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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier:
NCT00642278
First received: March 21, 2008
Last updated: July 15, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention Phase
Diabetes Mellitus, Type II
Diabetes Mellitus, Non Insulin Dependent
Drug: Canagliflozin (JNJ-28431754)
Drug: Sitagliptin
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:

Primary Outcome Measures:
  • Change in HbA1c From Baseline to Week 12 [ Time Frame: Day 1 (Baseline) and Week 12 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Change in Fasting Plasma Glucose (FPG) From Baseline to Week 12 [ Time Frame: Day 1 (Baseline) and Week 12 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.


Enrollment: 451
Study Start Date: April 2008
Study Completion Date: January 2009
Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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).
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: Placebo
One matching placebo capsule orally (by mouth) once or twice daily for 12 weeks.
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).
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: Placebo
One matching placebo capsule orally (by mouth) once or twice daily for 12 weeks.
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).
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: Placebo
One matching placebo capsule orally (by mouth) once or twice daily for 12 weeks.
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).
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: Placebo
One matching placebo capsule orally (by mouth) once or twice daily for 12 weeks.
Experimental: Canagliflozin 300 mg twice daily
Each patient will receive 300 mg of canagliflozin (JNJ-28431754) twice daily for 12 weeks.
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
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).
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.
Placebo Comparator: Placebo
Each patient will receive matching placebo twice daily for 12 weeks.
Drug: Placebo
One matching placebo capsule orally (by mouth) once or twice daily for 12 weeks.

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).

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00642278

  Show 85 Study Locations
Sponsors and Collaborators
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Investigators
Study Director: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
  More Information

No publications provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier: NCT00642278     History of Changes
Other Study ID Numbers: CR014587, 28431754DIA2001
Study First Received: March 21, 2008
Results First Received: April 1, 2013
Last Updated: July 15, 2013
Health Authority: United States: Food and Drug Administration
Great Britain: Medicines and Healthcare Products Regulatory Agency
United States: Federal Government

Keywords provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:
Type 2 diabetes mellitus
Metformin
Hemoglobin A1c

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Sitagliptin
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Hypoglycemic Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 24, 2014