Clinical trial NCT00650806: A Study of the Safety and Effectiveness of Canagliflozin (JNJ-28431754) in Promoting Weight Loss in Overweight and Obese Patients Who do Not Have Diabetes
Official title: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Dose-Ranging Study to Investigate the Safety and Efficacy of JNJ-28431754 in Nondiabetic Overweight and Obese Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Obesity
Keywords: Obesity
Overweight
Weight loss
Anti-Obesity Agents
Human
Lead sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Sponsor class: INDUSTRY
First posted: 2008-04-02
Enrollment: 376
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 test the safety and effectiveness of JNJ-28431754 in promoting weight loss in patients who are overweight or obese and who do not have diabetes.

Detailed description: The prevalence of obesity is increasing worldwide. Obesity and being overweight are major risk factors for chronic cardiovascular disease, type 2 diabetes mellitus, hypertension and stroke, and certain types of cancers. JNJ-28431754 is being investigated in this study for its possible effectiveness in promoting weight loss when taken over a 12-week period. The study consists of 3 phases: a pretreatment phase that includes a 7-day screening period and a 4-week run-in period, a 12-week double-blind treatment phase (neither the patient nor the investigator will know which treatment the patient is receiving) with an end-of-treatment visit, and a posttreatment phase. In the pretreatment phase, after giving written informed consent, patients will undergo screening evaluations. Patients who successfully complete the screening period will enter the 4-week run-in period and be given dietary and exercise counseling as standardized non-drug therapy for weight loss. During the 12 weeks of treatment, all patients will continue on the study diet and exercise non-drug therapy and will visit the study site about every 3 weeks to have their weight and the results of other safety and effectiveness tests recorded, and to have blood samples collected to measure the concentration of JNJ-28431754 in their blood. In the posttreatment phase, patients will return to the study site for a follow-up visit 14 days after receiving their last dose of study drug. Patient safety will be monitored throughout the study using spontaneous adverse event reporting, clinical laboratory tests (hematology, serum chemistry, urinalysis); pregnancy tests; physical examinations; electrocardiograms; vital signs measurements; overnight urine collection to measure albumin excretion; assessment of calcium and phosphate homeostasis (balance), bone formation and reabsorption markers, and hormones regulating calcium and phosphorus homeostasis; and self administered vaginal and urine sample collection for fungal and bacterial culture in subjects with symptoms consistent with vulvovaginal candidiasis and urinary tract infection. Patients will complete 2 questionnaires to record their reactions to taking the study drug and the effect of body weight on their daily lives. About 100 patients of the approximately 400 who qualify for the study, and who consent to this, will take part in 2 oral glucose tolerance tests (OGTTs). During the OGTTs they will drink a glucose solution and have a series of blood samples collected to measure glucose concentration, collect their urine over a 2 hour period, and (at the second OGTT only) have blood samples collected to measure JNJ 28431754 blood concentrations. The primary clinical theory for this study is that at well-tolerated doses, JNJ-28431754 is superior to placebo as measured by the percent change in body weight from baseline (Day 1 of the double-blind treatment period) through Week 12.

Eligibility criteria: Inclusion Criteria:

* BMI \>=30 kg/m2 and \<50 kg/m2 or a BMI \>=27 kg/m2 and \<50 kg/m2 in the presence of controlled hypertension and/or treated or untreated dyslipidemia
* Must have a stable weight, i.e., increasing or decreasing not more than 5% in the 3 months before screening
* Serum creatinine \<=1.5 mg/dL for men and \<=1.4 mg/dL for women at screening
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels within 2 times the upper limit of normal (ULN) and bilirubin within the normal range, unless the findings are consistent with Gilbert's disease
* fasting plasma glucose PG \<7.0 mmol/L (126 mg/dL) at screening

Exclusion Criteria:

* A history of hereditary glucose-galactose malabsorption or primary renal glycosuria
* An established diagnosis of diabetes mellitus or treatment with glucose lowering drugs at screening
* A history of reactive hypoglycemia or of symptomatology possibly due to hypoglycemia
* Fasting triglyceride level \>6.78 mmol/L (600 mg/dL) at screening
* History of obesity with a known cause (e.g., Cushing's disease)

Primary outcomes:
measure: Percent Change in Body Weight From Baseline to Week 12
timeFrame: Day 1 (Baseline) and Week 12
Secondary outcomes:
measure: Absolute Change in Body Weight From Baseline to Week 12
timeFrame: Day 1 (Baseline) and Week 12
measure: Change in Body Mass Index (BMI) From Baseline to Week 12
timeFrame: Day 1 (Baseline) and Week 12
measure: Percentage of Patients Who Lost at Least 5% of Their Initial Body Weight by Week 12
timeFrame: Day 1 (Baseline) and Week 12
measure: Percentage of Patients Who Lost at Least 10% of Their Initial Body Weight by Week 12
timeFrame: Day 1 (Baseline) and Week 12
measure: Change in Waist Circumference From Baseline to Week 12
timeFrame: Day 1 (Baseline) and Week 12
measure: Change in Hip Circumference From Baseline to Week 12
timeFrame: Day 1 (Baseline) and Week 12
measure: Change in Waist/Hip Ratio From Baseline to Week 12
timeFrame: Day 1 (Baseline) and Week 12
Other outcomes:
Locations:
city: Hot Springs
country: United States
state: Arkansas
city: Walnut Creek
country: United States
state: California
city: Westlake Village
country: United States
state: California
city: Destin
country: United States
state: Florida
city: Jacksonville
country: United States
state: Florida
city: Augusta
country: United States
state: Georgia
city: Decatur
country: United States
state: Georgia
city: Stockbridge
country: United States
state: Georgia
city: Boise
country: United States
state: Idaho
city: Eagle
country: United States
state: Idaho
city: Meridian
country: United States
state: Idaho
city: Evansville
country: United States
state: Indiana
city: Overland Park
country: United States
state: Kansas
city: Witchita
country: United States
state: Kansas
city: Lexington
country: United States
state: Kentucky
city: Louisville
country: United States
state: Kentucky
city: New Orleans
country: United States
state: Louisiana
city: Auburn
country: United States
state: Maine
city: Milford
country: United States
state: Massachusetts
city: Jackson
country: United States
state: Mississippi
city: Omaha
country: United States
state: Nebraska
city: Manilus
country: United States
state: New York
city: Medford
country: United States
state: Oregon
city: Portland
country: United States
state: Oregon
city: Goose Creek
country: United States
state: South Carolina
city: Mt Pleasant
country: United States
state: South Carolina
city: Knoxville
country: United States
state: Tennessee
city: Nashville
country: United States
state: Tennessee
city: Amarillo
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Odessa
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: West Jordan
country: United States
state: Utah
city: Norfolk
country: United States
state: Virginia
city: Wauwatosa
country: United States
state: Wisconsin
city: Ponce
country: Puerto Rico
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: