An Efficacy, Safety, and Tolerability Study of Canagliflozin (JNJ-28431754) in Patients With Type 2 Diabetes

• ClinicalTrials.gov Identifier: NCT00642278
• Recruitment Status: Completed
• First Posted: March 25, 2008
• Results First Posted: May 17, 2013
• Last Update Posted: July 19, 2013
• Sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
• Information provided by (Responsible Party): Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Tracking Information

• First Submitted Date: March 21, 2008
• First Posted Date: March 25, 2008
• Results First Submitted Date: April 1, 2013
• Results First Posted Date: May 17, 2013
• Last Update Posted Date: July 19, 2013
• Study Start Date: April 2008
• Actual Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 1, 2013)

Change in HbA1c From Baseline to Week 12 [ Time Frame: Day 1 (Baseline) and Week 12 ]

The table below shows the mean change in HbA1c from Baseline to Week 12 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin or sitagliptin group minus placebo) in the least-squares mean change.

• Original Primary Outcome Measures (submitted: March 24, 2008): The primary efficacy endpoint is the change in hemoglobin A1c (A1C) from baseline through Week 12.

Current Secondary Outcome Measures (submitted: April 1, 2013)

• Change in Fasting Plasma Glucose (FPG) From Baseline to Week 12 [ Time Frame: Day 1 (Baseline) and Week 12 ]
  The table below shows the mean change in FPG from Baseline to Week 12 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin or sitagliptin group minus placebo) in the least-squares mean change.
• Percentage of Patients With Symptoms of Hypoglycemia [ Time Frame: Up to Week 12 ]
  The table below shows the percentage of patients who experienced symptomatic hypoglycemic events between Baseline and Week 12.
• Change in Overnight Urine Glucose/Creatinine Ratio From Baseline to Week 12 [ Time Frame: Day 1 (Baseline) and Week 12 ]
  The table below shows the mean change in overnight urine glucose/creatinine ratio from Baseline to Week 12 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin or sitagliptin group minus placebo) in the least-squares mean change.
• Absolute Change in Body Weight From Baseline to Week 12 [ Time Frame: Day 1 (Baseline) and Week 12 ]
  The table below shows the mean absolute change in body weight from Baseline to Week 12 for each treatment group.
• Percent Change in Body Weight From Baseline to Week 12 [ Time Frame: Day 1 (Baseline) and Week 12 ]
  The table below shows the mean percent change in body weight from Baseline to Week 12 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin or sitagliptin group minus placebo) in the least-squares mean change.

• Original Secondary Outcome Measures (submitted: March 24, 2008): The change in A1C from baseline to Weeks 6, 9, and 12; the proportion of subjects with A1C of <6.5% and <7.0% at Week 12; the change in 7-point self-monitored blood glucose profiles from baseline to Week 6 and 12
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: An Efficacy, Safety, and Tolerability Study of Canagliflozin (JNJ-28431754) in Patients With Type 2 Diabetes
• Official Title: A Randomized, Double-Blind, Placebo-Controlled, Double-Dummy, Parallel Group, Multicenter, Dose-Ranging Study in Subjects With Type 2 Diabetes Mellitus to Evaluate the Efficacy, Safety, and Tolerability of Orally Administered SGLT2 Inhibitor JNJ-28431754 With Sitagliptin as a Reference Arm
• Brief Summary: The purpose of this study is to evaluate the effectiveness, safety, and tolerability of JNJ-28431754 compared with placebo in patients with type 2 diabetes.
• Detailed Description: Type 2 diabetes mellitus is a metabolic disorder that is characterized by decreased secretion of insulin by the pancreas and resistance to the action of insulin in various tissues (muscle, liver, and adipose), which results in impaired glucose uptake. Chronic hyperglycemia leads to progressive impairment of insulin secretion and to insulin resistance of peripheral tissues in diabetes (so-called glucose toxicity), which further worsens control of blood glucose. In addition, chronic hyperglycemia is a major risk factor for complications, including heart disease, retinopathy, nephropathy, and neuropathy. Although numerous treatments have been developed for the treatment of diabetes and individual agents may be highly effective for some patients, it is still difficult to maintain optimal glycemic control in most patients with diabetes. This is a randomized, double-blind, placebo-controlled, parallel group, multicenter, dose-ranging study to determine the efficacy, safety and tolerability of JNJ-28431754 taken orally over 12 weeks, compared with placebo, in the treatment of Type 2 diabetes mellitus. The primary clinical hypothesis is that JNJ-28431754 is superior to placebo as measured by the change in hemoglobin A1c from baseline through Week 12 in the treatment of type 2 diabetes mellitus. Subject safety will be monitored throughout the study using spontaneous adverse event reporting, clinical laboratory tests (hematology, serum chemistry, urinalysis); severe and serious hypoglycemic episodes, assessment of urinary albumin excretion and markers of proximal renal tubular function; pregnancy tests; electrocardiograms (ECGs); vital sign measurements; physical examinations, assessment of calcium and phosphate homeostasis, bone formation and resorption markers, and hormones regulating calcium and phosphorus homeostasis; and vaginal and urine sample collection for fungal and bacterial culture in subjects with symptoms consistent with vulvovaginal candidiasis (VVC) or urinary tract infection (UTI).
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• Diabetes Mellitus, Type II
• Diabetes Mellitus, Non Insulin Dependent

Intervention

• Drug: Canagliflozin (JNJ-28431754)
  One 50 mg, 100 mg, 200 mg, or 300 mg over-encapsulated tablet orally (by mouth) once daily for 12 weeks or one 300 mg over-encapsulated tablet orally twice daily for 12 weeks.
  Other Name: JNJ-28431754
• Drug: Sitagliptin
  One 100 mg over-encapsulated tablet orally (by mouth) once daily for 12 weeks.
• Drug: Placebo
  One matching placebo capsule orally (by mouth) once or twice daily for 12 weeks.

