Obesity
Conditions
Keywords
Obesity, Overweight, Weight loss, Anti-Obesity Agents, Human
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.
Interventions
One 50 mg, 100 mg, or 300 mg over-encapsulated tablet orally (by mouth) once daily for 12 weeks.
DRUGPlacebo
One matching placebo capsule orally once daily for 12 weeks.
Sponsors
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Body Weight From Baseline to Week 12 | Day 1 (Baseline) and Week 12 | 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
| Measure | Time frame | Description |
|---|---|---|
| Change in Body Mass Index (BMI) From Baseline to Week 12 | Day 1 (Baseline) and Week 12 | 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 | Day 1 (Baseline) and Week 12 | 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 | Day 1 (Baseline) and Week 12 | 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). |
| Absolute Change in Body Weight From Baseline to Week 12 | Day 1 (Baseline) and Week 12 | 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 Hip Circumference From Baseline to Week 12 | Day 1 (Baseline) and Week 12 | 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 | Day 1 (Baseline) and Week 12 | 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. |
| Change in Waist Circumference From Baseline to Week 12 | Day 1 (Baseline) and Week 12 | 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. |
Countries
Puerto Rico, United States
Participant flow
Recruitment details
This study evaluated the efficacy and safety of canagliflozin (JNJ-28431754) in nondiabetic, overweight, and obese patients. The study was conducted between 31 March 2008 and 18 September 2008 and recruited patients from 38 study centers located in the United States and Puerto Rico.
Pre-assignment details
A total of 376 patients were randomly allocated to the 4 treatment arms in the study and comprised the intent-to-treat analysis set which was used for the efficacy analyses. All 376 patients received at least 1 dose of study drug and were included in the safety analysis set.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Each patient received matching placebo once daily for 12 weeks. | 89 |
| Canagliflozin 50 mg Each patient received 50 mg of canagliflozin (JNJ-28431754) once daily for 12 weeks. | 98 |
| Canagliflozin 100 mg Each patient received 100 mg of canagliflozin (JNJ-28431754) once daily for 12 weeks. | 93 |
| Canagliflozin 300 mg Each patient received 300 mg of canagliflozin (JNJ-28431754) once daily for 12 weeks. | 96 |
| Total | 376 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 5 | 3 | 4 |
| Overall Study | Lost to Follow-up | 7 | 6 | 11 | 10 |
| Overall Study | Noncompliance with study drug regimen | 1 | 1 | 0 | 0 |
| Overall Study | Other | 1 | 1 | 2 | 0 |
| Overall Study | Pregnancy | 0 | 0 | 0 | 1 |
| Overall Study | Protocol Violation | 0 | 0 | 0 | 1 |
| Overall Study | Study terminated by sponsor | 2 | 3 | 5 | 4 |
| Overall Study | Withdrawal by Subject | 7 | 5 | 8 | 6 |
Baseline characteristics
| Characteristic | Placebo | Canagliflozin 50 mg | Canagliflozin 100 mg | Canagliflozin 300 mg | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 1 Participants | 0 Participants | 2 Participants | 4 Participants |
| Age, Categorical Between 18 and 65 years | 88 Participants | 97 Participants | 93 Participants | 94 Participants | 372 Participants |
| Age Continuous | 45.1 years STANDARD_DEVIATION 11.92 | 44.9 years STANDARD_DEVIATION 11.8 | 45.8 years STANDARD_DEVIATION 10.95 | 43.5 years STANDARD_DEVIATION 10.99 | 44.8 years STANDARD_DEVIATION 11.4 |
| Region Enroll PUERTO RICO | 3 participants | 4 participants | 4 participants | 5 participants | 16 participants |
| Region Enroll UNITED STATES | 86 participants | 94 participants | 89 participants | 91 participants | 360 participants |
| Sex: Female, Male Female | 75 Participants | 86 Participants | 76 Participants | 86 Participants | 323 Participants |
| Sex: Female, Male Male | 14 Participants | 12 Participants | 17 Participants | 10 Participants | 53 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 28 / 89 | 41 / 98 | 30 / 93 | 31 / 96 |
| serious Total, serious adverse events | 0 / 89 | 1 / 98 | 0 / 93 | 0 / 96 |
Outcome results
Primary
Percent Change in Body Weight From Baseline to Week 12
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.
