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

Janssen Research & Development, LLC171 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

171

Conditions

Diabetes Mellitus, Type 2

Interventions

Canagliflozin 100 mgDRUG

Canagliflozin 100 mg tablet will be administered orally (by mouth) once-daily.

Canagliflozin 300 mgDRUG

Canagliflozin 300 mg tablet will be administered orally once-daily.

PlaceboDRUG

Matching placebo tablet will be administered orally once-daily.

Eligibility

Sex: ALLMin age: 10 YearsMax age: 17 Years

Medical Language ↔ Plain English

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)

Locations (106)

Outcomes

Primary Outcomes

Change From Baseline in Glycated Hemoglobin (HbA1c) at 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.

Time frame: Baseline (Day 1) and Week 26

Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)

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.

Time frame: Baseline (Day 1) up to 30 days post last dose at Week 52 (up to Week 56)

Secondary Outcomes

Change From Baseline in Fasting Plasma Glucose (FPG) at 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.

Time frame: Baseline (Day 1), Weeks 26 and 52

Percentage of Participants With HbA1c Less Than (<)7.5 Percent (%), <7%, and <6.5% at 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.

Time frame: Weeks 26 and 52

Percentage of Participants Who Received Rescue Therapy

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.

Data from ClinicalTrials.gov

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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

...and 96 more locations

Time frame: Baseline (Day 1) up to Week 52

Time to Rescue Therapy

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.

Time frame: Baseline (Day 1) up to Week 52

Percent Change From Baseline in Body Weight at 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.

Time frame: Baseline (Day 1), Weeks 26 and 52

Change From Baseline in Body Mass Index (BMI) at 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.

Time frame: Baseline (Day 1), Weeks 26, and 52

Percent Change From Baseline in Fasting Plasma Lipids Levels at 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.

Time frame: Baseline (Day 1), Weeks 26, and 52

Percent Change From Baseline in LDL-C to HDL-C Ratio and Non-HDL-C to LDL-C Ratio at 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.

Time frame: Baseline (Day 1), Weeks 26, and 52

Change From Baseline in Systolic Blood Pressure at 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.

Time frame: Baseline (Day 1), Weeks 26 and 52

Change From Baseline in Diastolic Blood Pressure at 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.

Time frame: Baseline (Day 1), Weeks 26, and 52

Change From Baseline in HbA1c at 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.

Time frame: Baseline (Day 1), Weeks 12, and 52

Growth Velocity at 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.

Time frame: Baseline (Day 1) and Weeks 26 and 52

Number of Participants With Changes in Tanner Staging (Females) From Baseline at 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.

Time frame: Baseline (Day 1), Weeks 26, and 52

Number of Participants With Changes in Tanner Staging (Males) From Baseline at 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.

Time frame: Baseline (Day 1), Weeks 26, and 52

Change From Baseline in Bone Turnover Marker: Serum Osteocalcin and Serum Collagen Type 1 Carboxy-Telopeptide (CTx) at Weeks 26 and 52

Change from baseline in bone turnover marker: serum osteocalcin and CTx at Weeks 26 and 52 was reported.

Time frame: Baseline (Day 1), Weeks 26 and 52

Urinary Albumin/Creatinine Ratio (ACR) at Weeks 26 and 52

Urinary ACR at Weeks 26 and 52 was reported.

Time frame: Weeks 26 and 52