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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
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
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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)
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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Double-blind Treatment Phase: Canagliflozin or PlaceboPlaceboCanagliflozin 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 PlaceboCanagliflozin 300 mgCanagliflozin 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: PlaceboPlaceboParticipants 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 PlaceboCanagliflozin 100 mgCanagliflozin 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
NameTimeMethod
Change in Glycated Hemoglobin (HbA1c) From Baseline at Week 26Baseline, up to Week 26

Change from baseline in HbA1c at Week 26 will be analyzed using a pattern mixture model with multiple imputation.

Percentage of Participants with Adverse Events as a Measure of Safety and TolerabilityUp to Week 56

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.

Secondary Outcome Measures
NameTimeMethod
Change in Fasting Plasma Glucose (FPG) From Baseline at Week 26 and Week 52Baseline (Day 1), Week 26, and Week 52

Change from baseline in FPG at Week 26 and Week 52 will be assessed.

Proportion of Participants With HbA1c <6.5% at Week 26 and Week 52Week 26 and Week 52

The proportion of participants achieving HbAIc \<6.5% at Week 26 and Week 52 will be assessed.

Proportion of Participants who will Receive Rescue TherapyWeek 26 and Week 52

Proportion of participants receiving rescue therapy will be assessed.

Percent Change in Body Weight From Baseline at Week 26 and Week 52Baseline (Day 1), Week 26 and Week 52

The percent change in body weight from Baseline to Week 26 and Week 52 will be assessed.

Change in Glycated Hemoglobin (HbA1c) From Baseline at Week 52Baseline, up to Week 52

Change from baseline in HbA1c at Week 52 will be analyzed using a pattern mixture model with multiple imputation.

Proportion of Participants With HbA1c less than (<)7.5 percent (%) at Week 26 and Week 52Week 26 and Week 52

The proportion of participants achieving HbAIc \<7.5% at Week 26 and Week 52 will be assessed.

Time to Rescue TherapyBaseline (Day 1) up to Week 26 and Week 52

Time from baseline to initiation of glycemic rescue therapy for participants not responding to treatment.

Proportion of Participants With HbA1c <7.0% at Week 26 and Week 52Week 26 and Week 52

The proportion of participants achieving HbAIc \<7% at Week 26 and Week 52 will be assessed.

Trial Locations

Locations (106)

Tongji Hospital Tongji Medical College of Huazhong University of Science and Technology

