A Randomized Study to Evaluate the Effectiveness, Safety, and Tolerability of Canagliflozin in Subjects With Type 2 Diabetes Mellitus With Inadequate Glucose Control and on Metformin Monotherapy

Phase 1

• Conditions: Subjects with T2DM with inadequate glycemic control on a maximally effective dose of metformin in monotherapy; MedDRA version: 13.1Level: LLTClassification code 10063624Term: Type II diabetes mellitus inadequate controlSystem Organ Class: 10027433 - Metabolism and nutrition disorders; Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

• Registration Number: EUCTR2010-024256-28-SK
• Lead Sponsor: Janssen Cilag International NV

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-04-19
• Last Update Posted: 3 April 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 270

Inclusion Criteria

1. Be a man or woman =18 and =80 years of age with T2DM and on metformin monotherapy at a stable protocol-specified dose (=2,000 mg/day [or =1,500 mg/day, if unable to tolerate a higher dose]) for at least 8 weeks immediately prior to screening and have 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)
2. 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.
3. Fasting fingerstick glucose of =110 mg/dL (6.1 mmol/L) and <270 mg/dL (15 mmol/L)
performed at home (with documentation of the value in the subject's diary) or at the investigational site 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 the assessment of a one-time repeat fingerstick glucose (performed at home or at the investigational site) and continue in the study if the subject’s repeat fingerstick glucose
meets the criterion.
4. 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.
5. Women of childbearing potential must have a negative urine ß-human chorionic gonadotropin (ß-hCG) pregnancy test at screening and baseline (predose, Day 1)
6. Willing and able to adhere to the prohibitions and restrictions specified in this protocol
7. 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
8. Adequate compliance with the run-in period study procedures, including performance of the fasting SMBG measurements (completed at least 3 or more fasting SMBG measurements per week) with appropriate diary entries, and =80% compliance (by pill count) with singleblind 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 200
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 70

Exclusion Criteria

Diabetes-related or Metabolic
1. Has a history of diabetic ketoacidosis, T1DM, pancreas or beta-cell transplantation, or diabetes secondary to pancreatitis or pancreatectomy
2. Has 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
3. Has proliferative diabetic retinopathy for which treatment is planned during the course of the study
4. Has a history of 1 or more severe hypoglycemic episode within 6 months before screening
Note: a severe hypoglycemic episode is defined as an event that requires the help of another person.
5. Has history of hereditary glucose-galactose malabsorption or primary renal glucosuria
6. Has ongoing, inadequately controlled thyroid disorder (eg, subject has a known thyroid stimulating hormone [TSH] value that is either <0.2 or >10 mIU/L)
Note: subjects on thyroid hormone replacement therapy must be on stable doses for at least 6 weeks prior to Day 1
7. Is on either a PPAR? agonist (eg, a thiazolidinedione (TZD) [pioglitazone or rosiglitazone]), ongoing insulin therapy, another SGLT2 inhibitor, or any AHA (including agents such as colesevelam and bromocriptine that have indications in some regions for treatment of
T2DM) other than metformin, as specified in the study inclusion criteria, within 12 weeks before the screening visit
Note: subjects who have been treated with only a single dose of insulin may participate.
8. Has 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
9. Has renal disease that required treatment with immunosuppressive therapy or a history of dialysis or renal transplant.
Note: subjects with a history of treated childhood renal disease, without sequelae, may participate.
10. 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
11. Has findings on 12-lead ECG that would require urgent diagnostic evaluation or intervention (eg, new clinically important arrhythmia or conduction disturbance)
12. 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.
Note: subjects may have their blood pressure lowering medication regimen adjusted and be re-evaluated to assess this criterion (on a stable regimen for at least 4 weeks before Day 1 to be eligible).
Gastrointestinal
13. Has 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.
14. Has history of prior bariatric surgical procedure within 3 years before the screening visit.
Note: subjects with bariatric surgery more than 3 years prior to screening must be at a stable weight to be eligible to participate.
Laboratory
15. Estimated glomerular filtration rate (eGFR) (as determined by central laboratory)
<55 mL/min/1.73 m2 (or eGFR <60 mL/min

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified