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
Sponsor
Johnson & Johnson Pharmaceutical Research & Development, L.L.C. (Industry)
Overall Status
Completed
CT.gov ID
NCT00650806
Collaborator
(none)
376
36
4
4
10.4
2.6
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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.
Study Design
Study Type:
Interventional
Actual Enrollment
:
376 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, 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
Study Start Date
:
May 1, 2008
Actual Primary Completion Date
:
Sep 1, 2008
Actual Study Completion Date
:
Sep 1, 2008
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| 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.
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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 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).
- 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.
- 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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 65 Years
Sexes Eligible for Study:
All
Accepts 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)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Hot Springs | Arkansas | United States | ||
| 2 | Walnut Creek | California | United States | ||
| 3 | Westlake Village | California | United States | ||
| 4 | Destin | Florida | United States | ||
| 5 | Jacksonville | Florida | United States | ||
| 6 | Augusta | Georgia | United States | ||
| 7 | Decatur | Georgia | United States | ||
| 8 | Stockbridge | Georgia | United States | ||
| 9 | Boise | Idaho | United States | ||
| 10 | Eagle | Idaho | United States | ||
| 11 | Meridian | Idaho | United States | ||
| 12 | Evansville | Indiana | United States | ||
| 13 | Overland Park | Kansas | United States | ||
| 14 | Witchita | Kansas | United States | ||
| 15 | Lexington | Kentucky | United States | ||
| 16 | Louisville | Kentucky | United States | ||
| 17 | New Orleans | Louisiana | United States | ||
| 18 | Auburn | Maine | United States | ||
| 19 | Milford | Massachusetts | United States | ||
| 20 | Jackson | Mississippi | United States | ||
| 21 | Omaha | Nebraska | United States | ||
| 22 | Manilus | New York | United States | ||
| 23 | Medford | Oregon | United States | ||
| 24 | Portland | Oregon | United States | ||
| 25 | Goose Creek | South Carolina | United States | ||
| 26 | Mt Pleasant | South Carolina | United States | ||
| 27 | Knoxville | Tennessee | United States | ||
| 28 | Nashville | Tennessee | United States | ||
| 29 | Amarillo | Texas | United States | ||
| 30 | Dallas | Texas | United States | ||
| 31 | Odessa | Texas | United States | ||
| 32 | San Antonio | Texas | United States | ||
| 33 | West Jordan | Utah | United States | ||
| 34 | Norfolk | Virginia | United States | ||
| 35 | Wauwatosa | Wisconsin | United States | ||
| 36 | Ponce | Puerto Rico |
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.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier:
NCT00650806
Other Study ID Numbers:
- CR014578
- 28431754OBE2001
First Posted:
Apr 2, 2008
Last Update Posted:
May 24, 2013
Last Verified:
Apr 1, 2013
Keywords provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Additional relevant MeSH terms:
Study Results
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 Detail | 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. |
| Arm/Group Title | Placebo | Canagliflozin 50 mg | Canagliflozin 100 mg | Canagliflozin 300 mg |
|---|---|---|---|---|
| Arm/Group Description | Each patient received matching placebo once daily for 12 weeks. | Each patient received 50 mg of canagliflozin (JNJ-28431754) once daily for 12 weeks. | Each patient received 100 mg of canagliflozin (JNJ-28431754) once daily for 12 weeks. | Each patient received 300 mg of canaliflozin (JNJ-28431754) once daily for 12 weeks. |
| Period Title: Overall Study | ||||
| STARTED | 89 | 98 | 93 | 96 |
| COMPLETED | 71 | 77 | 64 | 70 |
| NOT COMPLETED | 18 | 21 | 29 | 26 |
Baseline Characteristics
| Arm/Group Title | Placebo | Canagliflozin 50 mg | Canagliflozin 100 mg | Canagliflozin 300 mg | Total |
|---|---|---|---|---|---|
