Obesity
Conditions
Keywords
Obesity, Overweight, Canagliflozin, Phentermine, INVOKANA®
Brief summary
The purpose of this study is to compare the effects of canagliflozin and phentermine to those of placebo to promote on a change in body weight over a 26 week period.
Detailed description
This is a randomized (the study medication is assigned by chance), double-blind (neither physician nor participant knows the identity of the assigned treatment), placebo-controlled (an inactive substance that is compared with a medication to test whether the medication has a real effect), parallel-group, multicenter study of the effects of canagliflozin and phentermine co-administration in non-diabetic overweight or obese participants. The study will be conducted for about 33 weeks, approximately 344 participants will be randomly assigned in a 1:1:1:1 ratio to one of the four treatment groups: co-administration of canagliflozin and phentermine, canagliflozin alone, phentermine alone, or placebo. All participants will be also provided with diet and exercise counseling for weight loss (standardized non-pharmacological therapy).
Interventions
DRUGCanagliflozin
300 mg capsule, taken once daily, orally for 26 weeks.
DRUGPhentermine
15 mg capsule, taken once daily, orally for 26 weeks.
DRUGMatching Placebo to Canagliflozin
Placebo capsules look like canagliflozin but do not contain any active drug, taken once daily, orally for 26 weeks.
DRUGMatching Placebo to Phentermine
Placebo capsules look like phentermine but do not contain any active drug, taken once daily, orally for 26 weeks.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Must have BMI \>=30 kg/m2 and \<50 kg/m2 at screening or BMI \>=27 kg/m2 and \<50 kg/m2 at screening in the presence of a comorbidity of hypertension and/or dyslipidemia * Must have stable weight, ie, change of \< =5% in the 3 months before screening * Must agree to utilize a highly effective method of birth control
Exclusion criteria
* An established diagnosis of diabetes mellitus * Has a history of obesity with a known secondary cause (eg, Cushing's disease/syndrome) * Has a history of hereditary glucose-galactose malabsorption or primary renal glycosuria * Myocardial infarction, unstable angina, revascularization procedure, or cerebrovascular accident within 12 weeks before screening * Has an Glycated hemoglobin (HBA1c) greater than or equal (\>=) to 65 percent * An average of 3 seated blood pressure (BP) readings of systolic BP \>= 160 mm Hg and/or Diastolic BP \>= 100 millimeters of mercury at screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Body Weight at Week 26 | Week 26 | The percent change from baseline in body weight at Week 26 was analysed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Weight Loss More Than Equal to (>=) 5 Percent at Week 26 | Week 26 | Percentage of participants with weight loss \>= 5 percent were analysed at week 26. |
| Change From Baseline in Systolic Blood Pressure at Week 26 | Week 26 | Change from baseline in systolic blood pressure was analysed at week 26. |
| Absolute Change From Baseline in Body Weight at Week 26 | Week 26 | Absolute change from baseline in body weight was analysed at week 26. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Pulse Rate at Week 26 | Week 26 | Change from baseline in pulse rate at week 26 |
| Percentage of Participants With Weight Loss More Than Equal to (>=) 10 Percent at Week 26 | Week 26 | Percentage of participants with weight loss \>= 10 percent at week 26. |
| Change From Baseline in Diastolic Blood Pressure (DBP) at Week 26 | Week 26 | Change from baseline in diastolic blood pressure (DBP) at week 26. |
