A Study of the Effects of Canagliflozin on Renal and Cardiovascular Outcomes in Subjects With Type 2 Diabetes Mellitus and Diabetic Kidney Disease

• Register: EUCTR
• Last refreshed on: 7 January 2019
• Main ID: EUCTR2013-004494-28-SK
• Date of registration: 18/12/2014
• Prospective Registration: Yes
• Primary sponsor: Janssen-Cilag International NV
• Public title: A Study of the Effects of Canagliflozin on Renal and Cardiovascular Outcomes in Subjects With Type 2 Diabetes Mellitus and Diabetic Kidney Disease
• Scientific 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
• Date of first enrolment: 16/02/2015
• Target sample size: 4200
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-004494-28
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Brazil, Bulgaria, Canada, Chile, China, Colombia, Czech Republic, Egypt, France, Germany, Guatemala, Hong Kong, Hungary, India, Italy, Japan, Korea, Republic of, Lithuania, Malaysia, Mexico, New Zealand, Philippines, Poland, Romania, Russian Federation, Serbia, Slovakia, South Africa, Spain, Sri Lanka, Taiwan, Ukraine, United Arab Emirates, United Kingdom, United States

Contacts

• Name: Clinical Registry Group
• Affiliation: Janssen Pharmaceutica NV

• Name: Clinical Registry Group
• Affiliation: Janssen Pharmaceutica NV

Key inclusion & exclusion criteria

Inclusion criteria:
-T2DM with a HbA1c = 6.5% to = 12%, with an eGFR = 30 to < 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 an urine albumin to creatinine ratio (UACR) > 300 mg/g to = 5000 mg/g
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 2800
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1400

Exclusion criteria:
- History of diabetic ketoacidosis or type 1 diabetes mellitus
- History of hereditary glucose-galactose malabsorption or primary
renal glucosuria
-History of hyperkalemia requiring treatment, or blood potassium level >5.5 mmol/L at baseline.
-Combination use of ACEi and ARB
-Use of mineralcorticoid receptor antagonists (MRA) or direct renin inhibitor (DRI)
- 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
-Blood potassium level>5.5 mmol/L during screening


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Type 2 Diabetes Mellitus and Diabetic Nephropathy
MedDRA version: 20.1 Level: LLT Classification code 10045242 Term: Type II diabetes mellitus System Organ Class: 100000004861

Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

Intervention(s)

Trade Name: Invokana
Product Name: Canagliflozin
Product Code: JNJ-28431754-ZAE
Pharmaceutical Form: Capsule
INN or Proposed INN: CANAGLIFLOZIN
CAS Number: 928672-86-0
Other descriptive name: CANAGLIFLOZIN
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: In subjects with T2DM, Stage 2 or 3 CKD and macroalbuminuria who are receiving standard of care, to assess the efficacy of canagliflozin relative to placebo in reducing:
- The composite endpoint of CV death and hospitalized congestive heart failure
- The composite endpoint of CV death, non-fatal myocardial infarction (MI), and non-fatal stroke (ie, 3 point major adverse cardiac event [MACE])
- Hospitalized congestive heart failure
- The renal composite endpoint of ESKD, doubling of serum creatinine, and renal death
- CV death
- All-cause death
- The CV composite endpoint of CV death, non-fatal MI, non-fatal stroke, hospitalized congestive heart failure, and hospitalized unstable angina

Main Objective: In subjects with T2DM, Stage 2 or 3 CKD and macroalbuminuria who are receiving standard of care, to assess the efficacy of canagliflozin relative to placebo in reducing the composite endpoint of ESKD, doubling of serum creatinine, and renal or CV death.

Timepoint(s) of evaluation of this end point: Baseline, up to approximately Month 66

Primary end point(s): -Time to the first occurrence of an event in the primary composite
endpoint

Secondary Outcome(s)

Secondary end point(s): -Time to the first occurrence of an event in the CV composite endpoint
-Time to the first occurrence of an event in the renal composite endpoint
-Time to all-cause death
-Time to the first occurrence of an event in the CV Composite Endpoint of CV Death, non-fatal MI, and non-fatal stroke (ie, 3-point MACE); and Hospitalised Congestive Heart Failure
-Time to CV death

Timepoint(s) of evaluation of this end point: Baseline, up to approximately Month 66

Secondary ID(s)

28431754DNE3001

2013-004494-28-GB

Source(s) of Monetary Support

Janssen Research and Development, LLC