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

Phase 3

Completed

Conditions: Diabetes Mellitus, Type 2

Interventions: Drug: Canagliflozin 100 mg
Drug: Canagliflozin 300 mg
Drug: Placebo

Registration Number: NCT03170518

Lead Sponsor: Janssen Research & Development, LLC

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 171

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:
1. On diet and exercise only for at least 4 weeks prior to screening
2. 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
3. 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])
4. 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)

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Double-blind Treatment Phase: Canagliflozin or Placebo	Placebo	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.
Double-blind Treatment Phase: Canagliflozin or Placebo	Canagliflozin 300 mg	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.
Single-blind run-in Period: Placebo	Placebo	Participants will receive 1 placebo tablet matching canagliflozin 100 milligram (mg) once-daily during the 2-week single-blind placebo run-in period.
Double-blind Treatment Phase: Canagliflozin or Placebo	Canagliflozin 100 mg	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.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 26	Baseline (Day 1) and Week 26	Change from baseline in HbA1c at Week 26 was analyzed using a pattern mixture model with multiple imputation. Data for this outcome measure was planned to be collected and analyzed for the combined population of arm Canagliflozin 100 mg and Canagliflozin 300 mg.
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)	Baseline (Day 1) up to 30 days post last dose at Week 52 (up to Week 56)	An AE was any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non investigational) product. An AE did not necessarily have a causal relationship with the pharmaceutical/biological agent under study. TEAE was defined as the AEs occurring after first administration of double blind study intervention up to 30 days post last dose of study intervention.