Countries
United States
Participant flow
Pre-assignment details
Between screening and randomisation, eligible subjects were included in a 4-week single-blind run-in period in which all subjects were placed on a hypocaloric diet.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo tablets orally for 26 weeks. | 82 |
| Phentermine 15 mg Participants received phentermine 15 mg over-encapsulated tablets orally for 26 weeks. | 85 |
| Canagliflozin 300 mg Participants received canagliflozin 300 mg over-encapsulated tablets orally for 26 weeks. | 84 |
| Canagliflozin 300 mg/Phentermine 15 mg Participants received co-administration of canagliflozin 300 mg and phentermine 15 mg orally for 26 weeks. | 83 |
| Total | 334 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 5 | 6 | 10 | 4 |
| Overall Study | Lost to Follow-up | 9 | 9 | 14 | 11 |
| Overall Study | Other | 1 | 3 | 1 | 2 |
| Overall Study | Protocol Violation | 3 | 1 | 2 | 1 |
| Overall Study | Randomized but not received treatment | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 7 | 6 | 4 | 4 |
Baseline characteristics
| Characteristic | Total | Canagliflozin 300 mg/Phentermine 15 mg | Placebo | Canagliflozin 300 mg | Phentermine 15 mg |
|---|---|---|---|---|---|
| Age, Continuous | 45.7 years STANDARD_DEVIATION 11.41 | 46.3 years STANDARD_DEVIATION 12.45 | 44.8 years STANDARD_DEVIATION 11.09 | 45.2 years STANDARD_DEVIATION 11.02 | 46.4 years STANDARD_DEVIATION 11.14 |
| Baseline Body Mass Index (BMI) | 37.3 kilogram per meter square [kg/m²] STANDARD_DEVIATION 5.16 | 36.8 kilogram per meter square [kg/m²] STANDARD_DEVIATION 5.36 | 38 kilogram per meter square [kg/m²] STANDARD_DEVIATION 5.2 | 37.3 kilogram per meter square [kg/m²] STANDARD_DEVIATION 4.68 | 37 kilogram per meter square [kg/m²] STANDARD_DEVIATION 5.4 |
| Baseline Diastolic Blood Pressure | 79.1 millimeters of mercury [mmHg] STANDARD_DEVIATION 8.39 | 79.4 millimeters of mercury [mmHg] STANDARD_DEVIATION 8.21 | 78.8 millimeters of mercury [mmHg] STANDARD_DEVIATION 8.43 | 80.2 millimeters of mercury [mmHg] STANDARD_DEVIATION 7.88 | 78.1 millimeters of mercury [mmHg] STANDARD_DEVIATION 9 |
| Baseline Pulse Rate | 72.0 (BEATS/MIN) STANDARD_DEVIATION 9.5 | 72.4 (BEATS/MIN) STANDARD_DEVIATION 9.66 | 73.5 (BEATS/MIN) STANDARD_DEVIATION 8.72 | 71.5 (BEATS/MIN) STANDARD_DEVIATION 9.4 | 70.7 (BEATS/MIN) STANDARD_DEVIATION 10.09 |
| Baseline Systolic Blood Pressure | 123.7 millimeters of mercury [mmHg] STANDARD_DEVIATION 12.87 | 124.8 millimeters of mercury [mmHg] STANDARD_DEVIATION 12.83 | 122.5 millimeters of mercury [mmHg] STANDARD_DEVIATION 13.86 | 124.5 millimeters of mercury [mmHg] STANDARD_DEVIATION 13.01 | 123.0 millimeters of mercury [mmHg] STANDARD_DEVIATION 11.83 |
| Baseline Weight | 102.9 Kilogram [kg] STANDARD_DEVIATION 18.28 | 101.1 Kilogram [kg] STANDARD_DEVIATION 18.07 | 104.3 Kilogram [kg] STANDARD_DEVIATION 18.16 | 103.3 Kilogram [kg] STANDARD_DEVIATION 19.14 | 102.8 Kilogram [kg] STANDARD_DEVIATION 17.89 |
| Region of Enrollment United States | 334 participants | 83 participants | 82 participants | 84 participants | 85 participants |
| Sex: Female, Male Female | 273 Participants | 69 Participants | 67 Participants | 68 Participants | 69 Participants |
| Sex: Female, Male Male | 61 Participants | 14 Participants | 15 Participants | 16 Participants | 16 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 | 41 / 82 | 37 / 85 | 42 / 84 | 42 / 83 |
| serious Total, serious adverse events | 0 / 82 | 0 / 85 | 0 / 84 | 1 / 83 |
Outcome results
Primary
Percent Change From Baseline in Body Weight at Week 26
The percent change from baseline in body weight at Week 26 was analysed.
