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

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

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 Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Placebo; Drug: Canagliflozin 100 mg; Drug: Canagliflozin 300 mg

• Study Type: Interventional
• Enrollment (Actual): 171
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • Belem, Brazil, 66073-000
    • Hospital Universitário João de Barros Barreto - UFPA
  • Belo Horizonte, Brazil, 30150-221
    • Santa Casa de Misericordia de Belo Horizonte
  • Brasilia, Brazil, 71625-009
    • Condominio Centro Clinico do Lago
  • Curitiba, Brazil, 80810-040
    • Centro de Diabetes Curitiba Ltda
  • Porto Alegre, Brazil, 90430-001
    • Nucleo De Pesquisa Clinica
  • Porto Alegre, Brazil, 91350-250
    • Instituto da Criança com Diabetes do Rio Grande do Sul - ICDRS
  • Rio de Janeiro, Brazil, 22270-060
    • Ruschel Medicina e Pesquisa Clínica Ltda
  • Santo Andre, Brazil, 09030-010
    • Hospital e Maternidade Dr Christovao da Gama S.A
  • Sao Paulo, Brazil, 05403-000
    • Hospital Das Clinicas Da Faculdade De Medicina Da USP
  • São Paulo, Brazil, 01223-001
    • IPEC - Instituto de Pesquisa Clínica Ltda
  • Votuporanga, Brazil, 15500-003
    • Santa Casa de Misericórdia de Votuporanga
• China
  • Beijing, China, 100000
    • Capital Institute of Pediatrics
  • Changsha, China, 410008
    • Xiangya Hospital, Central South University
  • Hangzhou, China, 310052
    • The Children's Hospital, Zhejiang University school of medicine
  • Nanchang, China, 330006
    • Jiangxi Provincial Children's Hospital
  • Nanjing, China, 210029
    • Jiangsu Province Hospital
  • Wuhan, China, 430023
    • Wuhan Union Hospital
  • Wuhan, China, 430030
    • Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology
  • Zheng Zhou, China, 450003
    • Chidren's Hospital of Zhengzhou
• Greece
  • Athens, Greece, 11527
    • General Children's Hospital 'P. and A. Kyriakou'
  • Athens, Greece, 15125
    • Athens Medical Center
• India
  • Bangalore, India, 560010
    • Diacon Hospital
  • Chandigarh, India, 160012
    • Post Graduate Institute of Medical Education & Research (PGIMER)
  • Coimbatore, India, 641 009
    • Kovai Diabetes Specialty Centre & Hospital
  • Hyderabad, India, 500024
    • Thumbay Hospital New life / Endocrinology
  • Mumbai, India, 400016
    • P.D. Hinduja National Hospital and - Medical Research Center
  • New Delhi, India, 110060
    • Sir Ganga Ram Hospital
  • Pune, India, 411001
    • Jehangir Clinical Development Center Pvt Ltd
  • Trivandrum, India, 695032
    • Jothydev's Diabetes Research Centre
• Malaysia
  • Alor Setar, Malaysia, 5460
    • Hospital Sultanah Bahiyah
  • George Town, Malaysia, 10990
    • Hospital Pulau Pinang
  • Ipoh, Malaysia, 30990
    • Hospital Raja Permaisuri Bainun
  • Kangar, Malaysia, 1000
    • Hospital Tuanku Fauziah
  • Kubang Kerian, Malaysia, 16150
    • Hospital University Sains Malaysia
• Mexico
  • Aguascalientes, Mexico, 20010
    • Investigación Biomédica para el Desarrollo de Fármacos S.A. de C.V.
  • Ciudad de Mexico, Mexico, 11400
    • Bio Investigación AMARC, S.C.
  • Coyoacan, Mexico, 4530
    • Instituto Nacional de Pediatría
  • Guadalajara, Mexico, 44500
    • Desarrollo Ético en Investigación Clínica S.C .
  • Madero, Mexico, 89440
    • Centro de Estudios de Investigación Metabólicos y Cardiovasculares S.C.
  • Merida, Mexico, 97217
    • St Lucas Clinical Research Center
  • Monterrey, Mexico, 64460
    • UBAM Unidad Biomédica Avanzada Monterrey
  • Puebla, Mexico, 72190
    • Consultorio Médico
  • San Juan del Rio, Mexico, 76800
    • Centro Integral Medico SJR, SC
  • Zapopan, Mexico, 45116
    • Centro de Investigacion Medica de Occidente, S.C.
• Philippines
  • Cebu City, Philippines, 6000
    • Chong Hua Hospital
  • Cebu City, Philippines, 6000
    • Norzel Medical and Diagnostic Clinic
  • Dasmarinas, Philippines, 4114
    • De La Salle Health Sciences Institute- DLSUMC
  • Davao City, Philippines, 8000
    • Davao Doctors Hospital
  • San Fernando City, Philippines, 2000
    • Docbebet Diabetes Clinic
• Poland
  • Katowice, Poland, 40-752
    • Gornoslaskie Centrum Zdrowia, SPSK nr 6 Slaskiego Uniwersytetu Medycznego w Katowicach
  • Olsztyn, Poland, 10-561
    • WSS Dzieciecy prof.dr S.Popowskiego w Olsztynie,Od.Pediatryczny VI Reumatologiczno-Endokrynologiczny
  • Rzeszów, Poland, 35-301
    • Gabinet Pediatryczny Artur Mazur
  • Warszawa, Poland, 04-730
    • Instytut 'Pomnik-Centrum Zdrowia Dziecka', Klinika Endokrynologii i Diabetologii
  • Wrocław, Poland, 50-341
    • Specjalistyczna Praktyka Lekarska Aspiro
  • Wrocław, Poland, 50-368
    • Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu
• Russian Federation
  • Ekaterinburg, Russian Federation, 620149
    • Regional Pediatric Clinical Hospital No.1
  • Izhevsk, Russian Federation, 426009
    • Republic Children Clinical Hospital of the Ministry of Health of Udmurtskaya Republic
  • Kirov, Russian Federation, 610014
    • Kirov Clinical Hospital #7 named after V.I. Yurlova