Secondary Outcome Measures

Name	Time	Method
Urinary Albumin/Creatinine Ratio (ACR) at Weeks 26 and 52	Weeks 26 and 52	Urinary ACR at Weeks 26 and 52 was reported.
Change From Baseline in Fasting Plasma Glucose (FPG) at Weeks 26 and 52	Baseline (Day 1), Weeks 26 and 52	Change from baseline in FPG at Weeks 26 and Week 52 was reported. Data for this outcome measure was planned to be collected and analyzed for the combined population of arm Canagliflozin 100 mg and Canagliflozin 300 mg.
Percentage of Participants With HbA1c Less Than (<)7.5 Percent (%), <7%, and <6.5% at Weeks 26 and 52	Weeks 26 and 52	The percentage of participants with HbA1c \<7.5%, \<7.0%, and \<6.0% at Weeks 26 and 52 was reported. Data for this outcome measure was planned to be collected and analyzed for the combined population of arm Canagliflozin 100 mg and Canagliflozin 300 mg.
Percentage of Participants Who Received Rescue Therapy	Baseline (Day 1) up to Week 52	Percentage of participants who received rescue therapy was reported. Participants who met glycemic rescue criteria that is with baseline HbA1c less than (\<) 9.0 percent (%) and greater than (\>) 0.8% change from baseline in HbA1c or with baseline HbA1c \>=9% and \>0.5% change from baseline in HbA1c received the glycemic rescue therapy. Data for this outcome measure was planned to be collected and analyzed for the combined population of arm Canagliflozin 100 mg and Canagliflozin 300 mg.
Time to Rescue Therapy	Baseline (Day 1) up to Week 52	Time to rescue therapy was planned to be reported. Participants who met glycemic rescue criteria that is with baseline HbA1c less than (\<) 9.0 percent (%) and greater than (\>) 0.8% change from baseline in HbA1c or with baseline HbA1c greater than or equal to (\>=)9% and \>0.5% change from baseline in HbA1c received the glycemic rescue therapy. Data for this outcome measure was planned to be collected and analyzed for the combined population of arm Canagliflozin 100 mg and Canagliflozin 300 mg.
Percent Change From Baseline in Body Weight at Weeks 26 and 52	Baseline (Day 1), Weeks 26 and 52	The percent change from baseline in body weight at Weeks 26 and 52 was reported. Data for this outcome measure was planned to be collected and analyzed for the combined population of arm Canagliflozin 100 mg and Canagliflozin 300 mg.
Change From Baseline in Body Mass Index (BMI) at Weeks 26 and 52	Baseline (Day 1), Weeks 26, and 52	Change from baseline in BMI at Weeks 26 and 52 was reported. Data for this outcome measure was planned to be collected and analyzed for the combined population of arm Canagliflozin 100 mg and Canagliflozin 300 mg.
Percent Change From Baseline in Fasting Plasma Lipids Levels at Weeks 26 and 52	Baseline (Day 1), Weeks 26, and 52	The percentage change from baseline in fasting plasma lipids (low-density lipoprotein-cholesterol \[LDL-C\], high-density lipoprotein-cholesterol \[HDL-C\], total cholesterol, non-HDL-C, and triglycerides) at Weeks 26 and 52 was reported. Data for this outcome measure was planned to be collected and analyzed for the combined population of arm Canagliflozin 100 mg and Canagliflozin 300 mg.
Percent Change From Baseline in LDL-C to HDL-C Ratio and Non-HDL-C to LDL-C Ratio at Weeks 26 and 52	Baseline (Day 1), Weeks 26, and 52	The percentage change from baseline in LDL-C to HDL-C ratio and non-HDL-C to LDL-C ratio at Weeks 26 and 52 was reported. Data for this outcome measure was planned to be collected and analyzed for the combined population of arm Canagliflozin 100 mg and Canagliflozin 300 mg.
Change From Baseline in Systolic Blood Pressure at Weeks 26 and 52	Baseline (Day 1), Weeks 26 and 52	Change from baseline in systolic blood pressure at Weeks 26 and 52 was reported. Data for this outcome measure was planned to be collected and analyzed for the combined population of arm Canagliflozin 100 mg and Canagliflozin 300 mg.
Change From Baseline in Diastolic Blood Pressure at Weeks 26 and 52	Baseline (Day 1), Weeks 26, and 52	Change from baseline in diastolic blood pressure at Weeks 26 and 52 was reported. Data for this outcome measure was planned to be collected and analyzed for the combined population of arm Canagliflozin 100 mg and Canagliflozin 300 mg.
Change From Baseline in HbA1c at Weeks 12 and 52	Baseline (Day 1), Weeks 12, and 52	Change from baseline in HbA1c at Weeks 12 and 52 was reported. Data for this outcome measure was planned to be collected and analyzed for the combined population of arm Canagliflozin 100 mg and Canagliflozin 300 mg.
Growth Velocity at Weeks 26 and 52	Baseline (Day 1) and Weeks 26 and 52	Growth velocity (increase in height per year) at Weeks 26 and 52 was reported. Growth velocity was derived from height measurements taken at baseline (Day 1), Week 26 and Week 52 visit. Growth velocity at Week 26 was derived as: (height at Week 26 - height at baseline)/(time from baseline to week 26. Similarly, growth velocity at Week 56 was derived.
Number of Participants With Changes in Tanner Staging (Females) From Baseline at Weeks 26 and 52	Baseline (Day 1), Weeks 26, and 52	Tanner pubertal staging was assessed in female (F) for pubic hair growth and for breast development in stages (S) 1 to 5. If a participant had reached tanner S 5, no further Tanner pubertal S assessments were to be completed and reported as 'not done (ND)'. Tanner S Pubic hair growth: Pubic hair (1: No hair, 2: Downy hair, 3: More coarse and curly hair, 4: Adult-like hair quality; 5: Hair extends to medial surface of the thighs); Breast development: (1: The nipple is raised a little in this stage. The rest of the breast is still flat, 2: Breast bud forms,3: More elevated, outside areola, 4: Increased breast size, 5: Final adult-size breasts). Categories with at least 1 non-zero data values are reported. Baseline=B, Week=W.
Number of Participants With Changes in Tanner Staging (Males) From Baseline at Weeks 26 and 52	Baseline (Day 1), Weeks 26, and 52	Tanner pubertal staging was assessed in male (M) for pubic hair growth and for genitalia development in S 1 to 5. If a participant had reached Tanner S5, no further Tanner pubertal S assessments were to be completed and reported as ND. Tanner S pubic hair growth: Pubic hair (1: No hair, 2: little soft, long, lightly curled hair at penis 3: More coarse and curly hair covered larger area, 4: Adult-like hair quality; 5: Hair extends to medial surface of the thighs); Genitalia development: (1: Testes, scrotum, and penis about same size, 2: Enlargement of scrotum, testes, and penis, 3: Enlargement of penis, 4: The penis and glans became larger, 5: Genitalia size and shape same an adult male). Categories with at least 1 non-zero data values are reported. GD: genitalia development.
Change From Baseline in Bone Turnover Marker: Serum Osteocalcin and Serum Collagen Type 1 Carboxy-Telopeptide (CTx) at Weeks 26 and 52	Baseline (Day 1), Weeks 26 and 52	Change from baseline in bone turnover marker: serum osteocalcin and CTx at Weeks 26 and 52 was reported.

Trial Locations

Locations (106): Arkansas Childrens Hospital
🇺🇸
Little Rock, Arkansas, United States
Center of Excellence for Diabetes and Endocrinology (CEDE)
🇺🇸
Sacramento, California, United States
American Institute of Research
🇺🇸
Whittier, California, United States
University of Colorado School of Medicine/Children's Hospital Colorado
🇺🇸
Aurora, Colorado, United States
Nemours DuPont Hospital for Children
🇺🇸
Wilmington, Delaware, United States
TOPAZ Clinical Research
🇺🇸
Apopka, Florida, United States
Columbus Clinical Services LLC
🇺🇸
Miami, Florida, United States
Medical Research Center of Miami II Inc
🇺🇸
Miami, Florida, United States
Nicklaus Children's Hospital
🇺🇸
Miami, Florida, United States
Nemours Children's Hospital/Endocrinology
🇺🇸
Orlando, Florida, United States
Scroll for more (96 remaining)
Arkansas Childrens Hospital
🇺🇸Little Rock, Arkansas, United States