Study Arms

• Experimental: Canagliflozin 50 mg daily
  Each patient will receive 50 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).
  Interventions:

  • Drug: Canagliflozin (JNJ-28431754)
  • Drug: Placebo
• Experimental: Canagliflozin 100 mg daily
  Each patient will receive 100 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).
  Interventions:

  • Drug: Canagliflozin (JNJ-28431754)
  • Drug: Placebo
• Experimental: Canagliflozin 200 mg daily
  Each patient will receive 200 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).
  Interventions:

  • Drug: Canagliflozin (JNJ-28431754)
  • Drug: Placebo
• Experimental: Canagliflozin 300 mg daily
  Each patient will receive 300 mg of canagliflozin (JNJ-28431754) once daily (in the morning) for 12 weeks with matching placebo capsule once daily (in the evening).
  Interventions:

  • Drug: Canagliflozin (JNJ-28431754)
  • Drug: Placebo
• Experimental: Canagliflozin 300 mg twice daily
  Each patient will receive 300 mg of canagliflozin (JNJ-28431754) twice daily for 12 weeks.
  Intervention: Drug: Canagliflozin (JNJ-28431754)
• Active Comparator: Sitagliptin 100 mg daily
  Each patient will receive 100 mg of sitagliptin once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).
  Interventions:

  • Drug: Sitagliptin
  • Drug: Placebo
• Placebo Comparator: Placebo
  Each patient will receive matching placebo twice daily for 12 weeks.
  Intervention: Drug: Placebo

Publications *

• Nyirjesy P, Zhao Y, Ways K, Usiskin K. Evaluation of vulvovaginal symptoms and Candida colonization in women with type 2 diabetes mellitus treated with canagliflozin, a sodium glucose co-transporter 2 inhibitor. Curr Med Res Opin. 2012 Jul;28(7):1173-8. doi: 10.1185/03007995.2012.697053. Epub 2012 Jun 14.
• Nicolle LE, Capuano G, Ways K, Usiskin K. Effect of canagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, on bacteriuria and urinary tract infection in subjects with type 2 diabetes enrolled in a 12-week, phase 2 study. Curr Med Res Opin. 2012 Jul;28(7):1167-71. doi: 10.1185/03007995.2012.689956. Epub 2012 May 15.
• Rosenstock J, Aggarwal N, Polidori D, Zhao Y, Arbit D, Usiskin K, Capuano G, Canovatchel W; Canagliflozin DIA 2001 Study Group. Dose-ranging effects of canagliflozin, a sodium-glucose cotransporter 2 inhibitor, as add-on to metformin in subjects with type 2 diabetes. Diabetes Care. 2012 Jun;35(6):1232-8. doi: 10.2337/dc11-1926. Epub 2012 Apr 9.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 12, 2009): 451
• Original Estimated Enrollment (submitted: March 24, 2008): 420
• Actual Study Completion Date: January 2009
• Actual Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Patients must have a diagnosis of type 2 diabetes mellitus
• Hemoglobin A1c levels >=7% and <=10.5%
• taking a stable daily dose of metformin
• Body mass index (BMI) 25 to 45 kg/m2 except those of Asian descent who must have a BMI of 24 to 45 kg/m2
• Stable body weight
• Serum creatinine <=1.5 mg/dL (132.6 umol/L) for men and <=1.4 mg/dL (123.76 umol/L) for women

Exclusion Criteria:

• Patients must not have prior exposure or known contraindication or suspected hypersensitivity to canagliflozin (JNJ-28431754)
• Known contraindication or suspected hypersensitivity to sitagliptin or metformin
• A history of diabetic ketoacidosis or type 1 diabetes mellitus
• History of pancreas or beta-cell transplantation
• History of active proliferative diabetic retinopathy
• History of hereditary glucose-galactose malabsorption or primary renal glucosuria

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Bulgaria, Canada, Czech Republic, India, Malaysia, Mexico, Poland, Puerto Rico, Romania, Russian Federation, United Kingdom, United States
• Removed Location Countries: Ireland, Sweden

Administrative Information

• NCT Number: NCT00642278
• Other Study ID Numbers: CR014587; 28431754DIA2001 ( Other Identifier: Johnson & Johnson Pharmaceutical Research & Development, L.L.C. )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
• Study Sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
• Collaborators: Not Provided

Investigators

• Study Director: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial; Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

• PRS Account: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
• Verification Date: July 2013