  • Krasnoyarsk, Russian Federation, 660022
    • Krasnoyarsk State Medical University
  • Moscow, Russian Federation, 117036
    • Natiolal Medical Research Center of Endocrinology
  • Moscow, Russian Federation, 123317
    • Russian National Research Medical University named after N.I.Pirogov
  • Novosibirsk, Russian Federation, 630048
    • Children City Clinical Hospital #1
  • Omsk, Russian Federation, 644001
    • Omsk Regional Childrens Clinical Hospital
  • Perm, Russian Federation, 614066
    • City Children Clinical Outpatient Clinic #5
  • Saint-Petersburg, Russian Federation, 191036
    • SBHI Children's City Multi-Profile Clinical Center named after K. A. Rauhfus
  • Saint-Petersburg, Russian Federation, 194100
    • Saint-Petersburg State Pediatric Medical Academy of RosZdrav, Clinical Diagnostic Center
  • Samara, Russian Federation, 443079
    • Samara Regional Children Clinical Hospital named after N.N. Ivanova
  • St. Petersburg, Russian Federation, 193312
    • Children Outpatient Clinic 45 Of Nevskiy Region
  • Tomsk, Russian Federation, 634050
    • Siberian State Medical University
  • Tver, Russian Federation, 170100
    • Tver Regional Clinical Hospital
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Arkansas Childrens Hospital
  • California
    • Sacramento, California, United States, 95821
      • Center of Excellence for Diabetes and Endocrinology (CEDE)
    • Whittier, California, United States, 90603
      • American Institute of Research
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado School of Medicine/Children's Hospital Colorado
  • Delaware
    • Wilmington, Delaware, United States, 19803
      • Nemours DuPont Hospital for Children
  • Florida
    • Apopka, Florida, United States, 32703
      • Topaz Clinical Research
    • Miami, Florida, United States, 33155
      • Nicklaus Children's Hospital
    • Miami, Florida, United States, 33125
      • Columbus Clinical Services LLC
    • Miami, Florida, United States, 33134
      • Medical Research Center of Miami II Inc
    • Orlando, Florida, United States, 32827
      • Nemours Children's Hospital/Endocrinology
    • Saint Petersburg, Florida, United States, 33701
      • Johns Hopkins All Children's Hospital
    • Spring Hill, Florida, United States, 34609
      • Asclepes Research
  • Georgia
    • Adairsville, Georgia, United States, 30103
      • Appalachian Clinical Research
    • Columbus, Georgia, United States, 31904-4501
      • Endocrine Consultants Research
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics
  • Maryland
    • Camp Springs, Maryland, United States, 20746
      • Capital Diabetes and Endocrine Associates
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Floating Hospital For Children at Tufts Medical Center
  • Nevada
    • Henderson, Nevada, United States, 89014
      • Alas Viable Research
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • University of New Mexico
  • New York
    • Brooklyn, New York, United States, 11203
      • SUNY Downstate Medical Center
    • New York, New York, United States, 10029-6500
      • Icahn School of Medicine at Mount Sinai
  • North Carolina
    • Charlotte, North Carolina, United States, 28215
      • Carolinas Research Center, LLC
    • Raleigh, North Carolina, United States, 27610
      • WakeMed Clinical Research Institute
    • Wilmington, North Carolina, United States, 28401
      • PMG Research of Wilmington, LLC
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Center for Pediatric Endocrinology
    • Columbus, Ohio, United States, 43207
      • Buckeye Health and Research, LLC
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
  • Tennessee
    • Bartlett, Tennessee, United States, 38133-4063
      • AM Diabetes & Endocrinology Center
    • Memphis, Tennessee, United States, 38115
      • LifeDoc Research, PLLC
  • Texas
    • Austin, Texas, United States, 78709
      • Avant Research Associates, LLC
    • Corpus Christi, Texas, United States, 78411
      • Driscoll Children's Hospital
    • Houston, Texas, United States, 77089
      • Amir Ali Hassan, MD, PA
    • Kerrville, Texas, United States, 78028
      • Sante Clinical Research
    • Lufkin, Texas, United States, 75904
      • Texas Institute for Kidney and Endocrine Disorders
    • San Antonio, Texas, United States, 78215
      • Sun Research Institute
  • Washington
    • Tacoma, Washington, United States, 98405
      • MultiCare Health System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single-blind run-in Period: Placebo; 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; Matching placebo tablet will be administered orally once-daily.
Experimental: Double-blind Treatment Phase: Canagliflozin or 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.	Drug: Placebo; Matching placebo tablet will be administered orally once-daily.; Drug: Canagliflozin 100 mg; Canagliflozin 100 mg tablet will be administered orally (by mouth) once-daily.; Other Names: JNJ-28431754; Drug: Canagliflozin 300 mg; Canagliflozin 300 mg tablet will be administered orally once-daily.; Other Names: JNJ-28431754

