A Randomised Double-Blind Placebo-Controlled Multicenter Study with Extension to Evaluate the Efficacy Safety and Tolerability of Canagliflozin in the Treatment of Subjects with Type 2 DiabetesMellitus Who Have Moderate Renal Impairment
- Conditions
- Metabolic and Endocrine - DiabetesType 2 diabetes in patietns with moderate renal impairment.
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 272
1) Man or woman with Type 2 diabetes Mellitus (T2DM), age =25 years, and either not on an anti hyperglycemic agent (AHA) or on any AHA in monotherapy or combination therapy (including oral or non-oral agents).
2) HbA1c =7.0% to =10.5% at screening and Week -2 visits.
3) On a stable AHA regimen consistent with local prescribing information (ie, local
label[s]) for at least 8 weeks (and 12 weeks for peroxisome proliferator-activated receptors (PPAR) agents [eg, rosiglitazone or pioglitazone]) before Week -2.
4) Have moderate renal impairment, as defined by eGFR values (estimated by the
4-variable Modification of Diet in Renal Disease (MDRD) equation) =30 and <50 mL/min/1.73 m2 at both the screening and
the Week -2 visit, with generally stable renal function, as demonstrated by =25%
decline in eGFR at Week-2 relative to the screening visit value
5) Fasting plasms glucose (FPG) =270 mg/dL (15 mmol/L) at
Week-2
6) Site fasting fingerstick glucose of =110 mg/dL (6.1 mmol/L) and =270 mg/dL
(15 mmol/L) on Day 1
Women must be on a highly effictive method of birth control
7) Women of childbearing potential must have a negative urine beta-human chorionic
gonadotropin (beta-hCG) pregnancy test at screening and baseline (predose, Day 1).
8) Willing and able to adhere to the prohibitions and restrictions specified in this
protocol.
9) Subjects must have signed an informed consent document indicating that they
understand the purpose of and procedures required for the study and are willing to
participate in the study.
10) To participate in the optional pharmacogenomic component of this study, subjects must have signed the informed consent form for pharmacogenomic research
indicating willingness to participate in the pharmacogenomic component of the study
(where local regulations permit). Refusal to give consent for this component does not
exclude a subject from participation in the clinical study.
11) Adequate compliance with the run-in period study procedures, including performance of the self monitored blood glucose (SMBG) measurements (completed at least 3 or more SMBG measurements per week) with appropriate diary entries, and =80% compliance (by pill count) with single-blind placebo capsules.
1) History of diabetic ketoacidosis, type 1 diabetes mellitus (T1DM), pancreas or beta-cell transplantation, or
diabetes secondary to pancreatitis or pancreatectomy
2) Repeated (ie, 2 or more over a 1-week period) FPG and/or fasting SMBG glucose
measurements >270 mg/dL (15 mmol/L) during the pretreatment phase, despite
reinforcement of diet and exercise counseling
3) Have proliferative diabetic retinopathy for which treatment is planned during the
course of the study
4) History of 1 or more severe hypoglycemic episode within 6 months before screening.
5) History of hereditary glucose-galactose malabsorption or primary renal glucosuria
6) Ongoing, inadequately controlled thyroid disorder (eg, subject has a known thyroid
stimulating hormone [TSH] value that is either <0.2 or >10 mIU/L)
7) Ongoing eating disorder or significant weight loss or weight gain within 12 weeks,
defined as an increase or decrease of 5% in body weight based upon clinic-based
measurement or, if not available, subject report
8) Renal disease that required treatment with immunosuppressive therapy or a history of dialysis or renal transplant
9) Presence of nephrotic syndrome (eg, severe proteinuria with hypoalbuminemia and/or edema), or inflammatory renal disease (eg, acute interstitial nephritis, acute or rapidly-progressive glomerulonephritis)
10) Subject is likely to require dialysis or transplantation during participation in the study
11) Myocardial infarction, unstable angina, revascularization procedure (eg, stent or
bypass graft surgery), or cerebrovascular accident within 3 months before screening,
or revascularization procedure is planned, or subject has a history of New York Heart
12) Association (NYHA) Class III-IV cardiac disease (refer to Attachment 3, New York
Heart Association Classification of Cardiac Disease, for a description of the classes)
13) Findings on 12-lead ECG that would require urgent diagnostic evaluation or
intervention (eg, new clinically important arrhythmia or conduction disturbance)
14) Uncontrolled hypertension (ie, using an average of 3 seated blood pressure readings with a diastolic blood pressure =100 mmHg or systolic blood pressure =160 mmHg) at Week -2
15) History of hepatitis B surface antigen or hepatitis C antibody positive (unless associated with documented persistently stable/normal range aspartate
aminotransferase [AST] and Alanine Transaminase (ALT) levels, or other clinically active liver disease
16) History of prior bariatric surgical procedure within 3 years before the screening visit
17) Fasting serum triglycerides =600 mg/dL (6.74 mmol/L) at screening (or subsequent
visit if not fasting at screening)
18) Alanine aminotransferase level >2.0 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)
19) Hemoglobin concentration <10 g/L at screening
20) History of malignancy within 5 years before screening (exceptions: squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, 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)
21) Clinically important hematologic disorder (eg, symptomatic anemia, proliferative bone
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To assess safety and tolerability, by assessing adverse events during the duration of the trial and proportion of subjects receiving rescue therapy and time to rescue therapy. Important measures of renal safety will be the eGFR, based upon serum creatinine, and Albumin Creatinin Ratio (ACR) measured in the first morning urine collection[ After 26 weeks of treatment];To assess the effect of canagliflozin relative to placebo on glycated hemoglobin (HbA1c). HbA1c is a test that measures the amount of glycated hemoglobin in the blood.[ After 26 weeks of treatment]
- Secondary Outcome Measures
Name Time Method