Evaluation of the Effects of Canagliflozin on Renal and Cardiovascular Outcomes in Participants With Diabetic Nephropathy (CREDENCE)

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by Janssen Research & Development, LLC
Sponsor:
Collaborator:
The George Institute for Global Health, Australia
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT02065791
First received: February 17, 2014
Last updated: October 8, 2014
Last verified: October 2014
  Purpose

The goal of this study is to assess whether canagliflozin has a renal and vascular protective effect in reducing the progression of renal impairment relative to placebo in participants with type 2 diabetes mellitus (T2DM), Stage 2 or 3 chronic kidney disease (CKD) and macroalbuminuria, who are receiving standard of care including a maximum tolerated labeled daily dose of an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB).


Condition Intervention Phase
Diabetes Mellitus, Type 2
Diabetic Nephropathies
Drug: Canagliflozin
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Event-driven, Placebo-controlled, Multicenter Study of the Effects of Canagliflozin on Renal and Cardiovascular Outcomes in Subjects With Type 2 Diabetes Mellitus and Diabetic Nephropathy

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Time to the first occurrence of an event in the primary composite endpoint [ Time Frame: Baseline, up to Month 66 ] [ Designated as safety issue: Yes ]
    The primary composite endpoint of the study includes end-stage kidney disease (ESKD), doubling of serum creatinine, renal or cardiovascular (CV) death.


Secondary Outcome Measures:
  • Time to the first occurrence of an event in the CV composite endpoint [ Time Frame: Baseline, up to Month 66 ] [ Designated as safety issue: Yes ]
    The CV composite endpoint includes CV death, non-fatal myocardial infarction (MI), non-fatal stroke, hospitalized congestive heart failure and hospitalized unstable angina.

  • Time to the first occurrence of an event in the renal composite endpoint [ Time Frame: Baseline, up to Month 66 ] [ Designated as safety issue: Yes ]
    The renal composite endpoint includes ESKD, doubling of serum creatinine, and renal death.

  • Time to all-cause death [ Time Frame: Baseline, up to Month 66 ] [ Designated as safety issue: Yes ]
    All deaths occurring during the study from any cause.


Estimated Enrollment: 3700
Study Start Date: February 2014
Estimated Study Completion Date: February 2019
Estimated Primary Completion Date: February 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Canagliflozin 100 mg
Each participant will receive 100 mg of canagliflozin once daily
Drug: Canagliflozin
One 100 mg over-encapsulated tablet orally once daily
Placebo Comparator: Placebo
Each participant will receive matching placebo once daily
Drug: Placebo
One matching placebo capsule orally (by mouth) once daily

Detailed Description:

This is a randomized (the study medication is assigned by chance), double-blind (neither physician nor participant knows the identity of the assigned treatment), placebo-controlled (an inactive substance that is compared with a medication to test whether the medication has a real effect), parallel-group, multicenter study of the effects of canagliflozin on renal and cardiovascular outcomes in participants with type 2 diabetes mellitus (T2DM) and diabetic nephropathy, who are receiving standard of care including a maximum tolerated daily dose of an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB).

The study will consist of a pretreatment phase (several weeks), and a double-blind treatment phase (up to 66 months). During the pretreatment phase all participants will also receive diet/exercise counseling for lipid and blood pressure management as well as counseling on renal and cardiovascular (CV) risk factor medication. A post-treatment follow-up contact or visit will take place approximately 30 days after the last dose of study drug or the completion of the study. The total duration of the study is estimated to be about 5.5 years. Approximately 3,700 participants will be randomized in a 1:1 ratio to canagliflozin or matching placebo. Participants randomized to canagliflozin will receive a dose of 100 mg once daily. The overall safety and tolerability of canagliflozin will be evaluated by collecting information on adverse events, laboratory tests, vital signs (pulse, blood pressure), physical examination, and body weight.

  Eligibility

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

Inclusion Criteria:

  • Type 2 diabetes mellitus with an HbA1c >= 6.5% and <=10.5%, with an estimated glomerular filtration rate (eGFR) of >= 30 and < 90 mL/min/1.73m2
  • Participants need to be on a maximum tolerated labeled daily dose of an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) for at least 4 weeks prior to randomization
  • Must have a urine albumin to creatinine ratio (UACR) of > 300 mg/g and <= 5000 mg/g

Exclusion Criteria:

  • History of diabetic ketoacidosis or type 1 diabetes mellitus
  • History of hereditary glucose-galactose malabsorption or primary renal glucosuria
  • Renal disease that required treatment with immunosuppressive therapy
  • Known significant liver disease
  • Current or history of New York Heart Association (NYHA) Class IV heart failure
  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: NCT02065791

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 173 Study Locations
Sponsors and Collaborators
Janssen Research & Development, LLC
The George Institute for Global Health, Australia
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: NCT02065791     History of Changes
Other Study ID Numbers: CR103517, 2013-004494-28, 28431754DNE3001
Study First Received: February 17, 2014
Last Updated: October 8, 2014
Health Authority: United States: Food and Drug Administration
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Brazil: National Health Surveillance Agency
Bulgaria: Bulgarian Drug Agency
Canada: Health Canada
China: Food and Drug Administration
Czech Republic: State Institute for Drug Control
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Korea: Food and Drug Administration
Hong Kong: Department of Health
Mexico: Federal Commission for Protection Against Health Risks
Romania: National Medicines Agency
South Africa: Medicines Control Council
Hungary: National Institute of Pharmacy
Italy: The Italian Medicines Agency
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Russia: Ministry of Health of the Russian Federation
Spain: Agencia Española de Medicamentos y Productos Sanitarios
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Ukraine: State Pharmacological Center - Ministry of Health
Malaysia: Ministry of Health

Keywords provided by Janssen Research & Development, LLC:
Diabetes Mellitus, Type 2
Diabetic Nephropathies
Canagliflozin
JNJ-28431754
End-Stage Kidney Disease
Chronic Kidney Disease
Macroalbuminuria

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Kidney Diseases
Diabetic Nephropathies
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Urologic Diseases
Diabetes Complications

ClinicalTrials.gov processed this record on October 19, 2014