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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier:
NCT00650806
First received: March 31, 2008
Last updated: April 1, 2013
Last verified: April 2013
  Purpose

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.


Condition Intervention Phase
Obesity
Drug: Canagliflozin (JNJ-28431754)
Drug: Placebo
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:

Primary Outcome Measures:
  • Percent Change in Body Weight From Baseline to Week 12 [ Time Frame: Day 1 (Baseline) and Week 12 ] [ Designated as safety issue: No ]
    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 group minus placebo) in the least-squares mean percent change.


Secondary Outcome Measures:
  • Absolute Change in Body Weight From Baseline to Week 12 [ Time Frame: Day 1 (Baseline) and Week 12 ] [ Designated as safety issue: No ]
    The table below shows the mean absolute change in body weight from Baseline to Week 12 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the least-squares mean change.

  • Change in Body Mass Index (BMI) From Baseline to Week 12 [ Time Frame: Day 1 (Baseline) and Week 12 ] [ Designated as safety issue: No ]
    The table below shows the mean change in BMI from Baseline to Week 12 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the least-squares mean change.

  • Percentage of Patients Who Lost at Least 5% of Their Initial Body Weight by Week 12 [ Time Frame: Day 1 (Baseline) and Week 12 ] [ Designated as safety issue: No ]
    The table below shows the percentage of patients who lost at least 5% of their initial body weight by Week 12 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo).

  • Percentage of Patients Who Lost at Least 10% of Their Initial Body Weight by Week 12 [ Time Frame: Day 1 (Baseline) and Week 12 ] [ Designated as safety issue: No ]
    The table below shows the percentage of patients who lost at least 10% of their initial body weight by Week 12 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo).

  • Change in Waist Circumference From Baseline to Week 12 [ Time Frame: Day 1 (Baseline) and Week 12 ] [ Designated as safety issue: No ]
    The table below shows the mean change in waist circumference from Baseline to Week 12 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the least-squares mean change.

  • Change in Hip Circumference From Baseline to Week 12 [ Time Frame: Day 1 (Baseline) and Week 12 ] [ Designated as safety issue: No ]
    The table below shows the mean change in hip circumference from Baseline to Week 12 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the least-squares mean change.

  • Change in Waist/Hip Ratio From Baseline to Week 12 [ Time Frame: Day 1 (Baseline) and Week 12 ] [ Designated as safety issue: No ]
    The table below shows the mean change in waist/hip ratio from Baseline to Week 12 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the least-squares mean change.


Enrollment: 376
Study Start Date: May 2008
Study Completion Date: September 2008
Primary Completion Date: September 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Canagliflozin 50 mg
Each patient will receive 50 mg of canagliflozin (JNJ-28431754) once daily for 12 weeks.
Drug: Canagliflozin (JNJ-28431754)
One 50 mg, 100 mg, or 300 mg over-encapsulated tablet orally (by mouth) once daily for 12 weeks.
Experimental: Canagliflozin 100 mg
Each patient will receive 100 mg of canagliflozin (JNJ-28431754) once daily for 12 weeks.
Drug: Canagliflozin (JNJ-28431754)
One 50 mg, 100 mg, or 300 mg over-encapsulated tablet orally (by mouth) once daily for 12 weeks.
Experimental: Canagliflozin 300 mg
Each patient will receive 300 mg of canagliflozin (JNJ-28431754) once daily for 12 weeks.
Drug: Canagliflozin (JNJ-28431754)
One 50 mg, 100 mg, or 300 mg over-encapsulated tablet orally (by mouth) once daily for 12 weeks.
Placebo Comparator: Placebo
Each patient will receive matching placebo once daily for 12 weeks.
Drug: Placebo
One matching placebo capsule orally once daily for 12 weeks.

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

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00650806

  Show 36 Study Locations
Sponsors and Collaborators
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Investigators
Study Director: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
  More Information

No publications provided

Responsible Party: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier: NCT00650806     History of Changes
Other Study ID Numbers: CR014578, 28431754OBE2001
Study First Received: March 31, 2008
Results First Received: April 1, 2013
Last Updated: April 1, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:
Obesity
Overweight
Weight loss
Anti-Obesity Agents
Human

Additional relevant MeSH terms:
Obesity
Overweight
Overnutrition
Nutrition Disorders
Body Weight
Signs and Symptoms
Anti-Obesity Agents
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 22, 2014