Time frame: Week 26
Population: The modified intent-to-treat (mITT) analysis set included all randomized participants who received at least 1 dose of double-blind study agent. N=number of participants analysed is the total participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Body Weight at Week 26 | -0.6 Percent Change | Standard Error 0.6 |
| Phentermine 15 mg | Percent Change From Baseline in Body Weight at Week 26 | -4.1 Percent Change | Standard Error 0.6 |
| Canagliflozin 300 mg | Percent Change From Baseline in Body Weight at Week 26 | -1.9 Percent Change | Standard Error 0.6 |
| Canagliflozin 300 mg/Phentermine 15 mg | Percent Change From Baseline in Body Weight at Week 26 | -7.5 Percent Change | Standard Error 0.6 |
p-value: <0.00195% CI: [-5.3, -1.8]Mixed Model for Repeated Measures
p-value: 0.14295% CI: [-3.1, 0.4]Mixed Model for Repeated Measures
p-value: <0.00195% CI: [-8.6, -5.2]Mixed Model for Repeated Measures
Secondary
Absolute Change From Baseline in Body Weight at Week 26
Absolute change from baseline in body weight was analysed at week 26.
Time frame: Week 26
Population: The mITT analysis set included all randomized participants who received at least 1 dose of double-blind study agent. N=number of participants analysed is the total participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Absolute Change From Baseline in Body Weight at Week 26 | -0.6 Kilogram (Kg) | Standard Error 0.6 |
| Phentermine 15 mg | Absolute Change From Baseline in Body Weight at Week 26 | -4.1 Kilogram (Kg) | Standard Error 0.6 |
| Canagliflozin 300 mg | Absolute Change From Baseline in Body Weight at Week 26 | -1.9 Kilogram (Kg) | Standard Error 0.7 |
| Canagliflozin 300 mg/Phentermine 15 mg | Absolute Change From Baseline in Body Weight at Week 26 | -7.3 Kilogram (Kg) | Standard Error 0.6 |
p-value: <0.00195% CI: [-5.3, -1.7]Mixed Model for Repeated Measures
p-value: 0.15395% CI: [-3.1, 0.5]Mixed Model for Repeated Measures
p-value: <0.00195% CI: [-8.5, -4.9]Mixed Model for Repeated Measures
Secondary
Change From Baseline in Systolic Blood Pressure at Week 26
Change from baseline in systolic blood pressure was analysed at week 26.
Time frame: Week 26
Population: The mITT analysis set included all randomized participants who received at least 1 dose of double-blind study agent. N=number of participants analysed is the total participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Systolic Blood Pressure at Week 26 | -2.7 mmHg (millimeters of mercury) | Standard Error 1.3 |
| Phentermine 15 mg | Change From Baseline in Systolic Blood Pressure at Week 26 | -1.4 mmHg (millimeters of mercury) | Standard Error 1.2 |
| Canagliflozin 300 mg | Change From Baseline in Systolic Blood Pressure at Week 26 | -3.1 mmHg (millimeters of mercury) | Standard Error 1.3 |
| Canagliflozin 300 mg/Phentermine 15 mg | Change From Baseline in Systolic Blood Pressure at Week 26 | -6.9 mmHg (millimeters of mercury) | Standard Error 1.2 |
p-value: 0.45695% CI: [-2.1, 4.8]Mixed Model for Repeated Measures
p-value: 0.82795% CI: [-3.9, 3.1]Mixed Model for Repeated Measures
p-value: 0.01595% CI: [-7.7, -0.8]Mixed Model for Repeated Measures
Secondary
Percentage of Participants With Weight Loss More Than Equal to (>=) 5 Percent at Week 26
Percentage of participants with weight loss \>= 5 percent were analysed at week 26.
