Blood Pressure
Conditions
Keywords
Obesity, Overweight, Qsymia, ABPM
Brief summary
The study is being conducted to evaluate the effect of VI-0521 (Qsymia®) on blood pressure as measured by 24-hour ambulatory blood pressure monitoring, compared to both placebo and an active control (phentermine 30 mg).
Interventions
DRUGVI-0521
Phentermine/Topiramate Top Dose 15 mg/92 mg capsule
DRUGPhentermine
Phentermine 30 mg capsule
DRUGPlacebo
Inactive oral capsule
Sponsors
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 75 Years
Healthy volunteers
No
Inclusion criteria
* Overweight/obese adult males/females 18-75 years of age with a BMI ≥ 27 kg/m2; * At least 1 weight-related comorbidity (i.e., hypertension, dyslipidemia, Type 2 diabetes mellitus \[T2DM\] or prediabetes, or obstructive sleep apnea). * Must be ambulatory, willing, and able to wear ABPM monitor apparatus for 24 hours at beginning and end of study.
Exclusion criteria
* Screening blood pressure of \> 140/90 mmHg; * Type 1 diabetes; T2DM treated with SFUs, GLP-1 receptor agonists, SGLT inhibitors; or not on stable diabetic medications for at least 3 months prior to randomization; * Clinically significant cardiac, hepatic, renal, pulmonary, or thyroid disease; * History of bipolar disorder, psychosis, greater than one lifetime episode of major depressive disorder, or presence or history of suicidal behavior or suicidal ideation with intent to act; * History of glaucoma; * Night shift workers; * Obesity of known genetic or endocrine origin; recent history of weight instability, or recent participation in a formal weight loss program within 3 months prior to screening; and * Smoking cessation within 3 months prior to screening; * Use of antihypertensive medications, antidiabetic medications, statins or other lipid lowering agents, or CPAP therapy that has not been stable for at least 3 months prior to randomization; * COVID-19 vaccination or treatment for severe COVID-19 infection within a month prior to randomization.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 8 in Mean Systolic Blood Pressure as Measured by 24-hr ABPM | Baseline to Week 8 | The change between systolic blood pressure measured at Week 8 relative to the baseline measurements from the ABPM data read out. Blood pressure and heart rate were measured every 20 minutes from 6:00 to 22:00 hours, and every 30 minutes from 22:01 to 5:59 hours for 24 consecutive hours, while subjects continue normal routine activities. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 8 in Mean Diastolic Blood Pressure as Measured by 24-hr ABPM | Baseline to Week 8 | The change between diastolic blood pressure measured at Week 8 relative to the baseline measurements from the ABPM data read out. Blood pressure and heart rate were measured every 20 minutes from 6:00 to 22:00 hours, and every 30 minutes from 22:01 to 5:59 hours for 24 consecutive hours, while subjects continue normal routine activities. |
| Mean Change in Systolic and Diastolic Blood Pressure From Baseline to Week 8 as Measured in Clinic | Baseline to Week 8 | The change between systolic and diastolic blood pressure measured in the clinic at Week 8 relative to the baseline measurements after subjects are seated comfortably for at least 10 minutes prior to taking blood pressure. In clinic blood pressure for determining hypertension was the average of three successive blood pressure readings, collected at least 2 minutes apart. The mean of the three values was be recorded as the subject's blood pressure. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| VI-0521 Top Dose (Phentermine 15 mg + Topiramate 92 mg) Week 1: VI-0521 (Phentermine 3.75 mg + Topiramate 23 mg) oral capsule, once daily; Week 2: VI-0521 (Phentermine 7.5 mg + Topiramate 46 mg) oral capsule, once daily; Week 3: VI-0521 (Phentermine 11.25 mg + Topiramate 69 mg) oral capsule, once daily; Weeks 4-8: VI-0521 (Phentermine 15 mg + Topiramate 92 mg) oral capsule, once daily
VI-0521: Phentermine/Topiramate Top Dose 15 mg/92 mg capsule | 190 |
| Phentermine 30mg Weeks 1-8: Phentermine 30mg oral capsule, once daily
Phentermine: Phentermine 30 mg capsule | 191 |
| Placebo Weeks 1-8: Placebo oral capsule, once daily
Placebo: Inactive oral capsule | 184 |
| Total | 565 |
Baseline characteristics
| Characteristic | Phentermine 30mg | Total | Placebo | VI-0521 Top Dose (Phentermine 15 mg + Topiramate 92 mg) |
|---|---|---|---|---|
| Age, Continuous | 53.3 years STANDARD_DEVIATION 12.12 | 53.4 years STANDARD_DEVIATION 12.29 | 53.3 years STANDARD_DEVIATION 11.36 | 53.6 years STANDARD_DEVIATION 13.34 |
| Blood Pressure Diastolic Blood Pressure | 77.0 mmHg STANDARD_DEVIATION 7.98 | 77.6 mmHg STANDARD_DEVIATION 7.78 | 78.3 mmHg STANDARD_DEVIATION 7.71 | 77.5 mmHg STANDARD_DEVIATION 7.63 |
| Blood Pressure Systolic Blood Pressure | 123.4 mmHg STANDARD_DEVIATION 10.38 | 123.9 mmHg STANDARD_DEVIATION 10.48 | 124.5 mmHg STANDARD_DEVIATION 11.23 | 123.9 mmHg STANDARD_DEVIATION 9.82 |