| Arm/Group Description | Each patient received matching placebo once daily for 12 weeks. | Each patient received 50 mg of canagliflozin (JNJ-28431754) once daily for 12 weeks. | Each patient received 100 mg of canagliflozin (JNJ-28431754) once daily for 12 weeks. | Each patient received 300 mg of canagliflozin (JNJ-28431754) once daily for 12 weeks. | Total of all reporting groups |
| Overall Participants | 89 | 98 | 93 | 96 | 376 |
| Age (Count of Participants) | |||||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
88
98.9%
|
97
99%
|
93
100%
|
94
97.9%
|
372
98.9%
|
| >=65 years |
1
1.1%
|
1
1%
|
0
0%
|
2
2.1%
|
4
1.1%
|
| Age (years) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [years] |
45.1
(11.92)
|
44.9
(11.8)
|
45.8
(10.95)
|
43.5
(10.99)
|
44.8
(11.4)
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
75
84.3%
|
86
87.8%
|
76
81.7%
|
86
89.6%
|
323
85.9%
|
| Male |
14
15.7%
|
12
12.2%
|
17
18.3%
|
10
10.4%
|
53
14.1%
|
| Region Enroll (participants) [Number] | |||||
| PUERTO RICO |
3
3.4%
|
4
4.1%
|
4
4.3%
|
5
5.2%
|
16
4.3%
|
| UNITED STATES |
86
96.6%
|
94
95.9%
|
89
95.7%
|
91
94.8%
|
360
95.7%
|
Outcome Measures
| Title | Percent Change in Body Weight From Baseline to Week 12 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Placebo | Canagliflozin 50 mg | Canagliflozin 100 mg | Canaglifloziin 300 mg |
|---|---|---|---|---|
| Arm/Group Description | Each patient received matching placebo once daily for 12 weeks. | Each patient received 50 mg of canagliflozin (JNJ-28431754) once daily for 12 weeks. | Each patient received 100 mg of canagliflozin (JNJ-28431754) once daily for 12 weeks. | Each patient received 300 mg of canagliflozin (JNJ-28431754) once daily for 12 weeks. |
| Measure Participants | 86 | 95 | 85 | 93 |
| Mean (Standard Deviation) [Percent change] |
-1.1
(2.4)
|
-2.0
(3.0)
|
-2.8
(2.9)
|
-2.5
(3.0)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Canagliflozin 50 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.031 |
| Comments | ||
| Method | ANOVA | |
| Comments | Cofactors were treatment, run-in weight loss stratum, and pooled center. | |
| Method of Estimation | Estimation Parameter | Least-Squares Mean Difference |
| Estimated Value | -0.9 | |
| Confidence Interval |
(2-Sided) 95% -1.6 to -0.1 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.4 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Canagliflozin 100 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | ANOVA | |
| Comments | Cofactors were treatment, run-in weight loss stratum, and pooled center. | |
| Method of Estimation | Estimation Parameter | Least-Squares Mean Difference |
| Estimated Value | -1.6 | |
| Confidence Interval |
(2-Sided) 95% -2.4 to -0.8 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.4 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Canaglifloziin 300 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | ANOVA | |
| Comments | Cofactors were treatment, run-in weight loss stratum, and pooled center. | |
| Method of Estimation | Estimation Parameter | Least-Squares Mean Difference |
| Estimated Value | -1.4 | |
| Confidence Interval |
(2-Sided) 95% -2.1 to -0.6 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.4 |
|
| Estimation Comments | ||
| Title | Absolute Change in Body Weight From Baseline to Week 12 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Placebo | Canagliflozin 50 mg | Canagliflozin 100 mg | Canagliflozin 300 mg |
|---|---|---|---|---|
| Arm/Group Description | Each patient received matching placebo once daily for 12 weeks. | Each patient received 50 mg of canagliflozin (JNJ-28431754) once daily for 12 weeks. | Each patient received 100 mg of canagliflozin (JNJ-28431754) once daily for 12 weeks. | Each patient received 300 mg of canagliflozin (JNJ-28431754) once daily for 12 weeks. |
| Measure Participants | 86 | 95 | 85 | 93 |
| Mean (Standard Deviation) [kg] |
-1.1
(2.46)
|
-1.9
(2.90)
|
-2.8
(2.90)
|
-2.4
(2.90)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Canagliflozin 50 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.045 |
| Comments | ||
| Method | ANCOVA | |
| Comments | Cofactors were treatment, run-in weight loss stratum, and pooled center. Baseline body weight was a covariate. | |
