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

Condition(s) targeted: Obesity

Intervention: Qsymia (Drug)

Phase: Phase 4

Status: Completed

Sponsored by: VIVUS, Inc.

Official(s) and/or principal investigator(s):
Chris Galloway, MD, Principal Investigator

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.

Official title: 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

Study design: Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Primary outcome: Change in iohexol clearance from baseline to end of treatment and change from baseline to 28 days after end of treatment

Secondary outcome:

Change in serum creatinine from baseline to end of treatment and change from baseline to 28 days after end of treatment

Change in cystatin C from baseline to end of treatment and change from baseline to 28 days after end of treatment

Proportion of subjects with a decrease of >/= 15% in iohexol clearance from baseline to end of treatment

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).

Minimum age: 18 Years. Maximum age: 65 Years. Gender(s): Both.

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

Research Center, Lakewood, Colorado 80228, United States

Starting date: August 2014
Last updated: January 9, 2015