A Study of the Effects of Canagliflozin (JNJ-28431754) on Renal Endpoints in Adult Participants With Type 2 Diabetes Mellitus (CANVAS-R)

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by Janssen Research & Development, LLC
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT01989754
First received: October 17, 2013
Last updated: October 16, 2014
Last verified: October 2014
  Purpose

The purpose of this study is to assess the effect of canagliflozin compared to placebo on progression of albuminuria in participants with Type 2 Diabetes Mellitus receiving standard care but with inadequate glycemic control and at elevated risk of cardiovascular events.


Condition Intervention Phase
Diabetes Mellitus, Type 2
Albuminuria
Drug: Placebo
Drug: Canagliflozin, 100 mg
Drug: Canagliflozin, 300 mg
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Multicenter, Double-Blind, Parallel, Placebo-Controlled Study of the Effects of Canagliflozin on Renal Endpoints in Adult Subjects With Type 2 Diabetes Mellitus

Resource links provided by NLM:


Further study details as provided by Janssen Research & Development, LLC:

Primary Outcome Measures:
  • Number of participants with progression of albuminuria [ Time Frame: Baseline, Week 26, 52, 78, 104, 156 ] [ Designated as safety issue: No ]
    Progression of albuminuria is defined as the development of microalbuminuria or macroalbuminuria in a participant with baseline normoalbuminuria or the development of macroalbuminuria in a participant with baseline microalbuminuria, accompanied by an urinary albumin/creatinine ratio (ACR) value increase of greater than or equal to 30% from baseline.


Secondary Outcome Measures:
  • Number of participants with regression of albuminuria [ Time Frame: Baseline, Week 26, 52, 78, 104, 156 ] [ Designated as safety issue: No ]
    Regression of albuminuria is defined as the development of normoalbuminuria in a participant with baseline microalbuminuria or macroalbuminuria, or the development of microalbuminuria in a participant with baseline macroalbuminuria, accompanied by a decrease in the urinary ACR value of greater than or equal to 30% from baseline.

  • Change in estimated glomerular filtration rate (eGFR) from baseline to the last off-treatment measurement [ Time Frame: Baseline, up to Day 30 of post treatment follow-up ] [ Designated as safety issue: No ]
  • Urinary albumin/creatinine ratio at last on-treatment visit [ Time Frame: Baseline, Week 156 ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Major adverse cardiovascular (CV) events [ Time Frame: Baseline, up to April 2017 ] [ Designated as safety issue: Yes ]
    Cardiovascular safety data will be evaluated as the number of major adverse cardiovascular events, including CV death, nonfatal myocardial infarction (MI), and nonfatal stroke.


Estimated Enrollment: 5700
Study Start Date: January 2014
Estimated Study Completion Date: April 2017
Estimated Primary Completion Date: April 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Canagliflozin (JNJ-28431754)
Each patient will receive canagliflozin (JNJ-28431754) 100 mg once daily during the first 13 weeks, then the dose may be increased to 300 mg once daily.
Drug: Canagliflozin, 100 mg
One 100 mg capsule taken orally (by mouth) once daily
Drug: Canagliflozin, 300 mg
One 300 mg capsule taken orally (by mouth) once daily
Placebo Comparator: Placebo
Each patient will receive placebo (inactive medication) once daily.
Drug: Placebo
One placebo capsule taken orally (by mouth) once daily for 156 weeks

Detailed Description:

The study will be conducted in adult participants with Type 2 Diabetes Mellitus (T2DM), receiving standard of care for hyperglycemia and cardiovascular (CV) risk factors, who have either a history of a prior CV event or 2 or more risk factors for a CV event. Participants will be randomly assigned in a 1:1 ratio to canagliflozin or matching placebo to be taken once daily. Canagliflozin will be provided at a dose of 100 mg/day through Week 13 and then increased at the discretion of the investigator to a dose of 300 mg/day, if the participant requires additional glycemic control and is tolerating the 100 mg dose.

The study will consist of a 2-week screening period and a double-blind treatment period lasting between 78 and 156 weeks with study completion in April 2017. A total of 5,700 participants will be recruited into the study; the maximum duration of the study for each participant can be up to 3.5 years. Participants can be either drug naïve to antihyperglycemic agents, using monotherapy, or using combination of antihyperglycemic therapy for the control of blood glucose levels.

  Eligibility

Ages Eligible for Study:   30 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Must have a diagnosis of type 2 diabetes mellitus
  • Must have inadequate diabetes control (as defined by glycosylated hemoglobin level >=7.0% to <=10.5% at screening)
  • History or high risk of CV events
  • Must be either not on antihyperglycemic agents (AHA) therapy, or on AHA monotherapy, or combination AHA therapy with any approved agent for the control of blood glucose levels.

Exclusion Criteria

  • History of diabetic ketoacidosis, type 1 diabetes mellitus, pancreas or beta-cell transplantation, or diabetes secondary to pancreatitis or pancreatectomy
  • History of one or more severe hypoglycemic episode within 6 months before screening
  • History of hereditary glucose-galactose malabsorption or primary renal glucosuria
  • Ongoing, inadequately controlled thyroid disorder
  • Renal disease that required treatment with immunosuppressive therapy or a history of chronic dialysis or renal transplant
  • Myocardial infarction, unstable angina, revascularization procedure, or cerebrovascular accident within 3 months before screening.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01989754

Contacts
Contact: Use link at the bottom of the page to see if you qualify for an enrolling site (see list). If you still have questions: JNJ.CT@sylogent.com

  Show 447 Study Locations
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
  More Information

Additional Information:
No publications provided

Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT01989754     History of Changes
Other Study ID Numbers: CR102647, 2013-003050-25, 28431754DIA4003
Study First Received: October 17, 2013
Last Updated: October 16, 2014
Health Authority: United States: Food and Drug Administration
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Brazil: National Health Surveillance Agency
Mexico: Federal Commission for Protection Against Health Risks
Canada: Health Canada
Czech Republic: State Institute for Drug Control
Hungary: National Institute of Pharmacy
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Russia: Ministry of Health of the Russian Federation
Ukraine: State Pharmacological Center - Ministry of Health
Germany: Federal Institute for Drugs and Medical Devices
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Italy: The Italian Medicines Agency
Netherlands: Dutch Health Care Inspectorate
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Australia: Department of Health and Ageing Therapeutic Goods Administration
China: Food and Drug Administration
New Zealand: Medsafe
Malaysia: Ministry of Health
Belgium: Federal Agency for Medicinal Products and Health Products
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Korea: Food and Drug Administration
Taiwan: Center for Drug Evaluation
Sweden: Medical Products Agency
Hungary: National Institute for Quality and Organizational Development in Healthcare and Medicines
Germany: Ethics Commission
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Janssen Research & Development, LLC:
Albuminuria
Canagliflozin
Cardiovascular outcomes
Type 2 Diabetes Mellitus
T2DM
JNJ-28431754
Antihyperglycemic Agent

Additional relevant MeSH terms:
Diabetes Mellitus, Type 2
Albuminuria
Diabetes Mellitus
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Proteinuria
Signs and Symptoms
Urination Disorders
Urologic Diseases
Urological Manifestations

ClinicalTrials.gov processed this record on October 20, 2014