| Method of Estimation | Estimation Parameter | Least-Squares Mean Difference |
| Estimated Value | -0.8 | |
| Confidence Interval |
(2-Sided) 95% -1.58 to -0.02 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.4 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Canagliflozin 100 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | Cofactors were treatment, run-in weight loss stratum, and pooled center. Baseline body weight was a covariate. | |
| Method of Estimation | Estimation Parameter | Least-Squares Mean Difference |
| Estimated Value | -1.6 | |
| Confidence Interval |
(2-Sided) 95% -2.40 to -0.80 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.41 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Canaglifloziin 300 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | Cofactors were treatment, run-in weight loss stratum, and pooled center. Baseline body weight was a covariate. | |
| Method of Estimation | Estimation Parameter | Least-Squares Mean Difference |
| Estimated Value | -1.3 | |
| Confidence Interval |
(2-Sided) 95% -2.07 to -0.51 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.40 |
|
| Estimation Comments | ||
| Title | Change in Body Mass Index (BMI) From Baseline to Week 12 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Placebo | Canagliflozin 50 mg | Canagliflozin 100 mg | Canagliflozin 300 mg |
|---|---|---|---|---|
| Arm/Group Description | Each patient received matching placebo once daily for 12 weeks. | Each patient received 50 mg of canagliflozin (JNJ-28431754) once daily for 12 weeks. | Each patient received 100 mg of canagliflozin (JNJ-28431754) once daily for 12 weeks. | Each patient received 300 mg of canagliflozin (JNJ-28431754) once daily for 12 weeks. |
| Measure Participants | 86 | 95 | 85 | 93 |
| Mean (Standard Deviation) [kg/m2] |
-0.4
(0.86)
|
-0.7
(1.05)
|
-1.0
(1.05)
|
-0.9
(1.07)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Canagliflozin 50 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.031 |
| Comments | ||
| Method | ANCOVA | |
| Comments | Cofactors were treatment, run-in weight loss stratum, and pooled center. The corresponding baseline measurement was a covariate. | |
| Method of Estimation | Estimation Parameter | Least-Squares Mean Difference |
| Estimated Value | -0.31 | |
| Confidence Interval |
(2-Sided) 95% -0.59 to -0.03 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.14 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Canagliflozin 100 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | Cofactors were treatment, run-in weight loss stratum, and pooled center. The corresponding baseline measurement was a covariate. | |
| Method of Estimation | Estimation Parameter | Least-Squares Mean Difference |
| Estimated Value | -0.6 | |
| Confidence Interval |
(2-Sided) 95% -0.90 to -0.32 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.15 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Canaglifloziin 300 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | Cofactors were treatment, run-in weight loss stratum, and pooled center. The corresponding baseline measurement was a covariate. | |
| Method of Estimation | Estimation Parameter | Least-Squares Mean Difference |
| Estimated Value | -0.48 | |
| Confidence Interval |
(2-Sided) 95% -0.76 to -0.20 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.14 |
|
| Estimation Comments | ||
| Title | Percentage of Patients Who Lost at Least 5% of Their Initial Body Weight by Week 12 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Placebo | Canagliflozin 50 mg | Canagliflozin 100 mg | Canagliflozin 300 mg |
|---|---|---|---|---|
| Arm/Group Description | Each patient received matching placebo once daily for 12 weeks. | Each patient received 50 mg of canagliflozin (JNJ-28431754) once daily for 12 weeks. | Each patient received 100 mg of canagliflozin (JNJ-28431754) once daily for 12 weeks. | Each patient received 300 mg of canagliflozin (JNJ-28431754) once daily for 12 weeks. |
| Measure Participants | 86 | 95 | 85 | 93 |
| Number [Percentage of patients] |
8.1
|
12.6
|
18.8
|
17.2
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Canagliflozin 50 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.317 |
