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

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

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.

Study Overview

• Status: Completed
• Conditions: Obesity
• Intervention / Treatment: Drug: Placebo; Drug: Qsymia

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).

• Study Type: Interventional
• Enrollment (Actual): 51
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Lakewood, Colorado, United States, 80228
      • Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: VIVUS LLC
• Investigators: Principal Investigator: Chris Galloway, MD

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2014
• Primary Completion (Actual): November 1, 2014
• Study Completion (Actual): November 1, 2014

Study Registration Dates

• First Submitted: August 26, 2014
• First Submitted That Met QC Criteria: August 27, 2014
• First Posted (Estimate): September 1, 2014

Study Record Updates

• Last Update Posted (Actual): November 7, 2017
• Last Update Submitted That Met QC Criteria: October 6, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: Healthy volunteers; Iohexol; Renal function; Kidney function; Serum Creatinine; Glomerular Filtration Rate; Qsymia; VI-0521; Creatinine clearance; Renal Clearance
• Additional Relevant MeSH Terms: Body Weight; Overweight; Hypoglycemic Agents; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Anticonvulsants; Appetite Depressants; Anti-Obesity Agents; Central Nervous System Stimulants; Sympathomimetics; Topiramate; Phentermine
• Other Study ID Numbers: OB-404