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

Diabetes Mellitus, Type II Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00642278
• Other study ID #: CR014587
• Secondary ID: 28431754DIA2001
• Status: Completed
• Phase: Phase 2
• First received: March 21, 2008
• Last updated: July 15, 2013
• Start date: April 2008
• Est. completion date: January 2009

Study information

• Verified date: July 2013
• Source: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationGreat Britain: Medicines and Healthcare Products Regulatory AgencyUnited States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 451
• Est. completion date: January 2009
• Est. primary completion date: January 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Non Insulin Dependent
• Diabetes Mellitus, Type 2
• Diabetes Mellitus, Type II

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.
• Sitagliptin
One 100 mg over-encapsulated tablet orally (by mouth) once daily for 12 weeks.
• Placebo
One matching placebo capsule orally (by mouth) once or twice daily for 12 weeks.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Countries where clinical trial is conducted

United States,  Argentina,  Bulgaria,  Canada,  Czech Republic,  India,  Malaysia,  Mexico,  Poland,  Puerto Rico,  Romania,  Russian Federation,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in HbA1c From Baseline to 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.	Day 1 (Baseline) and Week 12	No
Secondary	Change in Fasting Plasma Glucose (FPG) From Baseline to 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.	Day 1 (Baseline) and Week 12	No
Secondary	Percentage of Patients With Symptoms of Hypoglycemia	The table below shows the percentage of patients who experienced symptomatic hypoglycemic events between Baseline and Week 12.	Up to Week 12	No
Secondary	Change in Overnight Urine Glucose/Creatinine Ratio From Baseline to 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.	Day 1 (Baseline) and Week 12	No
Secondary	Absolute Change in Body Weight From Baseline to Week 12	The table below shows the mean absolute change in body weight from Baseline to Week 12 for each treatment group.	Day 1 (Baseline) and Week 12	No
Secondary	Percent Change in Body Weight From Baseline to 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.	Day 1 (Baseline) and Week 12	No