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

• ClinicalTrials.gov Identifier: NCT02229214
• Recruitment Status: Completed
• First Posted: September 1, 2014
• Results First Posted: February 9, 2016
• Last Update Posted: November 7, 2017
• Sponsor: VIVUS LLC
• Information provided by (Responsible Party): VIVUS LLC

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Obesity	Drug: Qsymia; Drug: Placebo	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 51 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: August 2014
• Actual Primary Completion Date: November 2014
• Actual Study Completion Date: November 2014

Arms and Interventions

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 Name: Sugar Pill

Outcome Measures

Primary Outcome Measures :

1. Change in iGFR (Glomerular Filtration Rate as Measured by Iohexol Clearance) From Baseline to End of Treatment [ Time Frame: 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.

2. Change in iGFR (Glomerular Filtration Rate as Measured by Iohexol Clearance) From Baseline to 28 Days After End of Treatment [ Time Frame: 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 :

1. Change in Serum Creatinine From Baseline to End of Treatment [ Time Frame: Baseline, end of treatment ]
2. Change in Serum Creatinine From Baseline to 28 Days After End of Treatment [ Time Frame: Baseline, 28 days after end of treatment ]
3. Change in Cystatin C From Baseline to End of Treatment [ Time Frame: Baseline, end of treatment ]
4. Change in Cystatin C From Baseline to 28 Days After End of Treatment [ Time Frame: Baseline, 28 days after end of treatment ]
5. Percentage of Subjects With a Decrease of >/= 15% in Iohexol Clearance From Baseline to End of Treatment [ Time Frame: Baseline, end of treatment ]
6. 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 ]

Eligibility Criteria

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

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

Contacts and Locations

Locations

United States, Colorado

Research Center

Lakewood, Colorado, United States, 80228

Sponsors and Collaborators

VIVUS LLC

Investigators

• Principal Investigator: Chris Galloway, MD

More Information

• Responsible Party: VIVUS LLC
• ClinicalTrials.gov Identifier: NCT02229214
• Other Study ID Numbers: OB-404
• First Posted: September 1, 2014
• Results First Posted: February 9, 2016
• Last Update Posted: November 7, 2017
• Last Verified: October 2017

Keywords provided by VIVUS LLC:

Renal function; Glomerular Filtration Rate; Kidney function; Qsymia; Iohexol; Serum Creatinine; Creatinine clearance; Renal Clearance; VI-0521; Healthy volunteers

Additional relevant MeSH terms:

Overweight; Body Weight; Topiramate; Phentermine; Anticonvulsants; Hypoglycemic Agents; Physiological Effects of Drugs; Central Nervous System Stimulants; Appetite Depressants; Anti-Obesity Agents; Sympathomimetics; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action