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Body Mass Index (BMI) From Baseline at Week 26 and Week 52	Change from baseline in BMI at Week 26 and Week 52 will be assessed.	Baseline (Day 1), Week 26 and Week 52
Percent Change in Fasting Plasma Lipid Levels From Baseline at Week 26 and Week 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 Week 26 and Week 52 will be assessed.	Baseline (Day 1), Week 26 and Week 52
Percent Change in LDL-C to HDL-C Ratio and Non-HDL-C to LDL-C Ratio From Baseline at Week 26 and Week 52	The percentage change from baseline in ratio of LDL-C to HDL-C and non-HDL-C to LDL-C at Week 26 and Week 52 will be assessed.	Baseline (Day 1), Week 26 and Week 52
Change in Systolic Blood Pressure From Baseline at Week 26 and Week 52	The change in systolic blood pressure from baseline to Week 26 and week 52 will be assessed.	Baseline (Day 1), Week 26 and Week 52
Change in Diastolic Blood Pressure From Baseline at Week 26 and Week 52	The change in diastolic blood pressure from baseline to Week 26 and week 52 will be assessed.	Baseline (Day 1), Week 26 and Week 52
Change in HbA1c From Baseline at Week 12 and Week 52	Change from baseline in HbA1c at Week 12 and Week 52 will be assessed.	Baseline (Day 1), Week 12 and Week 52
Change in Growth Velocity From Baseline at Week 26 and Week 52	The change in growth velocity from baseline at Week 26 and Week 52 will be assessed.	Baseline (Day 1), Week 26 and Week 52
Change in Tanner Staging From Baseline at Week 26 and Week 52	The change in tanner staging from baseline at Week 26 and Week 52 will be assessed. A low stage (Stage I) corresponds to a pre-pubertal stage and a high stage (Stage V) to an adult stage.	Baseline (Day 1), Week 26 and Week 52
Change in Bone Turnover Marker: Serum Osteocalcin From Baseline at Week 26 and Week 52	Change from baseline in serum osteocalcin (bone turnover marker) at Week 26 and Week 52 will be assessed.	Baseline (Day 1), Week 26 and Week 52
Change in Bone Turnover Marker: Serum Collagen Type 1 Carboxy-Telopeptide (CTx) From Baseline at Week 26 and Week 52	Change from baseline in serum collagen Type 1 CTx (bone turnover marker) at Week 26 and Week 52 will be assessed.	Baseline (Day 1), Week 26 and Week 52
Change in Urinary Albumin/Creatinine Ratio (ACR) From Baseline at Week 26 and Week 52	Change from baseline in urinary ACR at Week 26 and Week 52 will be assessed.	Baseline (Day 1), Week 26 and Week 52

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC
• Investigators: Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (Actual): July 21, 2017
• Primary Completion (Actual): September 20, 2023
• Study Completion (Actual): September 20, 2023

Study Registration Dates

• First Submitted: May 26, 2017
• First Submitted That Met QC Criteria: May 26, 2017
• First Posted (Actual): May 31, 2017

Study Record Updates

• Last Update Posted (Actual): November 8, 2023
• Last Update Submitted That Met QC Criteria: November 7, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Canagliflozin
• Other Study ID Numbers: CR108298; 2016-005223-88 (EudraCT Number); 28431754DIA3018 (Other Identifier: Janssen Research & Development, LLC)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No