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

Johnson & Johnson (J&J)

Status and phase: Completed; Phase 2

Conditions: Diabetes Mellitus, Type II; Diabetes Mellitus, Non Insulin Dependent

Treatments: Drug: Placebo; Drug: Canagliflozin (JNJ-28431754); Drug: Sitagliptin

Study type: Interventional

Funder types: Industry

Identifiers

NCT00642278

28431754DIA2001 (Other Identifier)

CR014587

Details and patient eligibility

About

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.

Full 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).

Enrollment: 451 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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451 participants in 7 patient groups, including a placebo group

Canagliflozin 50 mg daily

Experimental group

Description:

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).

Treatment:

Drug: Canagliflozin (JNJ-28431754)

Drug: Placebo

Canagliflozin 100 mg daily

Experimental group

Description:

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).

Treatment:

Drug: Canagliflozin (JNJ-28431754)

Drug: Placebo

Canagliflozin 200 mg daily

Experimental group

Description:

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).

Treatment:

Drug: Canagliflozin (JNJ-28431754)

Drug: Placebo

Canagliflozin 300 mg daily

Experimental group

Description:

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).

Treatment:

Drug: Canagliflozin (JNJ-28431754)

Drug: Placebo

Canagliflozin 300 mg twice daily

Experimental group

Description:

Each patient will receive 300 mg of canagliflozin (JNJ-28431754) twice daily for 12 weeks.

Treatment:

Drug: Canagliflozin (JNJ-28431754)

Sitagliptin 100 mg daily

Active Comparator group

Description:

Each patient will receive 100 mg of sitagliptin once daily (in the morning) for 12 weeks with matching placebo once daily (in the evening).

Treatment:

Drug: Placebo

Drug: Sitagliptin

Placebo

Placebo Comparator group

Description:

Each patient will receive matching placebo twice daily for 12 weeks.

Treatment:

Drug: Placebo