Obesity
Conditions
Keywords
Renal function, Glomerular Filtration Rate, Kidney function, Qsymia, Iohexol, Serum Creatinine, Creatinine clearance, Renal Clearance, VI-0521, Healthy volunteers
Brief summary
The main purpose of this study is measure the effect of VI-0521 on kidney function. Specifically, glomerular filtration rate (GFR) will be measured at baseline, after 4 weeks of study treatment, and after an additional 4 weeks of off-treatment recovery.
Detailed description
This is a randomized, double-blind, placebo-controlled, single-site study in healthy overweight or obese male and female volunteers. Oral VI-0521 (combination of phentermine and topiramate \[PHEN/TPM\] extended-release capsule) will be administered daily as follows: * Days 1-3: PHEN/TPM 3.75 mg /23 mg * Days 4-6: PHEN/TPM 7.5 mg /46 mg * Days 7-9: PHEN/TPM 11.25 mg /69 mg * Days 10-28: PHEN/TPM 15 mg /92 mg A single dose of Iohexol (a non-radioactive iodine-containing contrast agent) will be administered intravenously on three separate occasions. The study will include a total of 50 healthy subjects (40 active and 10 placebo), all of whom will have overnight stays on 3 separate occasions. Total study duration is approximately 10 weeks (2 weeks screening, 4 weeks study treatment, 4 weeks post treatment follow up).
Interventions
DRUGQsymia
DRUGPlacebo
Sponsors
VIVUS LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
Key Inclusion Criteria: * Male or female 18 - 65 years of age, medically healthy with no clinically significant screening abnormalities * BMI of ≥27 to ≤45 kg/m2 * No use of any medication (prescription, over the counter (OTC) or herbal preparations) with the exception of contraception for the entirety of the study Key
Exclusion criteria
* Allergy or hypersensitivity to radio contrast media, iodine or shellfish * Plans to significantly alter their diet through fasting, very low caloric intake, elimination of certain foods (gluten, milk, meat, etc.) or similar * Plans to undertake a significant change to physical exercise levels (i.e., initiate training for a marathon) during the study period * Consumption of a high protein diet or protein/body building meal supplementation and/or replacement. The use of any product containing creatine is strictly prohibited * History of glaucoma or increased intraocular pressure * History of bipolar disorder or psychosis, history of psychiatric hospitalization, greater than one lifetime episode of major depression, current depression of moderate or greater severity, presence or history of suicidal behavior or ideation with some intent to act on it * Cholelithiasis (gallstones) within the past 6 months * History of nephrolithiasis (kidney stones) * Evidence of any clinically significant renal, pulmonary, hepatic, psychiatric or other condition by history, physical examination or laboratory studies that, in the opinion of the investigator, would contraindicate the administration of study medications, affect compliance, interfere with study evaluations or confound the interpretation of study results as determined by the investigator * Current use of any tobacco products including cigarettes, cigars, pipes, and chewing tobacco, or nicotine replacement products (e.g., patch, gum, lozenge, etc.), or chronic use within the previous three months prior to screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in iGFR (Glomerular Filtration Rate as Measured by Iohexol Clearance) From Baseline to End of Treatment | Baseline, end of treatment | Method that uses iohexol clearance and body surface area to measure kidney function. Iohexol is an FDA-approved non-radioactive iodine-containing substance widely used in radio-imaging procedures and as a marker for the measurement of in GFR. |
| Change in iGFR (Glomerular Filtration Rate as Measured by Iohexol Clearance) From Baseline to 28 Days After End of Treatment | Baseline, 28 days after end of treatment | Method that uses iohexol clearance and body surface area to measure kidney function. Iohexol is an FDA-approved non-radioactive iodine-containing substance widely used in radio-imaging procedures and as a marker for the measurement of in GFR |