| Comments | P-value controlled for run-in weight loss stratum and pooled center. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.7 | |
| Confidence Interval |
() 95% 0.6 to 5.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Odds ratio and Confidence Interval controlled for run-in weight loss stratum and pooled center. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Canagliflozin 100 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.059 |
| Comments | P-value controlled for run-in weight loss stratum and pooled center. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 2.9 | |
| Confidence Interval |
(2-Sided) 95% 0.9 to 11.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Odds ratio and Confidence Interval controlled for run-in weight loss stratum and pooled center. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Canaglifloziin 300 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.027 |
| Comments | P-value controlled for run-in weight loss stratum and pooled center. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 3.1 | |
| Confidence Interval |
(2-Sided) 95% 1.0 to 10.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Odds ratio and Confidence Interval controlled for run-in weight loss stratum and pooled center. | |
| Title | Percentage of Patients Who Lost at Least 10% of Their Initial Body Weight by Week 12 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Placebo | Canagliflozin 50 mg | Canagliflozin 100 mg | Canagliflozin 300 mg |
|---|---|---|---|---|
| Arm/Group Description | Each patient received matching placebo once daily for 12 weeks. | Each patient received 50 mg of canagliflozin (JNJ-28431754) once daily for 12 weeks. | Each patient received 100 mg of canagliflozin (JNJ-28431754) once daily for 12 weeks. | Each patient received 300 mg of canagliflozin (JNJ-28431754) once daily for 12 weeks. |
| Measure Participants | 86 | 95 | 85 | 93 |
| Number [Percentage of patients] |
0.0
|
3.2
|
2.4
|
1.1
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Canagliflozin 50 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.117 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test controlled for run-in weight loss stratum and pooled center. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Canagliflozin 100 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.225 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test controlled for run-in weight loss stratum and pooled center. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Canaglifloziin 300 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.317 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test controlled for run-in weight loss stratum and pooled center. | |
| Title | Change in Waist Circumference From Baseline to Week 12 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Placebo | Canagliflozin 50 mg | Canagliflozin 100 mg | Canagliflozin 300 mg |
|---|---|---|---|---|
| Arm/Group Description | Each patient received matching placebo once daily for 12 weeks. | Each patient received 50 mg of canagliflozin (JNJ-28431754) once daily for 12 weeks. | Each patient received 100 mg of canagliflozin (JNJ-28431754) once daily for 12 weeks. | Each patient received 300 mg of canagliflozin (JNJ-28431754) once daily for 12 weeks. |
| Measure Participants | 78 | 87 | 73 | 82 |
| Mean (Standard Deviation) [cm] |
-1.2
(10.06)
|
-1.4
(4.99)
|
-2.9
(10.32)
|
-2.6
(7.22)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Canagliflozin 50 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.835 |
| Comments | ||
| Method | ANCOVA | |
| Comments | Cofactors were treatment, run-in weight loss stratum, and pooled center. The corresponding baseline measurement was a covariate. | |
| Method of Estimation | Estimation Parameter | Least-Squares Mean Difference |
| Estimated Value | -0.26 | |
| Confidence Interval |
(2-Sided) 95% -2.68 to 2.17 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.23 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Canagliflozin 100 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.466 |
| Comments | ||
| Method | ANCOVA | |
| Comments | Cofactors were treatment, run-in weight loss stratum, and pooled center. The corresponding baseline measurement was a covariate. | |