| BMI (Body Mass Index) | 35.4 kg/m2 STANDARD_DEVIATION 5.88 | 35.8 kg/m2 STANDARD_DEVIATION 6.08 | 36.2 kg/m2 STANDARD_DEVIATION 6.17 | 35.7 kg/m2 STANDARD_DEVIATION 6.2 |
| Diabetes Status Borderline Diabetes | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Diabetes Status Gestational Diabetes | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Diabetes Status Not Diabetic | 148 Participants | 423 Participants | 138 Participants | 137 Participants |
| Diabetes Status Prediabetes | 24 Participants | 76 Participants | 25 Participants | 27 Participants |
| Diabetes Status Type 2 Diabetes | 19 Participants | 64 Participants | 20 Participants | 25 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 50 Participants | 149 Participants | 47 Participants | 52 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 141 Participants | 416 Participants | 137 Participants | 138 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Height | 166.6 cm STANDARD_DEVIATION 9.51 | 166.2 cm STANDARD_DEVIATION 9.58 | 166.1 cm STANDARD_DEVIATION 10.08 | 165.7 cm STANDARD_DEVIATION 9.16 |
| Hypertensive status Medical Diagnosis of Hypertension Treated with 0 to 2 Antihypertensive Agents | 120 Participants | 353 Participants | 117 Participants | 116 Participants |
| Hypertensive status Medical Diagnosis of Hypertension Treated with 3 or More Antihypertensive Agents | 10 Participants | 29 Participants | 9 Participants | 10 Participants |
| Hypertensive status No Medical Diagnosis of or Treatment for Hypertension | 61 Participants | 183 Participants | 58 Participants | 64 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 5 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 5 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 17 Participants | 81 Participants | 39 Participants | 25 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 4 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 3 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 6 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) White | 167 Participants | 461 Participants | 140 Participants | 154 Participants |
| Region of Enrollment United States | 191 participants | 565 participants | 184 participants | 190 participants |
| Sex: Female, Male Female | 142 Participants | 415 Participants | 137 Participants | 136 Participants |
| Sex: Female, Male Male | 49 Participants | 150 Participants | 47 Participants | 54 Participants |
| Weight | 99.5 kg STANDARD_DEVIATION 21.58 | 99.6 kg STANDARD_DEVIATION 21.29 | 100.4 kg STANDARD_DEVIATION 21.52 | 98.8 kg STANDARD_DEVIATION 20.84 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 190 | 0 / 191 | 0 / 184 |
| other Total, other adverse events | 66 / 190 | 44 / 191 | 6 / 184 |
| serious Total, serious adverse events | 0 / 190 | 1 / 191 | 0 / 184 |
Outcome results
Primary
Change From Baseline to Week 8 in Mean Systolic Blood Pressure as Measured by 24-hr ABPM
The change between systolic blood pressure measured at Week 8 relative to the baseline measurements from the ABPM data read out. Blood pressure and heart rate were measured every 20 minutes from 6:00 to 22:00 hours, and every 30 minutes from 22:01 to 5:59 hours for 24 consecutive hours, while subjects continue normal routine activities.
Time frame: Baseline to Week 8
Population: Subjects who completed the study per protocol. Per Protocol Population (PPP) was defined as:~1. Randomized and received at least one dose of study drug;~2. ≥ 80% treatment compliance;~3. Last daily dose of study drug administered on the same date that ABPM was initiated at Week 8/End of Study or early termination (EOS);~4. ≥ 23.5 hours of ABPM data at baseline and at Week 8/EOS or early termination, and ≥ 75% ABPM readings;~5. No major protocol deviation that impacted ABPM readings.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| VI-0521 Top Dose (Phentermine 15 mg + Topiramate 92 mg) | Change From Baseline to Week 8 in Mean Systolic Blood Pressure as Measured by 24-hr ABPM | -3.3 mmHg | Standard Error 1.07 |
| Phentermine 30mg | Change From Baseline to Week 8 in Mean Systolic Blood Pressure as Measured by 24-hr ABPM | 1.4 mmHg | Standard Error 1.05 |
| Placebo | Change From Baseline to Week 8 in Mean Systolic Blood Pressure as Measured by 24-hr ABPM | -0.1 mmHg | Standard Error 1.04 |
p-value: <0.001ANCOVA
p-value: 0.0059ANCOVA
p-value: 0.1867ANCOVA
Secondary
Change From Baseline to Week 8 in Mean Diastolic Blood Pressure as Measured by 24-hr ABPM
The change between diastolic blood pressure measured at Week 8 relative to the baseline measurements from the ABPM data read out. Blood pressure and heart rate were measured every 20 minutes from 6:00 to 22:00 hours, and every 30 minutes from 22:01 to 5:59 hours for 24 consecutive hours, while subjects continue normal routine activities.