🇨🇳

Wuhan, China

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

Johns Hopkins All Children's Hospital

🇺🇸

Saint Petersburg, Florida, United States

Asclepes Research

🇺🇸

Spring Hill, Florida, United States

Appalachian Clinical Research

🇺🇸

Adairsville, Georgia, United States

Endocrine Consultants Research

🇺🇸

Columbus, Georgia, United States

University of Iowa Hospitals and Clinics

🇺🇸

Iowa City, Iowa, United States

Capital Diabetes and Endocrine Associates

🇺🇸

Camp Springs, Maryland, United States

Floating Hospital For Children at Tufts Medical Center

🇺🇸

Boston, Massachusetts, United States

Alas Viable Research

🇺🇸

Henderson, Nevada, United States

University of New Mexico

🇺🇸

Albuquerque, New Mexico, United States

SUNY Downstate Medical Center

🇺🇸

Brooklyn, New York, United States

Icahn School of Medicine at Mount Sinai

🇺🇸

New York, New York, United States

Carolinas Research Center, LLC

🇺🇸

Charlotte, North Carolina, United States

WakeMed Clinical Research Institute

🇺🇸

Raleigh, North Carolina, United States

PMG Research of Wilmington, LLC

🇺🇸

Wilmington, North Carolina, United States

Cleveland Clinic Center for Pediatric Endocrinology

🇺🇸

Cleveland, Ohio, United States

Buckeye Health and Research, LLC

🇺🇸

Columbus, Ohio, United States

Children's Hospital of Philadelphia

🇺🇸

Philadelphia, Pennsylvania, United States

AM Diabetes & Endocrinology Center

🇺🇸

Bartlett, Tennessee, United States

LifeDoc Research, PLLC

🇺🇸

Memphis, Tennessee, United States

Avant Research Associates, LLC

🇺🇸

Austin, Texas, United States

Driscoll Children's Hospital

🇺🇸

Corpus Christi, Texas, United States

Amir Ali Hassan, MD, PA

🇺🇸

Houston, Texas, United States

Sante Clinical Research

🇺🇸

Kerrville, Texas, United States

Texas Institute for Kidney and Endocrine Disorders

🇺🇸

Lufkin, Texas, United States

Sun Research Institute

🇺🇸

San Antonio, Texas, United States

MultiCare Health System

🇺🇸

Tacoma, Washington, United States

Hospital Universitario Joao de Barros Barreto - UFPA

🇧🇷

Belem, Brazil

Santa Casa de Misericordia de Belo Horizonte

🇧🇷

Belo Horizonte, Brazil

Condominio Centro Clinico do Lago

🇧🇷

Brasilia, Brazil

Centro de Diabetes Curitiba Ltda

🇧🇷

Curitiba, Brazil

Núcleo de Pesquisa Clinica

🇧🇷

Porto Alegre, Brazil

Instituto da Criança com Diabetes do Rio Grande do Sul - ICDRS

🇧🇷

Porto Alegre, Brazil

Ruschel Medicina e Pesquisa Clínica Ltda

🇧🇷

Rio de Janeiro, Brazil

Hospital e Maternidade Dr Christovao da Gama S.A

🇧🇷

Santo Andre, Brazil

Hospital Das Clinicas Da Faculdade De Medicina Da USP

🇧🇷

Sao Paulo, Brazil

IPEC - Instituto de Pesquisa Clínica Ltda

🇧🇷

São Paulo, Brazil

Santa Casa de Misericórdia de Votuporanga

🇧🇷

Votuporanga, Brazil

Capital Institute of Pediatrics

🇨🇳

Beijing, China

Xiangya Hospital Central South University

🇨🇳

Changsha, China

The Childrens Hospital Zhejiang University School Of Medicine

🇨🇳

Hangzhou, China

Jiangxi Provincial Children's Hospital

🇨🇳

Nanchang, China

Jiangsu Province Hospital

🇨🇳

Nanjing, China

Wuhan Union Hospital

🇨🇳

Wuhan, China

Chidren's Hospital of Zhengzhou

🇨🇳

Zheng Zhou, China

General Children's Hospital 'P. and A. Kyriakou'

🇬🇷

Athens, Greece

Athens Medical Center

🇬🇷

Athens, Greece

Diacon Hospital

🇮🇳

Bangalore, India

Post Graduate Institute of Medical Education And Research PGIMER

🇮🇳

Chandigarh, India

Kovai Diabetes Specialty Centre & Hospital

🇮🇳

Coimbatore, India

Quality Care India Limited

🇮🇳

Hyderabad, India

P D Hinduja National Hospital and Medical Research Center

🇮🇳

Mumbai, India

Sir Ganga Ram Hospital

🇮🇳

New Delhi, India

Jehangir Clinical Development Center Pvt Ltd

🇮🇳

Pune, India

Jothydev's Diabetes Research Centre

🇮🇳

Trivandrum, India

Hospital Sultanah Bahiyah

🇲🇾

Alor Setar, Malaysia

Hospital Pulau Pinang

🇲🇾

George Town, Malaysia

Hospital Raja Permaisuri Bainun

🇲🇾

Ipoh, Malaysia

Hospital Tuanku Fauziah

🇲🇾

Kangar, Malaysia

Hospital University Sains Malaysia

🇲🇾

Kubang Kerian, Malaysia

Investigación Biomédica para el Desarrollo de Fármacos S.A. de C.V.