Secondary
| Measure | Time frame |
|---|---|
| Change in Serum Creatinine From Baseline to End of Treatment | Baseline, end of treatment |
| Change in Serum Creatinine From Baseline to 28 Days After End of Treatment | Baseline, 28 days after end of treatment |
| Change in Cystatin C From Baseline to End of Treatment | Baseline, end of treatment |
| Change in Cystatin C From Baseline to 28 Days After End of Treatment | Baseline, 28 days after end of treatment |
| Percentage of Subjects With a Decrease of >/= 15% in Iohexol Clearance From Baseline to End of Treatment | Baseline, end of treatment |
| Percentage of Subjects With a Decrease of >/= 15% in Iohexol Clearance From Baseline to 28 Days After End of Treatment | Baseline, 28 days after end of treatment |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| VI-0521 (Qsymia) * Days 1-3: VI-0521 (Phentermine/Topiramate 3.75 mg/23 mg)
* Days 4-6: VI-0521 (Phentermine/Topiramate 7.5 mg/46 mg)
* Days 7-9: VI-0521 (Phentermine/Topiramate 11.25 mg/69 mg)
* Days 10-28: VI-0521 (Phentermine/Topiramate 15 mg/92 mg)
Qsymia | 41 |
| Placebo Days 1-28: Placebo
Placebo (sugar pill) | 10 |
| Total | 51 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 |
| Overall Study | Withdrawal by Subject | 4 | 0 |
Baseline characteristics
| Characteristic | VI-0521 (Qsymia) | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 38.4 Years STANDARD_DEVIATION 11.07 | 37.6 Years STANDARD_DEVIATION 9.8 | 38.2 Years STANDARD_DEVIATION 10.74 |
| BMI | 33.2 Kg/m^2 STANDARD_DEVIATION 4.72 | 31.3 Kg/m^2 STANDARD_DEVIATION 2.81 | 32.8 Kg/m^2 STANDARD_DEVIATION 4.46 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 13 Participants | 3 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 28 Participants | 7 Participants | 35 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| iGFR | 95.1 mL/min/1.73m^2 STANDARD_DEVIATION 14.05 | 87.3 mL/min/1.73m^2 STANDARD_DEVIATION 9.06 | 93.6 mL/min/1.73m^2 STANDARD_DEVIATION 13.49 |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants | 1 Participants | 6 Participants |
| Race (NIH/OMB) White | 30 Participants | 8 Participants | 38 Participants |
| Region of Enrollment United States | 41 participants | 10 participants | 51 participants |
| Sex: Female, Male Female | 27 Participants | 4 Participants | 31 Participants |
| Sex: Female, Male Male | 14 Participants | 6 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 33 / 41 | 6 / 10 |
| serious Total, serious adverse events | 1 / 41 | 0 / 10 |
Outcome results
Primary
Change in iGFR (Glomerular Filtration Rate as Measured by Iohexol Clearance) From Baseline to 28 Days After End of Treatment
Method that uses iohexol clearance and body surface area to measure kidney function. Iohexol is an FDA-approved non-radioactive iodine-containing substance widely used in radio-imaging procedures and as a marker for the measurement of in GFR
Time frame: Baseline, 28 days after end of treatment
Population: The number analyzed in this outcome measure are those subjects who have both baseline and 28 days after treatment iGFR measurements.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VI-0521 (Qsymia) | Change in iGFR (Glomerular Filtration Rate as Measured by Iohexol Clearance) From Baseline to 28 Days After End of Treatment | -3.75 mL/min/1.73 m^2 | Standard Error 1.49 |
| Placebo | Change in iGFR (Glomerular Filtration Rate as Measured by Iohexol Clearance) From Baseline to 28 Days After End of Treatment | 2.34 mL/min/1.73 m^2 | Standard Error 1.34 |
Primary
Change in iGFR (Glomerular Filtration Rate as Measured by Iohexol Clearance) From Baseline to End of Treatment
Method that uses iohexol clearance and body surface area to measure kidney function. Iohexol is an FDA-approved non-radioactive iodine-containing substance widely used in radio-imaging procedures and as a marker for the measurement of in GFR.
