A Study to Investigate the Efficacy and Safety of Canagliflozin in Children and Adolescents (>=10 to <18 Years) With Type 2 Diabetes Mellitus
- 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
-
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:
- On diet and exercise only for at least 4 weeks prior to screening
- 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
- 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])
- On diet and exercise and a stable combination therapy with metformin and insulin for at least 8 weeks prior to screening
- 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 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.
Urinary Albumin/Creatinine Ratio (ACR) at Weeks 26 and 52 Weeks 26 and 52 Urinary ACR at Weeks 26 and 52 was reported.
Trial Locations
- Locations (106)
Buckeye Health and Research, LLC
🇺🇸Columbus, Ohio, United States
Sante Clinical Research
🇺🇸Kerrville, Texas, United States
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
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
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
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
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
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
Tongji Hospital Tongji Medical College of Huazhong University of Science and Technology
🇨🇳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
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
🇵🇱Rzeszow, Poland
Instytut 'Pomnik-Centrum Zdrowia Dziecka', Klinika Endokrynologii i Diabetologii
🇵🇱Warszawa, Poland
Uniwersytecki Szpital Kliniczny im Jana Mikulicza Radeckiego we Wroclawiu
🇵🇱Wroclaw, Poland
Specjalistyczna Praktyka Lekarska Aspiro
🇵🇱Wroclaw, 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