Time frame: Week 26
Population: The mITT analysis set included all randomized participants who received at least 1 dose of double-blind study agent. N=number of participants analysed is the total participants who were evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Weight Loss More Than Equal to (>=) 5 Percent at Week 26 | 17.5 percentage of participants |
| Phentermine 15 mg | Percentage of Participants With Weight Loss More Than Equal to (>=) 5 Percent at Week 26 | 41.7 percentage of participants |
| Canagliflozin 300 mg | Percentage of Participants With Weight Loss More Than Equal to (>=) 5 Percent at Week 26 | 17.9 percentage of participants |
| Canagliflozin 300 mg/Phentermine 15 mg | Percentage of Participants With Weight Loss More Than Equal to (>=) 5 Percent at Week 26 | 66.7 percentage of participants |
p-value: 0.00295% CI: [1.7, 10.14]Generalized linear Mixed Model
p-value: 0.82595% CI: [0.41, 3.06]Generalized linear Mixed Model
p-value: <0.00195% CI: [4.15, 25.05]Generalized linear Mixed Model
Other Pre-specified
Change From Baseline in Diastolic Blood Pressure (DBP) at Week 26
Change from baseline in diastolic blood pressure (DBP) at week 26.
Time frame: Week 26
Population: The mITT analysis set included all randomized participants who received at least 1 dose of double-blind study agent. N=number of participants analysed is the total participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Diastolic Blood Pressure (DBP) at Week 26 | -0.9 mmHg (millimeters of mercury) | Standard Error 0.9 |
| Phentermine 15 mg | Change From Baseline in Diastolic Blood Pressure (DBP) at Week 26 | 0.1 mmHg (millimeters of mercury) | Standard Error 0.8 |
| Canagliflozin 300 mg | Change From Baseline in Diastolic Blood Pressure (DBP) at Week 26 | -1.5 mmHg (millimeters of mercury) | Standard Error 0.9 |
| Canagliflozin 300 mg/Phentermine 15 mg | Change From Baseline in Diastolic Blood Pressure (DBP) at Week 26 | -2.5 mmHg (millimeters of mercury) | Standard Error 0.8 |
Other Pre-specified
Change From Baseline in Pulse Rate at Week 26
Change from baseline in pulse rate at week 26
Time frame: Week 26
Population: The modified intent-to-treat (mITT) analysis set included all randomized participants who received at least 1 dose of double-blind study agent. N=number of participants analysed is the total participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Pulse Rate at Week 26 | -0.7 Beats Per Minute (Beats/Min) | Standard Error 1 |
| Phentermine 15 mg | Change From Baseline in Pulse Rate at Week 26 | 4.1 Beats Per Minute (Beats/Min) | Standard Error 1 |
| Canagliflozin 300 mg | Change From Baseline in Pulse Rate at Week 26 | 0.7 Beats Per Minute (Beats/Min) | Standard Error 1 |
| Canagliflozin 300 mg/Phentermine 15 mg | Change From Baseline in Pulse Rate at Week 26 | 3.5 Beats Per Minute (Beats/Min) | Standard Error 0.9 |
Other Pre-specified
Percentage of Participants With Weight Loss More Than Equal to (>=) 10 Percent at Week 26
Percentage of participants with weight loss \>= 10 percent at week 26.
Time frame: Week 26
Population: The mITT analysis set included all randomized participants who received at least 1 dose of double-blind study agent.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Weight Loss More Than Equal to (>=) 10 Percent at Week 26 | 8.8 Percentage of Participants |
| Phentermine 15 mg | Percentage of Participants With Weight Loss More Than Equal to (>=) 10 Percent at Week 26 | 8.3 Percentage of Participants |
| Canagliflozin 300 mg | Percentage of Participants With Weight Loss More Than Equal to (>=) 10 Percent at Week 26 | 5.4 Percentage of Participants |
| Canagliflozin 300 mg/Phentermine 15 mg | Percentage of Participants With Weight Loss More Than Equal to (>=) 10 Percent at Week 26 | 34.9 Percentage of Participants |