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 - CANTATA

• Register: EUCTR
• Last refreshed on: 14 August 2012
• Main ID: EUCTR2009-016525-34-IT
• Date of registration: 28/09/2010
• Prospective Registration: Yes
• Primary sponsor: Janssen-Cilag International NV
• Public title: 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 - CANTATA
• Scientific title: 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 - CANTATA
• Date of first enrolment: 07/10/2010
• Target sample size: 1260
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-016525-34
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no

Countries of recruitment

Bulgaria, Czech Republic, Estonia, Greece, Italy, Latvia, Poland, Portugal, Sweden

Key inclusion & exclusion criteria

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 ? FPG <270 mg/dL (15 mmol/L) at Week -2. ? 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: ? 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 ? Women of childbearing potential must have a negative urine B human chorionic gonadotropin (B 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 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 ? Adequate compliance with the run-in period study procedures, including performance of the 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
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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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 (refer to Attachment 4, 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 (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) <60 mL/min/1.73 m2 or serum creatinine ?1.4 mg/dL (124 ?mol/L) for men and ?1.3 mg/dL (115 ?mol/L) for women ? Fasting serum triglycerides ?600 mg/dL (6.74 mmol/L) at screening (or subsequent visit if not fasting at screening) Note: a one-time repeat of the serum triglycerides is allowed, at the discretion of the investigator, if the screening value is not consistent with recent values. ? 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)


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

Health Condition(s) or Problem(s) studied

Type 2 Diabetes Mellitus With Inadequate Glycemic Control
MedDRA version: 9.1 Level: LLT Classification code 10063624

Intervention(s)

Product Name: Canagliflozin
Product Code: JNJ-28431754
Pharmaceutical Form: Capsule, hard
Current Sponsor code: JNJ-28431754
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Product Name: Canagliflozin
Product Code: JNJ-28431754
Pharmaceutical Form: Capsule, hard
Current Sponsor code: JNJ-28431754
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 300-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Trade Name: JANUVIA
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: SITAGLIPTIN
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Primary Outcome(s)

Primary end point(s): The primary efficacy endpoint will be the change in HbA1c from baseline to Week 26.

Secondary Objective: Fasting plasma glucose (FPG) Body weight Proportion of subjects with HbA1c <7.0% and <6.5% 2 hour postprandial plasma glucose (2 h PPG) after a standard meal Fasting plasma lipids (ie, low-density lipoprotein-cholesterol [LDL-C], high-density lipoprotein-cholesterol [HDL-C], total cholesterol, LDL-C to HDL-C ratio, and triglycerides) Systolic and diastolic blood pressure Time to rescue therapy and proportion of subjects receiving rescue therapy Fasting measure of beta-cell function (ie, HOMA-B) After 52 weeks of treatment, to assess the effect of canagliflozin relative to sitagliptin on: Glycemic control (HbA1c and FPG) Body weight Proportion of subjects with HbA1c <7.0% and <6.5% Fasting plasma lipids (ie, LDL-C, HDL-C, total cholesterol, LDL-C to HDL-C ratio, and triglycerides) Systolic and diastolic blood pressure

Main Objective: To assess the effect of canagliflozin relative to placebo on HbA1c after 26 weeks of treatment To assess the safety and tolerability of canagliflozin

Secondary ID(s)

2009-016525-34-LV

28431754DIA3006 INT 1