 placebo tablet matching canagliflozin 100 milligram (mg) once-daily during the 2-week single-blind placebo run-in period. | Drug: Placebo<br>* Matching placebo tablet will be administered orally once-daily.<br>|
| Experimental: Double-blind Treatment Phase: Canagliflozin or Placebo<br>Canagliflozin 100 mg/matching placebo once-daily during first 12 weeks. At Week 13, participants who have glycated hemoglobin (HbA1c) of greater than or equal to (>=)7.0 percent (%), estimated glomerular filtration rate (eGFR) >=60 milliliter/minute/1.73 meter square (mL/min/1.73 m^2) will be re-randomized to either remain on canagliflozin 100 mg/matching placebo or up-titrate to canagliflozin 300 mg/matching placebo till Week 52. | Drug: Canagliflozin 100 mg<br>* Canagliflozin 100 mg tablet will be administered orally (by mouth) once-daily.<br>* Other names: JNJ-28431754;Drug: Canagliflozin 300 mg<br>* Canagliflozin 300 mg tablet will be administered orally once-daily.<br>* Other names: JNJ-28431754;Drug: Placebo<br>* Matching placebo tablet will be administered orally once-daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Glycated Hemoglobin (HbA1c) From Baseline at Week 26 | Change from baseline in HbA1c at Week 26 will be analyzed using a pattern mixture model with multiple imputation. | Baseline, up to Week 26 | 
| Percentage of Participants with Adverse Events as a Measure of Safety and Tolerability | An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention and can therefore be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with use of a medicinal product, whether or not related to that medicinal product. | Up to Week 56 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Fasting Plasma Glucose (FPG) From Baseline at Week 26 and Week 52 | Change from baseline in FPG at Week 26 and Week 52 will be assessed. | Baseline (Day 1), Week 26, and Week 52 | 
| Change in Glycated Hemoglobin (HbA1c) From Baseline at Week 52 | Change from baseline in HbA1c at Week 52 will be analyzed using a pattern mixture model with multiple imputation. | Baseline, up to Week 52 | 
| Proportion of Participants With HbA1c less than (<)7.5 percent (%) at Week 26 and Week 52 | The proportion of participants achieving HbAIc <7.5% at Week 26 and Week 52 will be assessed. | Week 26 and Week 52 | 
| Proportion of Participants With HbA1c <7.0% at Week 26 and Week 52 | The proportion of participants achieving HbAIc <7% at Week 26 and Week 52 will be assessed. | Week 26 and Week 52 | 
| Proportion of Participants With HbA1c <6.5% at Week 26 and Week 52 | The proportion of participants achieving HbAIc <6.5% at Week 26 and Week 52 will be assessed. | Week 26 and Week 52 | 
| Time to Rescue Therapy | Time from baseline to initiation of glycemic rescue therapy for participants not responding to treatment. | Baseline (Day 1) up to Week 26 and Week 52 | 
| Proportion of Participants who will Receive Rescue Therapy | Proportion of participants receiving rescue therapy will be assessed. | Week 26 and Week 52 | 
| Percent Change in Body Weight From Baseline at Week 26 and Week 52 | The percent change in body weight from Baseline to Week 26 and Week 52 will be assessed. | Baseline (Day 1), Week 26 and Week 52 |