Time frame: Baseline, end of treatment
Population: The number analyzed in this outcome measure are those subjects who have both baseline and end of treatment iGFR measurements.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VI-0521 (Qsymia) | Change in iGFR (Glomerular Filtration Rate as Measured by Iohexol Clearance) From Baseline to End of Treatment | -14.92 mL/min/1.73 m^2 | Standard Error 1.28 |
| Placebo | Change in iGFR (Glomerular Filtration Rate as Measured by Iohexol Clearance) From Baseline to End of Treatment | 1.08 mL/min/1.73 m^2 | Standard Error 2.28 |
Secondary
Change in Cystatin C From Baseline to 28 Days After End of Treatment
Time frame: Baseline, 28 days after end of treatment
Population: The number analyzed in this outcome measure are those subjects who have both baseline and 28 days after end of treatment cystatin C measurements.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VI-0521 (Qsymia) | Change in Cystatin C From Baseline to 28 Days After End of Treatment | 0.01 mg/L | Standard Error 0.01 |
| Placebo | Change in Cystatin C From Baseline to 28 Days After End of Treatment | 0.02 mg/L | Standard Error 0.01 |
Secondary
Change in Cystatin C From Baseline to End of Treatment
Time frame: Baseline, end of treatment
Population: The number analyzed in this outcome measure are those subjects who have both baseline and end of treatment cystatin C measurements.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VI-0521 (Qsymia) | Change in Cystatin C From Baseline to End of Treatment | 0.04 mg/L | Standard Error 0.01 |
| Placebo | Change in Cystatin C From Baseline to End of Treatment | 0.03 mg/L | Standard Error 0.02 |
Secondary
Change in Serum Creatinine From Baseline to 28 Days After End of Treatment
Time frame: Baseline, 28 days after end of treatment
Population: The number analyzed in this outcome measure are those subjects who have both baseline and 28 days after end of treatment serum creatinine measurements.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VI-0521 (Qsymia) | Change in Serum Creatinine From Baseline to 28 Days After End of Treatment | -0.01 mg/dL | Standard Error 0.01 |
| Placebo | Change in Serum Creatinine From Baseline to 28 Days After End of Treatment | 0.03 mg/dL | Standard Error 0.02 |
Secondary
Change in Serum Creatinine From Baseline to End of Treatment
Time frame: Baseline, end of treatment
Population: The number analyzed in this outcome measure are those subjects who have both baseline and end of treatment serum creatininine measurements
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VI-0521 (Qsymia) | Change in Serum Creatinine From Baseline to End of Treatment | 0.10 mg/dL | Standard Error 0.01 |
| Placebo | Change in Serum Creatinine From Baseline to End of Treatment | 0.03 mg/dL | Standard Error 0.03 |
Secondary
Percentage of Subjects With a Decrease of >/= 15% in Iohexol Clearance From Baseline to 28 Days After End of Treatment
Time frame: Baseline, 28 days after end of treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VI-0521 (Qsymia) | Percentage of Subjects With a Decrease of >/= 15% in Iohexol Clearance From Baseline to 28 Days After End of Treatment | 7.3 percent of participants |
| Placebo | Percentage of Subjects With a Decrease of >/= 15% in Iohexol Clearance From Baseline to 28 Days After End of Treatment | 0 percent of participants |
Secondary
Percentage of Subjects With a Decrease of >/= 15% in Iohexol Clearance From Baseline to End of Treatment
Time frame: Baseline, end of treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VI-0521 (Qsymia) | Percentage of Subjects With a Decrease of >/= 15% in Iohexol Clearance From Baseline to End of Treatment | 48.8 percent of participants |
| Placebo | Percentage of Subjects With a Decrease of >/= 15% in Iohexol Clearance From Baseline to End of Treatment | 0 percent of participants |