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

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03170518
• Other study ID #: CR108298
• Secondary ID: 2016-005223-8828
• Status: Completed
• Phase: Phase 3
• Start date: July 21, 2017
• Est. completion date: September 20, 2023

Study information

• Verified date: November 2023
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 171
• Est. completion date: September 20, 2023
• Est. primary completion date: September 20, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 10 Years to 17 Years

Eligibility

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)

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• Canagliflozin 100 mg
Canagliflozin 100 mg tablet will be administered orally (by mouth) once-daily.
• Canagliflozin 300 mg
Canagliflozin 300 mg tablet will be administered orally once-daily.
• Placebo
Matching placebo tablet will be administered orally once-daily.

Locations

Country	Name	City	State
Brazil	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	Instituto da Criança com Diabetes do Rio Grande do Sul - ICDRS	Porto Alegre
Brazil	Núcleo de Pesquisa Clinica	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
China	Capital Institute of Pediatrics	Beijing
China	Xiangya Hospital, Central South University	Changsha
China	The Children's Hospital, Zhejiang University School Of Medicine	Hangzhou
China	Jiangxi Provincial Children's Hospital	Nanchang
China	Jiangsu Province Hospital	Nanjing
China	Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology	Wuhan
China	Wuhan Union Hospital	Wuhan
China	Chidren's Hospital of Zhengzhou	Zheng Zhou
Greece	Athens Medical Center	Athens
Greece	General Children's Hospital 'P. and A. Kyriakou'	Athens
India	Diacon Hospital	Bangalore
India	Post Graduate Institute of Medical Education & Research (PGIMER)	Chandigarh
India	Kovai Diabetes Specialty Centre & Hospital	Coimbatore
India	Thumbay Hospital New life / Endocrinology	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
Malaysia	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
Mexico	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
Philippines	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
Poland	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	Wroclaw
Poland	Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu	Wroclaw
Russian Federation	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	Saint-Petersburg State Pediatric Medical Academy of RosZdrav, Clinical Diagnostic Center	Saint-Petersburg
Russian Federation	SBHI Children's City Multi-Profile Clinical Center named after K. A. Rauhfus	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
United States	Appalachian Clinical Research	Adairsville	Georgia
United States	University of New Mexico	Albuquerque	New Mexico
United States	TOPAZ Clinical Research	Apopka	Florida
United States	University of Colorado School of Medicine/Children's Hospital Colorado	Aurora	Colorado
United States	Avant Research Associates, LLC	Austin	Texas
United States	AM Diabetes & Endocrinology Center	Bartlett	Tennessee
United States	Floating Hospital For Children at Tufts Medical Center	Boston	Massachusetts
United States	SUNY Downstate Medical Center	Brooklyn	New York
United States	Capital Diabetes and Endocrine Associates	Camp Springs	Maryland
United States	Carolinas Research Center, LLC	Charlotte	North Carolina
United States	Cleveland Clinic Center for Pediatric Endocrinology	Cleveland	Ohio
United States	Buckeye Health and Research, LLC	Columbus	Ohio
United States	Endocrine Consultants Research	Columbus	Georgia
United States	Driscoll Children's Hospital	Corpus Christi	Texas
United States	Alas Viable Research	Henderson	Nevada
United States	Amir Ali Hassan, MD, PA	Houston	Texas
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	Sante Clinical Research	Kerrville	Texas
United States	Arkansas Childrens Hospital	Little Rock	Arkansas
United States	Texas Institute for Kidney and Endocrine Disorders	Lufkin	Texas
United States	LifeDoc Research, PLLC	Memphis	Tennessee
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	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Nemours Children's Hospital/Endocrinology	Orlando	Florida
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	WakeMed Clinical Research Institute	Raleigh	North Carolina
United States	Center of Excellence for Diabetes and Endocrinology (CEDE)	Sacramento	California
United States	Johns Hopkins All Children's Hospital	Saint Petersburg	Florida
United States	Sun Research Institute	San Antonio	Texas
United States	Asclepes Research	Spring Hill	Florida
United States	MultiCare Health System	Tacoma	Washington
United States	American Institute of Research	Whittier	California
United States	Nemours DuPont Hospital for Children	Wilmington	Delaware
United States	PMG Research of Wilmington, LLC	Wilmington	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Brazil,  China,  Greece,  India,  Malaysia,  Mexico,  Philippines,  Poland,  Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Proportion of Participants who will Receive Rescue Therapy	Proportion of participants receiving rescue therapy will be assessed.	Week 26 and Week 52
Secondary	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