| Method of Estimation | Estimation Parameter | Least-Squares Mean Difference |
| Estimated Value | -0.94 | |
| Confidence Interval |
(2-Sided) 95% -3.47 to 1.59 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.29 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Canaglifloziin 300 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.273 |
| Comments | ||
| Method | ANCOVA | |
| Comments | Cofactors were treatment, run-in weight loss stratum, and pooled center. The corresponding baseline measurement was a covariate. | |
| Method of Estimation | Estimation Parameter | Least-Sqaures Mean Difference |
| Estimated Value | -1.37 | |
| Confidence Interval |
(2-Sided) 95% -3.87 to 1.09 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.25 |
|
| Estimation Comments | ||
| Title | Change in Hip Circumference From Baseline to Week 12 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Placebo | Canaglifozin 50 mg | Canagliflozin 100 mg | Canagliflozin 300 mg |
|---|---|---|---|---|
| Arm/Group Description | Each patient received matching placebo once daily for 12 weeks. | Each patient received 50 mg of canagliflozin (JNJ-28431754) once daily for 12 weeks. | Each patient received 100 mg of canagliflozin (JNJ-28431754) once daily for 12 weeks. | Each patient received 300 mg of canagliflozin (JNJ-28431754) once daily for 12 weeks. |
| Measure Participants | 77 | 86 | 72 | 81 |
| Mean (Standard Deviation) [cm] |
0.1
(10.38)
|
-2.0
(3.97)
|
-2.1
(10.62)
|
-3.0
(7.95)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Canagliflozin 50 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.149 |
| Comments | ||
| Method | ANCOVA | |
| Comments | Cofactors were treatment, run-in weight loss stratum, and pooled center. The corresponding baseline measurement was a covariate. | |
| Method of Estimation | Estimation Parameter | Least-Squares Mean Difference |
| Estimated Value | -1.63 | |
| Confidence Interval |
(2-Sided) 95% -3.85 to 0.59 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.13 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Canagliflozin 100 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.541 |
| Comments | ||
| Method | ANCOVA | |
| Comments | Cofactors were treatment, run-in weight loss stratum, and pooled center. The corresponding baseline measurement was a covariate. | |
| Method of Estimation | Estimation Parameter | Least-Squares Mean Difference |
| Estimated Value | -0.72 | |
| Confidence Interval |
(2-Sided) 95% -3.05 to 1.6 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.18 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Canaglifloziin 300 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.121 |
| Comments | ||
| Method | ANCOVA | |
| Comments | Cofactors were treatment, run-in weight loss stratum, and pooled center. The corresponding baseline measurement was a covariate. | |
| Method of Estimation | Estimation Parameter | Least-Squares Mean Difference |
| Estimated Value | -1.78 | |
| Confidence Interval |
(2-Sided) 95% -4.03 to 0.47 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.15 |
|
| Estimation Comments | ||
| Title | Change in Waist/Hip Ratio From Baseline to Week 12 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Placebo | Canaglifozin 50 mg | Canagliflozin 100 mg | Canagliflozin 300 mg |
|---|---|---|---|---|
| Arm/Group Description | Each patient received matching placebo once daily for 12 weeks. | Each patient received 50 mg of canagliflozin (JNJ-28431754) once daily for 12 weeks. | Each patient received 100 mg of canagliflozin (JNJ-28431754) once daily for 12 weeks. | Each patient received 300 mg of canagliflozin (JNJ-28431754) once daily for 12 weeks. |
| Measure Participants | 77 | 86 | 72 | 81 |
| Mean (Standard Deviation) [ratio] |
-0.011
(0.0542)
|
0.003
(0.0422)
|
-0.008
(0.0915)
|
-0.004
(0.0469)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Canagliflozin 50 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.239 |
| Comments | ||
| Method | ANCOVA | |
| Comments | Cofactors were treatment, run-in weight loss stratum, and pooled center. The corresponding baseline measurement was a covariate. | |
