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

Phase 4

Completed

Conditions: Obesity

Interventions: Drug: Placebo
Drug: Qsymia

Registration Number: NCT02229214

Lead Sponsor: VIVUS LLC

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).

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 51

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sugar pill	Placebo	Days 1-28: Placebo
VI-0521 (Qsymia)	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)

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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
Change in Serum Creatinine 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
Change in Cystatin C 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