🇲🇽

Aguascalientes, Mexico

Bio Investigación AMARC, S.C.

🇲🇽

Ciudad de Mexico, Mexico

Instituto Nacional de Pediatría

🇲🇽

Coyoacan, Mexico

Desarrollo Ético en Investigación Clínica S.C .

🇲🇽

Guadalajara, Mexico

Centro de Estudios de Investigación Metabólicos y Cardiovasculares S.C.

🇲🇽

Madero, Mexico

St Lucas Clinical Research Center

🇲🇽

Merida, Mexico

UBAM Unidad Biomédica Avanzada Monterrey

🇲🇽

Monterrey, Mexico

Consultorio Medico

🇲🇽

Puebla, Mexico

Centro Integral Medico SJR, SC

🇲🇽

San Juan del Rio, Mexico

Centro De Investigacion Medica De Occidente, S.C.

🇲🇽

Zapopan, Mexico

Chong Hua Hospital

🇵🇭

Cebu City, Philippines

Norzel MedicaL and Diagnostic Clinic

🇵🇭

Cebu City, Philippines

De La Salle Health Sciences Institute- DLSUMC

🇵🇭

Dasmarinas, Philippines

Davao Doctors Hospital

🇵🇭

Davao City, Philippines

Docbebet Diabetes Clinic

🇵🇭

San Fernando City, Philippines

Gornoslaskie Centrum Zdrowia, SPSK nr 6 Slaskiego Uniwersytetu Medycznego w Katowicach

🇵🇱

Katowice, Poland

WSS Dzieciecy prof.dr S.Popowskiego w Olsztynie,Od.Pediatryczny VI Reumatologiczno-Endokrynologiczny

🇵🇱

Olsztyn, Poland

Gabinet Pediatryczny Artur Mazur

🇵🇱

Rzeszów, Poland

Instytut 'Pomnik-Centrum Zdrowia Dziecka', Klinika Endokrynologii i Diabetologii

🇵🇱

Warszawa, Poland

Specjalistyczna Praktyka Lekarska Aspiro

🇵🇱

Wrocław, Poland

Uniwersytecki Szpital Kliniczny im Jana Mikulicza Radeckiego we Wroclawiu

🇵🇱

Wrocław, Poland

Regional Pediatric Clinical Hospital No.1

🇷🇺

Ekaterinburg, Russian Federation

Republic Children Clinical Hospital of the Ministry of Health of Udmurtskaya Republic

🇷🇺

Izhevsk, Russian Federation

Kirov Clinical Hospital #7 named after V.I. Yurlova

🇷🇺

Kirov, Russian Federation

Krasnoyarsk State Medical University

🇷🇺

Krasnoyarsk, Russian Federation

Natiolal Medical Research Center of Endocrinology

🇷🇺

Moscow, Russian Federation

Russian National Research Medical University named after N.I.Pirogov

🇷🇺

Moscow, Russian Federation

Children City Clinical Hospital #1

🇷🇺

Novosibirsk, Russian Federation

Omsk Regional Childrens Clinical Hospital

🇷🇺

Omsk, Russian Federation

City Children Clinical Outpatient Clinic #5

🇷🇺

Perm, Russian Federation

SBHI Children's City Multi-Profile Clinical Center named after K. A. Rauhfus

🇷🇺

Saint-Petersburg, Russian Federation

Saint-Petersburg State Pediatric Medical Academy of RosZdrav, Clinical Diagnostic Center

🇷🇺

Saint-Petersburg, Russian Federation

Samara Regional Children Clinical Hospital named after N.N. Ivanova

🇷🇺

Samara, Russian Federation

Children Outpatient Clinic 45 Of Nevskiy Region

🇷🇺

St. Petersburg, Russian Federation

Siberian State Medical University

🇷🇺

Tomsk, Russian Federation

Tver Regional Clinical Hospital

🇷🇺

Tver, Russian Federation

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