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

NCT ID: NCT00642278

Last Updated: 2013-07-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 451 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-04-30
• Study Completion Date: 2009-01-31

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).

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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).

Group Type: EXPERIMENTAL

Canagliflozin (JNJ-28431754)

Intervention Type: DRUG

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.

Placebo

Intervention Type: DRUG

One matching placebo capsule orally (by mouth) once or twice daily for 12 weeks.

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).

Group Type: EXPERIMENTAL

Canagliflozin (JNJ-28431754)

Intervention Type: DRUG

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.

Placebo

Intervention Type: DRUG

One matching placebo capsule orally (by mouth) once or twice daily for 12 weeks.

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).

Group Type: EXPERIMENTAL

Canagliflozin (JNJ-28431754)

Intervention Type: DRUG

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.

Placebo

Intervention Type: DRUG

One matching placebo capsule orally (by mouth) once or twice daily for 12 weeks.

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).

Group Type: EXPERIMENTAL

Canagliflozin (JNJ-28431754)

Intervention Type: DRUG

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.

Placebo

Intervention Type: DRUG

One matching placebo capsule orally (by mouth) once or twice daily for 12 weeks.

Canagliflozin 300 mg twice daily

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

Group Type: EXPERIMENTAL

Canagliflozin (JNJ-28431754)

Intervention Type: DRUG

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 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).

Group Type: ACTIVE_COMPARATOR

Sitagliptin

Intervention Type: DRUG

One 100 mg over-encapsulated tablet orally (by mouth) once daily for 12 weeks.

Placebo

Intervention Type: DRUG

One matching placebo capsule orally (by mouth) once or twice daily for 12 weeks.

Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

One matching placebo capsule orally (by mouth) once or twice daily for 12 weeks.

Interventions

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.

Intervention Type: DRUG

Sitagliptin

One 100 mg over-encapsulated tablet orally (by mouth) once daily for 12 weeks.

Intervention Type: DRUG

Placebo

One matching placebo capsule orally (by mouth) once or twice daily for 12 weeks.

Intervention Type: DRUG

Other Intervention Names

JNJ-28431754

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial

Role: STUDY_DIRECTOR

Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Locations

Birmingham, Alabama, United States

Mesa, Arizona, United States

Tucson, Arizona, United States

Encinitas, California, United States

Lincoln, California, United States

Los Angeles, California, United States

Merced, California, United States

Roseville, California, United States

Denver, Colorado, United States

Golden, Colorado, United States

Hollywood, Florida, United States

Jacksonville, Florida, United States

Boise, Idaho, United States

Nampa, Idaho, United States

Topeka, Kansas, United States

Haverhill, Massachusetts, United States

Cherry Hill, New Jersey, United States

Albuquerque, New Mexico, United States

New Hyde Park, New York, United States

Salisbury, North Carolina, United States

Oklahoma City, Oklahoma, United States

Tulsa, Oklahoma, United States

Portland, Oregon, United States

Greer, South Carolina, United States

Dallas, Texas, United States

Houston, Texas, United States

New Braunfels, Texas, United States

Odessa, Texas, United States

San Antonio, Texas, United States

Milwaukee, Wisconsin, United States

Buenos Aires, , Argentina

Bueos Aires, , Argentina

Pleven, , Bulgaria

Sofia, , Bulgaria

Chilliwack, British Columbia, Canada

Coquitlam, British Columbia, Canada

Brampton, Ontario, Canada

Sarnia, Ontario, Canada

Toronto, Ontario, Canada

Pointe-Claire, Quebec, Canada

Saint Romuald, Quebec, Canada

Saskatoon, Saskatchewan, Canada

Olomouc, , Czechia

Písek, , Czechia

Prague, , Czechia

Bangalore, , India

Hyderabad, , India

Nagpur, , India

Pune, , India

Kota Bharu, , Malaysia

Kuala Lumpur, , Malaysia

Mexico City, , Mexico

México, , Mexico

Monterrey, , Mexico

Zapopan, , Mexico

Bydgoszcz, , Poland

Gdansk, , Poland

Kutno, , Poland

Lodz, , Poland

Lublin, , Poland

Torun, , Poland

Warsaw, , Poland

Wroclaw, , Poland

Ponce Pr, , Puerto Rico

San Juan, , Puerto Rico

Baia Mare, , Romania

Brasov, , Romania

Bucharest, , Romania

Cluj-Napoca, , Romania

Galati, , Romania

Ploieşti, , Romania

Moscow, , Russia

Saint Petersburg, , Russia

Samara, , Russia

Belfast, , United Kingdom

Bolton, , United Kingdom

Exeter, , United Kingdom

Lincoln, , United Kingdom

Countries

United States; Argentina; Bulgaria; Canada; Czechia; India; Malaysia; Mexico; Poland; Puerto Rico; Romania; Russia; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 22632452 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 22548646 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 22492586 (View on PubMed)

Other Identifiers

28431754DIA2001

Identifier Type: OTHER

Identifier Source: secondary_id

CR014587

Identifier Type: -

Identifier Source: org_study_id