Obesity
Conditions
Brief summary
The objective of this study is to evaluate the safety and efficacy of various doses of VI-0521 compared to both placebo, and the single-agent components that comprise each combination dose. This study will provide confirmatory data to demonstrate that doses of VI-0521 have efficacy that is greater than placebo and each of the single-agent components that comprise the combination dose.
Interventions
DRUGVI-0521
phentermine 15 mg and topiramate 92 mg, po once daily
DRUGtopiramate
topiramate 46 mg, po once daily
DRUGphentermine
phentermine 7.5 mg, po once daily
Sponsors
Medpace, Inc.
VIVUS LLC
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 70 Years
Healthy volunteers
No
Inclusion criteria
* 70 years of age or less with body mass index (BMI) between 30 and 45 kg/m2 * Informed Consent * Females of child-bearing potential must be using adequate contraception
Exclusion criteria
* Stroke/myocardial infarction (MI)/unstable cardiovascular disease within 6 months * Clinically significant renal, hepatic or psychiatric disease * Unstable thyroid disease or replacement therapy * Nephrolithiasis * Obesity of known genetic or endocrine origin * Participation in a formal weight loss program or lifestyle intervention * Glaucoma or elevated intraocular pressure * Pregnancy or breastfeeding * Drug or Alcohol abuse * Smoking cessation within previous 3 months or plans to quit smoking during study * Eating disorders within past year * Cholelithiasis within past 6 months * Type 2 diabetes * Previous bariatric surgery * Bipolar disorder or psychosis * Steroid hormone therapy not stable for 3 months * Systolic blood pressure \> 160 mmHg, diastolic blood pressure \> 100 mmHg
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With at Least 5% Weight Loss at Week 28 With LOCF | baseline to 28 weeks | — |
| Percent Weight Loss From Baseline to Week 28 | baseline to 28 weeks | Percent weight loss from baseline to Week 28 with last observation carried forward (LOCF) |
Countries
United States
Participant flow
Recruitment details
Subject recruitment occurred at investigative sites in the US between November 2007 through January 2008
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo | 109 |
| PHEN 7.5 mg 7.5 mg phentermine | 109 |
| TPM 46 mg 46 mg topiramate | 108 |
| VI-0521 Mid 7.5 mg/46 mg phentermine/topiramate | 107 |
| PHEN 15 mg 15 mg phentermine | 108 |
| TPM 92 mg 92 mg topiramate | 107 |
| VI-0521 Top 15 mg/92 mg phentermine/topiramate | 108 |
| Total | 756 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 4 | 5 | 9 | 6 | 10 | 17 |
| Overall Study | Lost to Follow-up | 14 | 14 | 12 | 6 | 9 | 8 | 9 |
| Overall Study | Other | 5 | 5 | 3 | 4 | 4 | 4 | 0 |
| Overall Study | Pregnancy | 1 | 0 | 1 | 2 | 1 | 2 | 0 |
| Overall Study | protocol non-compliance | 1 | 1 | 2 | 1 | 0 | 1 | 3 |
| Overall Study | requirement for restricted medication | 0 | 0 | 2 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 11 | 6 | 5 | 7 | 8 | 5 | 4 |
Baseline characteristics
| Characteristic | Placebo | PHEN 7.5 mg | TPM 46 mg | VI-0521 Mid | PHEN 15 mg | TPM 92 mg | VI-0521 Top | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 45 years STANDARD_DEVIATION 11.43 | 46.4 years STANDARD_DEVIATION 11.57 | 46.9 years STANDARD_DEVIATION 12.62 | 44.6 years STANDARD_DEVIATION 11.07 | 45.7 years STANDARD_DEVIATION 12.38 | 45.8 years STANDARD_DEVIATION 11.21 | 44.6 years STANDARD_DEVIATION 12.84 | 45.6 years STANDARD_DEVIATION 11.88 |
| Region of Enrollment United States | 109 participants | 109 participants | 108 participants | 107 participants | 108 participants | 107 participants | 108 participants | 756 participants |
| Sex: Female, Male Female | 86 Participants | 86 Participants | 86 Participants | 85 Participants | 86 Participants | 85 Participants | 85 Participants | 599 Participants |
| Sex: Female, Male Male | 23 Participants | 23 Participants | 22 Participants | 22 Participants | 22 Participants | 22 Participants | 23 Participants | 157 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 87 / 109 | 85 / 109 | 90 / 106 | 84 / 106 | 88 / 108 | 84 / 107 | 88 / 108 |
| serious Total, serious adverse events | 0 / 109 | 2 / 109 | 0 / 106 | 1 / 106 | 1 / 108 | 1 / 107 | 2 / 108 |
Outcome results
Primary
Percentage of Subjects With at Least 5% Weight Loss at Week 28 With LOCF
Time frame: baseline to 28 weeks
Population: Intent-to-treat Last-observation-carried-forward (ITT-LOCF)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Subjects With at Least 5% Weight Loss at Week 28 With LOCF | 15.5 percentage of participants |
| PHEN 7.5 mg | Percentage of Subjects With at Least 5% Weight Loss at Week 28 With LOCF | 43.3 percentage of participants |
| TPM 46 mg | Percentage of Subjects With at Least 5% Weight Loss at Week 28 With LOCF | 39.2 percentage of participants |
| VI-0521 Mid | Percentage of Subjects With at Least 5% Weight Loss at Week 28 With LOCF | 62.1 percentage of participants |
| PHEN 15 mg | Percentage of Subjects With at Least 5% Weight Loss at Week 28 With LOCF | 46.2 percentage of participants |