Time frame: Day 1 (Baseline) and Week 12
Population: This analysis was conducted using the intent-to-treat analysis set, which included all patients who were randomly assigned to a treatment group. The last-observation-carried-forward method was applied when the Week 12 values were missing. The table includes only patients with both baseline and post baseline values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change in Body Weight From Baseline to Week 12 | -1.1 Percent change | Standard Deviation 2.4 |
| Canagliflozin 50 mg | Percent Change in Body Weight From Baseline to Week 12 | -2.0 Percent change | Standard Deviation 3 |
| Canagliflozin 100 mg | Percent Change in Body Weight From Baseline to Week 12 | -2.8 Percent change | Standard Deviation 2.9 |
| Canaglifloziin 300 mg | Percent Change in Body Weight From Baseline to Week 12 | -2.5 Percent change | Standard Deviation 3 |
p-value: 0.03195% CI: [-1.6, -0.1]ANOVA
p-value: <0.00195% CI: [-2.4, -0.8]ANOVA
p-value: <0.00195% CI: [-2.1, -0.6]ANOVA
Secondary
Absolute Change in Body Weight From Baseline to Week 12
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.
Time frame: Day 1 (Baseline) and Week 12
Population: This analysis was conducted using the intent-to-treat analysis set, which included all patients who were randomly assigned to a treatment group. The last-observation-carried-forward method was applied when the Week 12 values were missing. The table includes only patients with both baseline and post baseline values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Absolute Change in Body Weight From Baseline to Week 12 | -1.1 kg | Standard Deviation 2.46 |
| Canagliflozin 50 mg | Absolute Change in Body Weight From Baseline to Week 12 | -1.9 kg | Standard Deviation 2.9 |
| Canagliflozin 100 mg | Absolute Change in Body Weight From Baseline to Week 12 | -2.8 kg | Standard Deviation 2.9 |
| Canaglifloziin 300 mg | Absolute Change in Body Weight From Baseline to Week 12 | -2.4 kg | Standard Deviation 2.9 |
p-value: 0.04595% CI: [-1.58, -0.02]ANCOVA
p-value: <0.00195% CI: [-2.4, -0.8]ANCOVA
p-value: 0.00195% CI: [-2.07, -0.51]ANCOVA
Secondary
Change in Body Mass Index (BMI) From Baseline to Week 12
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.
Time frame: Day 1 (Baseline) and Week 12
Population: This analysis was conducted using the intent-to-treat analysis set, which included all patients who were randomly assigned to a treatment group. The last-observation-carried-forward method was applied when the Week 12 values were missing. The table includes only patients with both baseline and post baseline values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Body Mass Index (BMI) From Baseline to Week 12 | -0.4 kg/m2 | Standard Deviation 0.86 |
| Canagliflozin 50 mg | Change in Body Mass Index (BMI) From Baseline to Week 12 | -0.7 kg/m2 | Standard Deviation 1.05 |
| Canagliflozin 100 mg | Change in Body Mass Index (BMI) From Baseline to Week 12 | -1.0 kg/m2 | Standard Deviation 1.05 |
| Canaglifloziin 300 mg | Change in Body Mass Index (BMI) From Baseline to Week 12 | -0.9 kg/m2 | Standard Deviation 1.07 |
p-value: 0.03195% CI: [-0.59, -0.03]ANCOVA
p-value: <0.00195% CI: [-0.9, -0.32]ANCOVA
p-value: <0.00195% CI: [-0.76, -0.2]ANCOVA
Secondary
Change in Hip Circumference From Baseline to Week 12
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.
Time frame: Day 1 (Baseline) and Week 12
Population: This analysis was conducted using the intent-to-treat analysis set, which included all patients who were randomly assigned to a treatment group. The last-observation-carried-forward method was applied when the Week 12 values were missing. The table includes only patients with both baseline and post baseline values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Hip Circumference From Baseline to Week 12 | 0.1 cm | Standard Deviation 10.38 |
| Canagliflozin 50 mg | Change in Hip Circumference From Baseline to Week 12 | -2.0 cm | Standard Deviation 3.97 |
| Canagliflozin 100 mg | Change in Hip Circumference From Baseline to Week 12 | -2.1 cm | Standard Deviation 10.62 |
| Canaglifloziin 300 mg | Change in Hip Circumference From Baseline to Week 12 | -3.0 cm | Standard Deviation 7.95 |
p-value: 0.14995% CI: [-3.85, 0.59]ANCOVA
p-value: 0.54195% CI: [-3.05, 1.6]ANCOVA
p-value: 0.12195% CI: [-4.03, 0.47]ANCOVA
Secondary
Change in Waist Circumference From Baseline to Week 12
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.
