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 ('CANVAS-R')
- Conditions
- diabetesDiabetes mellitus100822061001265310029149
- Registration Number
- NL-OMON45079
- Lead Sponsor
- Janssen-Cilag
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 250
- Man or woman with a diagnosis of T2DM with HbA1c level * 7.0% to * 10.5% at screening
and be either (1) not currently on AHA therapy or (2) on AHA monotherapy or combination
therapy with any approved agent: eg, sulfonylurea, metformin, pioglitazone,
alpha-glucosidase inhibitor, GLP-1 analogue, DPP-4 inhibitor, or insulin.;- History or high risk of CV events defined on the basis of either:
Age *30 years with documented symptomatic atherosclerotic CV events:
including stroke; MI; hospital admission for unstable angina; coronary artery bypass
graft; percutaneous coronary intervention (with or without stenting); peripheral
revascularization (angioplasty or surgery); symptomatic with documented
hemodynamically-significant carotid or peripheral vascular disease; or amputation
secondary to vascular disease.
2) age * 50 years with 2 or more of the following risk factors determined at the screening
visit: duration of T2DM of 10 years or more, systolic blood pressure >140 mmHg
(average of 3 readings) recorded at the Screening Visit, while the subject is on at least
one blood pressure-lowering treatment, current daily cigarette smoker, documented
micro- or macroalbuminuria (see Section 3.2, Study Design Rationale, for definition)
within one year of screening, or documented HDL-C of <1 mmol/L (<39 mg/dL) within
one year of screening.
Note: An overall target ratio of approximately 70%:30% for CV history (first
category):risk factors (second category) will be implemented (with a maximum of
approximately 40% in the second category). This target is intended to be a global ratio
and may vary by region. The proportion of subjects in these categories will be
monitored centrally.
Note: the term *documented* in the above paragraphs refers to the required information
being clearly noted in hospital/clinical records or in physician-referral documents,
copies of which should be retained in the subject*s study files.;- Women must be:
postmenopausal, defined as
o >45 years of age with amenorrhea for at least 18 months, or
o >45 years of age with amenorrhea for at least 6 months and less than 18 months
and a known serum follicle stimulating hormone (FSH) level >40 IU/L, or
o surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal occlusion),
or otherwise be incapable of pregnancy, or
o heterosexually active and practicing a highly effective method of birth control,
including hormonal prescription oral contraceptives, contraceptive injections,
contraceptive patch, intrauterine device, double-barrier method (eg, condoms,
diaphragm, or cervical cap with spermicidal foam, cream, or gel), or male partner
sterilization, consistent with local regulations regarding use of birth control methods for
subjects participating in clinical trials, for the duration of their participation in the study,
or
o not heterosexually active.
Note: subjects who are not heterosexually active at screening must agree to utilize a
highly effective method of birth control if they become heterosexually active during
their participation in the study.;- Women of childbearing potential (ie, those subjects who do not meet the postmenopausal
definition above, regardless of age) must have a negative urine pregnancy test at baseline
(Day 1) and at screening if required by local regulations (Note: a serum pre
Potential subjects who meet any of the following criteria will be excluded from participating in
the study:;Diabetes-Related/Metabolic
- History of diabetic ketoacidosis, T1DM, pancreas or beta-cell transplantation, or diabetes
secondary to pancreatitis or pancreatectomy
- History of one or more severe hypoglycemic episodes within 6 months before screening
Note: a severe hypoglycemic episode is defined as an event that requires the help of another
person.
- History of hereditary glucose-galactose malabsorption or primary renal glucosuria
- Ongoing, inadequately controlled thyroid disorder
Note: subjects on thyroid hormone replacement therapy must be on a stable dose for at least
6 weeks before Day 1.;Renal/Cardiovascular
- Renal disease that required treatment with immunosuppressive therapy or a history of
chronic dialysis or renal transplant. Note: subjects with a history of treated childhood renal
disease, without sequelae, may participate.
- Myocardial infarction, unstable angina, revascularization procedure, or cerebrovascular
accident within 3 months before screening, or a planned revascularization procedure, or
history of New York Heart Association (NYHA) Class IV cardiac disease (The Criteria
Committee of the New York Heart Association).
- Known ECG findings within 3 months before screening that would require urgent diagnostic
evaluation or intervention (eg, new clinically important arrhythmia or conduction
disturbance);Gastrointestinal
- Known history of hepatitis B surface antigen or hepatitis C antibody positive (unless known
to be associated with documented persistently stable/normal range aspartate
aminotransferase [AST] and alanine aminotransferase [ALT] levels), or other clinically
active liver disease
- Any history of or planned bariatric surgery;Laboratory
- eGFR <30 mL/min/1.73m2 at screening visit
- ALT levels >2.0 times the upper limit of normal (ULN) or total bilirubin >1.5 times the
ULN, unless in the opinion of the investigator and as agreed upon by the sponsor*s medical
officer, the findings are consistent with Gilbert*s disease;Other conditions
- History of malignancy within 5 years before screening (exceptions: squamous and basal cell
carcinomas of the skin and carcinoma of the cervix in situ, or a malignancy that in the
opinion of the investigator, with concurrence with the sponsor*s medical monitor, is
considered cured with minimal risk of recurrence)
- History of human immunodeficiency virus (HIV) antibody positive
- Subject has a current clinically important hematological disorder (eg, symptomatic anemia,
proliferative bone marrow disorder, thrombocytopenia)
- Investigator*s assessment that the subject*s life expectancy is less than 1 year, or any
condition that in the opinion of the investigator would make participation not in the best
interest of the subject, or could prevent, limit, or confound the protocol-specified safety or
efficacy assessments
- Major surgery (ie, requiring general anesthesia) within 3 months of the screening visit or any
surgery planned during the subject*s expected participation in the study (except minor
surgery, ie, outpatient surgery under local anesthesia)
- Any condition that, in the opinion of the investigator, would compromise the well-being of
the subject or prevent the subject from meeting or p
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method