Time frame: Baseline to Week 8
Population: Subjects who completed the study per protocol. Per Protocol Population (PPP) was defined as:~1. Randomized and received at least one dose of study drug;~2. ≥ 80% treatment compliance;~3. Last daily dose of study drug administered on the same date that ABPM was initiated at Week 8/End of Study or early termination (EOS);~4. ≥ 23.5 hours of ABPM data at baseline and at Week 8/EOS or early termination, and ≥ 75% ABPM readings;~5. No major protocol deviation that impacted ABPM readings.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| VI-0521 Top Dose (Phentermine 15 mg + Topiramate 92 mg) | Change From Baseline to Week 8 in Mean Diastolic Blood Pressure as Measured by 24-hr ABPM | 0.8 mmHg | Standard Error 0.64 |
| Phentermine 30mg | Change From Baseline to Week 8 in Mean Diastolic Blood Pressure as Measured by 24-hr ABPM | 2.4 mmHg | Standard Error 0.64 |
| Placebo | Change From Baseline to Week 8 in Mean Diastolic Blood Pressure as Measured by 24-hr ABPM | -0.4 mmHg | Standard Error 0.63 |
p-value: 0.0277ANCOVA
p-value: 0.0852ANCOVA
p-value: <0.0001ANCOVA
Secondary
Mean Change in Systolic and Diastolic Blood Pressure From Baseline to Week 8 as Measured in Clinic
The change between systolic and diastolic blood pressure measured in the clinic at Week 8 relative to the baseline measurements after subjects are seated comfortably for at least 10 minutes prior to taking blood pressure. In clinic blood pressure for determining hypertension was the average of three successive blood pressure readings, collected at least 2 minutes apart. The mean of the three values was be recorded as the subject's blood pressure.
Time frame: Baseline to Week 8
Population: Subjects who completed the study per protocol. Per Protocol Population (PPP) was defined as:~1. Randomized and received at least one dose of study drug;~2. ≥ 80% treatment compliance;~3. Last daily dose of study drug administered on the same date that ABPM was initiated at Week 8/End of Study or early termination (EOS);~4. ≥ 23.5 hours of ABPM data at baseline and at Week 8/EOS or early termination, and ≥ 75% ABPM readings;~5. No major protocol deviation that impacted ABPM readings.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| VI-0521 Top Dose (Phentermine 15 mg + Topiramate 92 mg) | Mean Change in Systolic and Diastolic Blood Pressure From Baseline to Week 8 as Measured in Clinic | Systolic blood pressure as measured in clinic | -4.3 mmHg | Standard Error 1.15 |
| VI-0521 Top Dose (Phentermine 15 mg + Topiramate 92 mg) | Mean Change in Systolic and Diastolic Blood Pressure From Baseline to Week 8 as Measured in Clinic | Diastolic blood pressure as measured in clinic | -1.3 mmHg | Standard Error 0.82 |
| Phentermine 30mg | Mean Change in Systolic and Diastolic Blood Pressure From Baseline to Week 8 as Measured in Clinic | Systolic blood pressure as measured in clinic | -1.2 mmHg | Standard Error 1.13 |
| Phentermine 30mg | Mean Change in Systolic and Diastolic Blood Pressure From Baseline to Week 8 as Measured in Clinic | Diastolic blood pressure as measured in clinic | 1.0 mmHg | Standard Error 0.81 |
| Placebo | Mean Change in Systolic and Diastolic Blood Pressure From Baseline to Week 8 as Measured in Clinic | Systolic blood pressure as measured in clinic | -1.7 mmHg | Standard Error 1.12 |
| Placebo | Mean Change in Systolic and Diastolic Blood Pressure From Baseline to Week 8 as Measured in Clinic | Diastolic blood pressure as measured in clinic | -1.1 mmHg | Standard Error 0.8 |
Comparison: In-clinic systolic blood pressurep-value: 0.0109ANCOVA
Comparison: In-clinic systolic blood pressurep-value: 0.0339ANCOVA
Comparison: In-clinic systolic blood pressurep-value: 0.6769ANCOVA
Comparison: In-clinic diastolic blood pressurep-value: 0.0082ANCOVA
Comparison: In-clinic diastolic blood pressurep-value: 0.8131ANCOVA
Comparison: In-clinic diastolic blood pressurep-value: 0.015ANCOVA