Time frame: Day 1 (Baseline) and Week 12
Population: This analysis was conducted using the intent-to-treat analysis set, which included all patients who were randomly assigned to a treatment group. The last-observation-carried-forward method was applied when the Week 12 values were missing. The table includes only patients with both baseline and post baseline values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Waist Circumference From Baseline to Week 12 | -1.2 cm | Standard Deviation 10.06 |
| Canagliflozin 50 mg | Change in Waist Circumference From Baseline to Week 12 | -1.4 cm | Standard Deviation 4.99 |
| Canagliflozin 100 mg | Change in Waist Circumference From Baseline to Week 12 | -2.9 cm | Standard Deviation 10.32 |
| Canaglifloziin 300 mg | Change in Waist Circumference From Baseline to Week 12 | -2.6 cm | Standard Deviation 7.22 |
p-value: 0.83595% CI: [-2.68, 2.17]ANCOVA
p-value: 0.46695% CI: [-3.47, 1.59]ANCOVA
p-value: 0.27395% CI: [-3.87, 1.09]ANCOVA
Secondary
Change in Waist/Hip Ratio From Baseline to Week 12
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.
Time frame: Day 1 (Baseline) and Week 12
Population: This analysis was conducted using the intent-to-treat analysis set, which included all patients who were randomly assigned to a treatment group. The last-observation-carried-forward method was applied when the Week 12 values were missing. The table includes only patients with both baseline and post baseline values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Waist/Hip Ratio From Baseline to Week 12 | -0.011 ratio | Standard Deviation 0.0542 |
| Canagliflozin 50 mg | Change in Waist/Hip Ratio From Baseline to Week 12 | 0.003 ratio | Standard Deviation 0.0422 |
| Canagliflozin 100 mg | Change in Waist/Hip Ratio From Baseline to Week 12 | -0.008 ratio | Standard Deviation 0.0915 |
| Canaglifloziin 300 mg | Change in Waist/Hip Ratio From Baseline to Week 12 | -0.004 ratio | Standard Deviation 0.0469 |
p-value: 0.23995% CI: [-0.0071, 0.0286]ANCOVA
p-value: 0.995% CI: [-0.0174, 0.0198]ANCOVA
p-value: 0.82295% CI: [-0.016, 0.0202]ANCOVA
Secondary
Percentage of Patients Who Lost at Least 10% of Their Initial Body Weight by Week 12
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).
Time frame: Day 1 (Baseline) and Week 12
Population: This analysis was conducted using the intent-to-treat analysis set, which included all patients who were randomly assigned to a treatment group. The last-observation-carried-forward method was applied when the Week 12 values were missing. The table includes only patients with both baseline and post baseline values.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Patients Who Lost at Least 10% of Their Initial Body Weight by Week 12 | 0.0 Percentage of patients |
| Canagliflozin 50 mg | Percentage of Patients Who Lost at Least 10% of Their Initial Body Weight by Week 12 | 3.2 Percentage of patients |
| Canagliflozin 100 mg | Percentage of Patients Who Lost at Least 10% of Their Initial Body Weight by Week 12 | 2.4 Percentage of patients |
| Canaglifloziin 300 mg | Percentage of Patients Who Lost at Least 10% of Their Initial Body Weight by Week 12 | 1.1 Percentage of patients |
p-value: 0.117Cochran-Mantel-Haenszel
p-value: 0.225Cochran-Mantel-Haenszel
p-value: 0.317Cochran-Mantel-Haenszel
Secondary
Percentage of Patients Who Lost at Least 5% of Their Initial Body Weight by Week 12
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).
Time frame: Day 1 (Baseline) and Week 12
Population: This analysis was conducted using the intent-to-treat analysis set, which included all patients who were randomly assigned to a treatment group. The last-observation-carried-forward method was applied when the Week 12 values were missing. The table includes only patients with both baseline and post baseline values.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Patients Who Lost at Least 5% of Their Initial Body Weight by Week 12 | 8.1 Percentage of patients |
| Canagliflozin 50 mg | Percentage of Patients Who Lost at Least 5% of Their Initial Body Weight by Week 12 | 12.6 Percentage of patients |
| Canagliflozin 100 mg | Percentage of Patients Who Lost at Least 5% of Their Initial Body Weight by Week 12 | 18.8 Percentage of patients |
| Canaglifloziin 300 mg | Percentage of Patients Who Lost at Least 5% of Their Initial Body Weight by Week 12 | 17.2 Percentage of patients |
p-value: 0.31795% CI: [0.6, 5.6]Cochran-Mantel-Haenszel
p-value: 0.05995% CI: [0.9, 11.1]Cochran-Mantel-Haenszel
p-value: 0.02795% CI: [1, 10]Cochran-Mantel-Haenszel