A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Study to Evaluate the Efficacy, Safety, and Tolerability of Canagliflozin as Monotherapy in the Treatment of Subjects With Type 2 Diabetes Mellitus Inadequately Controlled With Diet and Exercise - The CANTATA-M Trial / (CANagliflozin Treatment and Trial Analysis – Monotherapy)
- Conditions
- Type 2 Diabetes MellitusMedDRA version: 12.1Level: LLTClassification code 10045242Term: Type II diabetes mellitus
- Registration Number
- EUCTR2009-015883-32-EE
- Lead Sponsor
- Janssen-Cilag International NV
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 450
For Main Study:
• Man or woman > or =18 and < or =80 years of age with T2DM who meet 1 of the 2 following criteria:
–Not on AHA therapy at screening (off for at least 12 weeks) with an HbA1c of > or =7% and < or =10% at the screening (or prescreening) visit (Note: if HbA1c measurement is not within 3 weeks of the Week -2 visit, HbA1c testing must be repeated at the Week -2 visit to assess this inclusion criterion)
or
–On an oral AHA in monotherapy (except a PPAR gamma agonist, eg, thiazolidinedione [TZD]) or on low-dose combination therapy with metformin (< or =1,000 mg) and SU (at < or =50% of maximally or near maximally effective doses as defined in Attachment 3) with an HbA1c of > or =6.5% and , or =9.5% at the screening (or prescreening) visit and has a Week -2 (after the 8 week diet and exercise/and AHA washout period) HbA1c of > or =7% and < or =10%
•FPG <270 mg/dL (15 mmol/L) at Week -2.
Note: at the investigator’s discretion, based upon review of recent SMBG values, subjects not meeting the Week -2 FPG criterion may return to the investigational site within 7 days for a one-time repeat FPG and continue in the study if the subject’s repeat FPG meets the criteria.
•Site fasting fingerstick glucose of =110 mg/dL (6.1 mmol/L) and <270 mg/dL (15 mmol/L) on Day 1.
Inclusion Criteria – High Glycemic Cohort Substudy
•Man or woman =18 and < or =80 years of age with T2DM who meet 1 of the 2 following criteria
–Not on AHA therapy at screening (off for at least 12 weeks) with an HbA1c of >10% and < or =12% at the screening (or prescreening) visit (Note: if HbA1c measurement is not within 3 weeks of the Week -2 visit, HbA1c testing must be repeated at the Week -2 visit to assess this inclusion criterion) or
–On an oral AHA in monotherapy (except a PPAR gamma agonist, eg, TZD) or on low dose combination therapy with metformin (< or =1,000 mg) and SU (at < or =50% of maximally or near maximally effective doses as defined in Attachment 3) with an HbA1c of > or =6.5% and < or =9.5% at the screening (or prescreening) visit and has a Week -2 visit (after the 8 week diet and exercise and AHA washout period) HbA1c of >10% and < or =12%
•FPG < or =350 mg/dL (19.44 mmol/L) at Week -2 visit
Note: at the investigator’s discretion, based upon review of recent SMBG values, subjects not meeting this FPG criterion may return to the investigational site within 7 days for a one-time repeat FPG and continue in the study if the subject’s repeat FPG meets the criteria.
Inclusion Criteria – Main Study and High Glycemic Cohort Substudy
•Women must be:
–postmenopausal, defined as
-- >45 years of age with amenorrhea for at least 18 months, or
-- >45 years of age with amenorrhea for at least 6 months and <18 months and a serum follicle stimulating hormone (FSH) level >40 IU/mL, or
–surgically sterile (have had a hysterectomy or bilateral oophorectomy, or tubal ligation) or otherwise be incapable of pregnancy, or
–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 studies, for the duration of their participation in the study, or
–not heterosexually active.
Main Study and High Glycemic Cohort Substudy
Diabetes-related or Metabolic
•Repeated FPG and/or fasting SMBG glucose measurements >270 mg/dL (15 mmol/L) during the pretreatment phase, despite reinforcement of diet and exercise counseling.
Note: during the single-blind placebo run-in period, subjects eligible for the high glycemic cohort substudy based upon screening visit or Week -2 HbA1c measurement, may continue in the study if their FPG and/or SMBG values are < or =350 mg/dL (19.44 mmol/L)
•History of diabetic ketoacidosis, T1DM, pancreas or beta cell transplantation, or diabetes secondary to pancreatitis or pancreatectomy.
•Have proliferative diabetic retinopathy for which treatment is planned during the course of the study
•History of 1 or more severe hypoglycemic episodes within 6 months before screening.
•History of hereditary glucose-galactose malabsorption or primary renal glucosuria
•Ongoing, inadequately controlled thyroid disorder (eg, thyroid stimulating hormone [TSH] value that is either <0.2 or >10 mIU/L).
•Fasting C-peptide <0.7 pmol/L in subjects for whom the investigator cannot reasonably exclude T1DM based upon clinical evaluation.
•On either a PPARgamma agonist (eg, pioglitazone or rosiglitazone), or required ongoing insulin therapy within 12 weeks before the screening visit
•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
Renal/Cardiovascular
•Renal disease that required treatment with immunosuppressive therapy or a history of dialysis or renal transplant.
•Myocardial infarction, unstable angina, revascularization procedure, or cerebrovascular accident within 3 months before screening, or revascularization procedure is planned, or subject has a history of New York Heart Association (NYHA) Class III-IV cardiac disease (refer to Attachment 5, New York Heart Association Classification of Cardiac Disease, for a description of the classes).
•Findings on 12-lead ECG that would require urgent diagnostic evaluation or intervention
•Uncontrolled hypertension (ie, using an average of 3 seated blood pressure readings with a diastolic blood pressure > or =100 mmHg or systolic blood pressure > or =160 mmHg) at Week -2.
Gastrointestinal
•History of hepatitis B surface antigen or hepatitis C antibody positive (unless associated with documented persistently stable/normal range aspartate aminotransferase [AST] and ALT levels), or other clinically active liver disease.
•History of prior bariatric surgical procedure within 3 years before the screening visit.
Laboratory
•Estimated eGFR <50 mL/min/1.73m2 at screening (provided by the central laboratory)
•Fasting serum triglycerides > or =600 mg/dL (6.74 mmol/L) at screening (or subsequent visit if not fasting at screening).
•Alanine aminotransferase level >2.0 times the 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)
Other conditions
•History of malignancy within 5 years before screening (eg, any evidence of active disease within 5 years, or diagnosis of malignancy within this period) Note: subjects with squamous or basal cell carcinomas of the skin carcinomas in situ of the cervi
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method