A Randomized, Double-Blind, Placebo and Active-Controlled, 4-Arm, Parallel-Group, Multicenter Study to Evaluate the Efficacy, Safety, and Tolerability of JNJ-28431754 (Canagliflozin) Compared with Sitagliptin and Placebo in the Treatment of Subjects With Type 2 Diabetes Mellitus With Inadequate Glycemic Control on Metformin Monotherapy. - The CANTATA-D Trial (CANagliflozin Treatment and Trial

Conditions: Type 2 Diabetes Mellitus With Inadequate Glycemic Control on Metformin Monotherapy
MedDRA version: 12.1Level: LLTClassification code 10067585Term: Type 2 diabetes mellitus

Registration Number: EUCTR2009-016525-34-PT

Lead Sponsor: Janssen-Cilag International NV

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 1260

Inclusion Criteria

•Man or woman =18 and =80 years of age with T2DM who meet 1 of the following 4 criteria:
On metformin IR monotherapy at a stable protocol-specified dose* for at least 8 weeks before screening and has an HbA1c of =7.0% and =10.5% at screening (or at Week -2, if screening measurement is more than 3 weeks before Week -2)
or
–On metformin ER monotherapy at a protocol-specified dose* with an HbA1c of =7.0% and =10.5% at screening and has a Week -2 visit HbA1c of =7.0% and =10.5%, after at least 8 weeks on a stable protocol-specified dose* of metformin IR
or
–On metformin monotherapy (IR or ER) at a dose <2,000 mg/day with an HbA1c of =7.5% and =11.0% at screening and has a Week -2 visit HbA1c of =7.0% and =10.5%, after at least 8 weeks on a stable protocol-specified dose* of metformin IR
or
On metformin (IR or ER) in combination with an SU with an HbA1c of =6.5% and =9.5% at screening and has a Week -2 visit HbA1c of =7.0% and =10.5%, after at least 8 weeks on a stable protocol-specified dose* of metformin IR
*Protocol-specified dose of metformin: =2,000 mg/day (or =1,500 mg/day, if unable to tolerate a higher dose)
•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 criterion.
•Site fasting fingerstick glucose of =110 mg/dL (6.1 mmol/L) and <270 mg/dL (15 mmol/L) on Day 1
Note: at the investigator’s discretion, based upon review of recent SMBG values, subjects not meeting the Day 1 criterion may return to the investigational site within 7 days for a one-time repeat fingerstick glucose and continue in the study if the subject’s repeat fingerstick glucose meets the criterion.
•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, 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, and 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
–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 must have a negative urine ß human chorionic gonadotropin (ß hCG) pregnancy test at screening and baseline (predose, Day 1)
•Willing and able to adhere to the prohibitions and restrictions specified in this protocol
•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
•To participate in the optional pharmacogenomic component

Exclusion Criteria

Diabetes-related or Metabolic
•History of diabetic ketoacidosis, T1DM, pancreas or beta-cell transplantation, or diabetes secondary to pancreatitis or pancreatectomy
•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 pre-treatment phase, despite reinforcement of diet and exercise counseling
•Have proliferative diabetic retinopathy for which treatment is planned during the course of the study
•History of 1 or more severe hypoglycemic episode within 6 months before screening
•History of hereditary glucose-galactose malabsorption or primary renal glucosuria
•Ongoing, inadequately controlled thyroid disorder (eg, subject has a known thyroid stimulating hormone [TSH] value that is either <0.2 or >10 mIU/L)
•On either a PPAR? agonist (eg, a thiazolidinedione (TZD) [pioglitazone or rosiglitazone]) or ongoing insulin therapy within 12 weeks before the screening visit
•Ongoing eating disorder or significant weight loss or weight gain within 12 weeks before the screening visit, 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 (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 Association (NYHA) Class III-IV cardiac disease
•Findings on 12-lead ECG that would require urgent diagnostic evaluation or intervention (eg, new clinically important arrhythmia or conduction disturbance)
•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.
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 glomerular filtration rate (eGFR) <55 mL/min/1.73 m2 (or <60 mL/min/1.73 m2 if based upon restriction of metformin use in the metformin local label) or serum creatinine =1.4 mg/dL (124 µmol/L) for men and =1.3 mg/dL (115 µmol/L) for women
•Fasting serum triglycerides =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 (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)
•Clinically important hematologic disorder (eg, symptomatic anemia, proliferative bone marrow disorder, thrombocytopenia)
•History of human immunodeficiency virus (HIV