| TPM 92 mg | Percentage of Subjects With at Least 5% Weight Loss at Week 28 With LOCF | 48.6 percentage of participants |
| VI-0521 Top | Percentage of Subjects With at Least 5% Weight Loss at Week 28 With LOCF | 66.0 percentage of participants |
Comparison: With 100 subjects in each of the seven arms in this trial, the trial has more than 90% power to detect a difference of at least 3.1% between combination and monotherapy or placebo treatment assuming a standard deviation of 5.3% and a significance level of 0.05.p-value: 0.01495% CI: [1.154, 3.563]Regression, Logistic
Comparison: With 100 subjects in each of the seven arms in this trial, the trial has more than 90% power to detect a difference of at least 3.1% between combination and monotherapy or placebo treatment assuming a standard deviation of 5.3% and a significance level of 0.05.p-value: 0.004695% CI: [1.283, 3.932]Regression, Logistic
Comparison: With 100 subjects in each of the seven arms in this trial, the trial has more than 90% power to detect a difference of at least 3.1% between combination and monotherapy or placebo treatment assuming a standard deviation of 5.3% and a significance level of 0.05.p-value: <0.000195% CI: [5.424, 20.81]Regression, Logistic
Comparison: With 100 subjects in each of the seven arms in this trial, the trial has more than 90% power to detect a difference of at least 3.1% between combination and monotherapy or placebo treatment assuming a standard deviation of 5.3% and a significance level of 0.05.p-value: 0.001195% CI: [1.46, 4.514]Regression, Logistic
Comparison: With 100 subjects in each of the seven arms in this trial, the trial has more than 90% power to detect a difference of at least 3.1% between combination and monotherapy or placebo treatment assuming a standard deviation of 5.3% and a significance level of 0.05.p-value: 0.006695% CI: [1.241, 3.781]Regression, Logistic
Comparison: With 100 subjects in each of the seven arms in this trial, the trial has more than 90% power to detect a difference of at least 3.1% between combination and monotherapy or placebo treatment assuming a standard deviation of 5.3% and a significance level of 0.05.p-value: <0.000195% CI: [4.65, 17.66]Regression, Logistic
Primary
Percent Weight Loss From Baseline to Week 28
Percent weight loss from baseline to Week 28 with last observation carried forward (LOCF)
Time frame: baseline to 28 weeks
Population: Intent-to-treat Last-observation-carried-forward (ITT-LOCF)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Weight Loss From Baseline to Week 28 | 1.7 percent weight loss | Standard Error 0.61 |
| PHEN 7.5 mg | Percent Weight Loss From Baseline to Week 28 | 5.5 percent weight loss | Standard Error 0.61 |
| TPM 46 mg | Percent Weight Loss From Baseline to Week 28 | 5.1 percent weight loss | Standard Error 0.61 |
| VI-0521 Mid | Percent Weight Loss From Baseline to Week 28 | 8.5 percent weight loss | Standard Error 0.62 |
| PHEN 15 mg | Percent Weight Loss From Baseline to Week 28 | 6.1 percent weight loss | Standard Error 0.61 |
| TPM 92 mg | Percent Weight Loss From Baseline to Week 28 | 6.4 percent weight loss | Standard Error 0.62 |
| VI-0521 Top | Percent Weight Loss From Baseline to Week 28 | 9.2 percent weight loss | Standard Error 0.61 |
Comparison: With 100 subjects in each of the seven arms in this trial, the trial has more than 90% power to detect a difference of at least 3.1% between combination and monotherapy or placebo treatment assuming a standard deviation of 5.3% and a significance level of 0.05.p-value: 0.000995% CI: [1.13, 4.39]ANCOVA
Comparison: With 100 subjects in each of the seven arms in this trial, the trial has more than 90% power to detect a difference of at least 3.1% between combination and monotherapy or placebo treatment assuming a standard deviation of 5.3% and a significance level of 0.05.p-value: 0.000195% CI: [1.53, 4.77]ANCOVA
Comparison: With 100 subjects in each of the seven arms in this trial, the trial has more than 90% power to detect a difference of at least 3.1% between combination and monotherapy or placebo treatment assuming a standard deviation of 5.3% and a significance level of 0.05.p-value: <0.000195% CI: [5.86, 9.12]ANCOVA
Comparison: With 100 subjects in each of the seven arms in this trial, the trial has more than 90% power to detect a difference of at least 3.1% between combination and monotherapy or placebo treatment assuming a standard deviation of 5.3% and a significance level of 0.05.p-value: <0.000195% CI: [1.69, 4.96]ANCOVA
Comparison: With 100 subjects in each of the seven arms in this trial, the trial has more than 90% power to detect a difference of at least 3.1% between combination and monotherapy or placebo treatment assuming a standard deviation of 5.3% and a significance level of 0.05.p-value: 0.000395% CI: [1.38, 4.63]ANCOVA
Comparison: With 100 subjects in each of the seven arms in this trial, the trial has more than 90% power to detect a difference of at least 3.1% between combination and monotherapy or placebo treatment assuming a standard deviation of 5.3% and a significance level of 0.05.p-value: <0.000195% CI: [5.11, 8.38]ANCOVA