Clinical trial NCT00642278: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diabetes Mellitus, Type II
Diabetes Mellitus, Non Insulin Dependent
Keywords: Type 2 diabetes mellitus
Metformin
Hemoglobin A1c
Lead sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Sponsor class: INDUSTRY
First posted: 2008-03-25
Enrollment: 451
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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

Primary outcomes:
measure: Change in HbA1c From Baseline to Week 12
timeFrame: Day 1 (Baseline) and Week 12
Secondary outcomes:
measure: Change in Fasting Plasma Glucose (FPG) From Baseline to Week 12
timeFrame: Day 1 (Baseline) and Week 12
measure: Percentage of Patients With Symptoms of Hypoglycemia
timeFrame: Up to Week 12
measure: Change in Overnight Urine Glucose/Creatinine Ratio From Baseline to Week 12
timeFrame: Day 1 (Baseline) and Week 12
measure: Absolute Change in Body Weight From Baseline to Week 12
timeFrame: Day 1 (Baseline) and Week 12
measure: Percent Change in Body Weight From Baseline to Week 12
timeFrame: Day 1 (Baseline) and Week 12
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Mesa
country: United States
state: Arizona
city: Tucson
country: United States
state: Arizona
city: Encinitas
country: United States
state: California
city: Lincoln
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Merced
country: United States
state: California
city: Roseville
country: United States
state: California
city: Denver
country: United States
state: Colorado
city: Golden
country: United States
state: Colorado
city: Hollywood
country: United States
state: Florida
city: Jacksonville
country: United States
state: Florida
city: Boise
country: United States
state: Idaho
city: Nampa
country: United States
state: Idaho
city: Topeka
country: United States
state: Kansas
city: Haverhill
country: United States
state: Massachusetts
city: Cherry Hill
country: United States
state: New Jersey
city: Albuquerque
country: United States
state: New Mexico
city: New Hyde Park
country: United States
state: New York
city: Salisbury
country: United States
state: North Carolina
city: Oklahoma City
country: United States
state: Oklahoma
city: Tulsa
country: United States
state: Oklahoma
city: Portland
country: United States
state: Oregon
city: Greer
country: United States
state: South Carolina
city: Dallas
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: New Braunfels
country: United States
state: Texas
city: Odessa
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Milwaukee
country: United States
state: Wisconsin
city: Buenos Aires
country: Argentina
city: Bueos Aires
country: Argentina
city: Pleven
country: Bulgaria
city: Sofia N/A
country: Bulgaria
city: Sofia
country: Bulgaria
city: Chilliwack
country: Canada
state: British Columbia
city: Coquitlam
country: Canada
state: British Columbia
city: Brampton
country: Canada
state: Ontario
city: Sarnia
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Pointe-Claire
country: Canada
state: Quebec
city: St Romuald
country: Canada
state: Quebec
city: Saskatoon
country: Canada
state: Saskatchewan
city: Olomouc 9
country: Czech Republic
city: Pisek 1
country: Czech Republic
city: Praha 28
country: Czech Republic
city: Praha 5
country: Czech Republic
city: Praha
country: Czech Republic
city: Bangalore
country: India
city: Hyderabad
country: India
city: Nagpur
country: India
city: Pune
country: India
city: Kota Bharu
country: Malaysia
city: Kuala Lumpur N/A
country: Malaysia
city: Kuala Lumpur
country: Malaysia
city: Ciudad De Mexico
country: Mexico
city: Mexico
country: Mexico
city: Monterrey
country: Mexico
city: Zapopan
country: Mexico
city: Bydgoszcz
country: Poland
city: Gdansk
country: Poland
city: Kutno 001
country: Poland
city: Lodz
country: Poland
city: Lublin N/A
country: Poland
city: Torun
country: Poland
city: Warszawa
country: Poland
city: Wroclaw
country: Poland
city: Ponce Pr
country: Puerto Rico
city: San Juan
country: Puerto Rico
city: Baia Mare
country: Romania
city: Brasov
country: Romania
city: Bucharest
country: Romania
city: Cluj
country: Romania
city: Galati
country: Romania
city: Ploiesti
country: Romania
city: Moscow N/A
country: Russian Federation
city: Moscow
country: Russian Federation
city: Saint Petersburg
country: Russian Federation
city: Samara
country: Russian Federation
city: St Petersburg N/A
country: Russian Federation
city: St-Petersburg
country: Russian Federation
city: Belfast
country: United Kingdom
city: Bolton
country: United Kingdom
city: Exeter
country: United Kingdom
city: Lincoln
country: United Kingdom
Study officials:
affiliation: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
name: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.