| Method of Estimation | Estimation Parameter | Least-Squares Mean Difference |
| Estimated Value | 0.011 | |
| Confidence Interval |
(2-Sided) 95% -0.0071 to 0.0286 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0091 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Canagliflozin 100 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.900 |
| Comments | ||
| Method | ANCOVA | |
| Comments | Cofactors were treatment, run-in weight loss stratum, and pooled center. The corresponding baseline measurement was a covariate. | |
| Method of Estimation | Estimation Parameter | Least-Squares Mean Difference |
| Estimated Value | 0.001 | |
| Confidence Interval |
(2-Sided) 95% -0.0174 to 0.0198 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0095 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Canaglifloziin 300 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.822 |
| Comments | ||
| Method | ANCOVA | |
| Comments | Cofactors were treatment, run-in weight loss stratum, and pooled center. The corresponding baseline measurement was a covariate. | |
| Method of Estimation | Estimation Parameter | Least-Squares Mean Difference |
| Estimated Value | 0.002 | |
| Confidence Interval |
(2-Sided) 95% -0.0160 to 0.0202 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0092 |
|
| Estimation Comments | ||
Adverse Events
| Time Frame | Adverse events were reported for the duration of the study; each patient participated in the study for approximately 12 weeks. | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm. | |||||||
| Arm/Group Title | Placebo | Canagliflozin 50 mg | Canagliflozin 100 mg | Canagliflozin 300 mg | ||||
| Arm/Group Description | Each patient received matching placebo once daily for 12 weeks. | Each patient received 50 mg of canagliflozin (JNJ-28431754) once daily for 12 weeks. | Each patient received 100 mg of canagliflozin (JNJ-28431754) once daily for 12 weeks. | Each patient received 300 mg of canagliflozin (JNJ-28431754) once daily for 12 weeks. | ||||
All Cause Mortality |
||||||||
| Placebo | Canagliflozin 50 mg | Canagliflozin 100 mg | Canagliflozin 300 mg | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||
Serious Adverse Events |
||||||||
| Placebo | Canagliflozin 50 mg | Canagliflozin 100 mg | Canagliflozin 300 mg | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/89 (0%) | 1/98 (1%) | 0/93 (0%) | 0/96 (0%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Arthralgia | 0/89 (0%) | 1/98 (1%) | 0/93 (0%) | 0/96 (0%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| Placebo | Canagliflozin 50 mg | Canagliflozin 100 mg | Canagliflozin 300 mg | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 28/89 (31.5%) | 41/98 (41.8%) | 30/93 (32.3%) | 31/96 (32.3%) | ||||
| Gastrointestinal disorders | ||||||||
| Constipation | 2/89 (2.2%) | 5/98 (5.1%) | 3/93 (3.2%) | 2/96 (2.1%) | ||||
| Diarrhoea | 5/89 (5.6%) | 5/98 (5.1%) | 3/93 (3.2%) | 2/96 (2.1%) | ||||
| Nausea | 2/89 (2.2%) | 7/98 (7.1%) | 6/93 (6.5%) | 3/96 (3.1%) | ||||
| Infections and infestations | ||||||||
| Nasopharyngitis | 3/89 (3.4%) | 6/98 (6.1%) | 1/93 (1.1%) | 1/96 (1%) | ||||
| Sinusitis | 0/89 (0%) | 6/98 (6.1%) | 2/93 (2.2%) | 1/96 (1%) | ||||
| Upper respiratory tract infection | 5/89 (5.6%) | 6/98 (6.1%) | 6/93 (6.5%) | 5/96 (5.2%) | ||||
| Urinary tract infection | 6/89 (6.7%) | 10/98 (10.2%) | 7/93 (7.5%) | 8/96 (8.3%) | ||||
| Vulvovaginal mycotic infection | 1/89 (1.1%) | 8/98 (8.2%) | 5/93 (5.4%) | 14/96 (14.6%) | ||||
| Nervous system disorders | ||||||||
| Headache | 7/89 (7.9%) | 6/98 (6.1%) | 11/93 (11.8%) | 4/96 (4.2%) | ||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
A copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested in writing, such publication will be withheld for up to an additional 60 days.
Results Point of Contact
| Name/Title | Vice President, Franchise Medical Leader, Cardiovascular & Metabolism Franchise |
|---|---|
| Organization | Janssen Research & Development, LLC |
| Phone | 1 800 526 7736 |
Responsible Party:
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier:
NCT00650806
Other Study ID Numbers:
- CR014578
- 28431754OBE2001
First Posted:
Apr 2, 2008
Last Update Posted:
May 24, 2013
Last Verified:
Apr 1, 2013