Effect of VI-0521 (Qsymia®) on Glomerular Filtration Rate (GFR) in Overweight or Obese Healthy Subjects

Study Overview
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Brief Summary
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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
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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).

Official Title
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A Phase IV, Single-Center, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Effect of VI-0521 on the Glomerular Filtration Rate of Healthy Overweight or Obese Subjects

Conditions
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Obesity

Intervention / Treatment
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* Drug: Qsymia
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VI-0521 (Qsymia)<br>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) | Drug: Qsymia<br> <br> * Other names: Phentermine and Topiramate ER (Extended Release);|
| Placebo Comparator: Sugar pill<br>Days 1-28: Placebo | Drug: Placebo<br> <br> * Other names: Sugar Pill;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline, end of treatment | 
| 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 | Baseline, 28 days after end of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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VI-0521, Healthy volunteers, Renal function, Glomerular Filtration Rate, Kidney function, Qsymia, Iohexol, Serum Creatinine, Creatinine clearance, Renal Clearance