A Study to Evaluate the Pharmacokinetics of VI-0521 Subjects With Renal Impairment

This study has been completed.
Sponsor:
Information provided by:
VIVUS, Inc.
ClinicalTrials.gov Identifier:
NCT00768404
First received: October 7, 2008
Last updated: November 30, 2009
Last verified: November 2009
  Purpose

VI-0521, a fixed dose combination of immediate-release (IR) phentermine and controlled-release (CR) topiramate, is in Phase III clinical development as a potential therapy for obesity. In human, both phentermine and topiramate are primarily cleared by renal excretion. The contribution of hepatic metabolism to elimination of phentermine and topiramate is not significant. Obese patients, the proposed indicated population for future treatment with VI-0521, are likely to have renal impairment. Therefore, this study is important in understanding the effect of renal impairment on the pharmacokinetics of topiramate and phentermine in subjects with renal impairment compared to subjects with normal renal function.


Condition Intervention Phase
Renal Impairment
Drug: Topirmate and Phentermine
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I, Open-Label, Parallel-Group, Single Dose, Non-Randomized Study To Compare The Pharmacokinetics Of Each Individual Component (Topiramate And Phentermine) Of The Combination Product VI-0521 In Subjects With Mild, Moderate And Severe Renal Impairment To Subjects With Normal Renal Function

Resource links provided by NLM:


Further study details as provided by VIVUS, Inc.:

Primary Outcome Measures:
  • Pharmacokinetics [ Time Frame: 9 days ] [ Designated as safety issue: No ]

Enrollment: 32
Study Start Date: October 2008
Study Completion Date: July 2009
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A Drug: Topirmate and Phentermine
A single oral dose of the combination product VI-0521 (15 mg phentermine and 92 mg topiramate) will be administered with 240 mL of water at hour 0.

Detailed Description:

This open-label, parallel-group, single dose, non-randomized study will be conducted at multiple sites in the United States in which up to 40 male and female subjects, 19-75 years of age (inclusive), with varying degrees of renal function may be enrolled and dosed to obtain at least 32 evaluable subjects (4 groups, 8 subjects per group). Subjects will report to the study site on the evening before treatment and will remain at the site until the 48-hour PK sample has been drawn (approximately 3 days). All subjects will be fasted overnight for a minimum of 8 hours before drug treatment in the morning. A single oral dose of the combination product VI-0521 (15 mg phentermine and 92 mg topiramate) will be administered with 240 mL of water at hour 0. Standard meals will be provided uniformly to all subjects at approximately 4 and 9 hours after dosing, and an evening snack will be provided approximately 12 - 13 hours after dosing. Blood samples for the determination of phentermine and topiramate concentrations in plasma will be collected at 0 (pre-dose), 1, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 36 and 48 hours post dosing. Subjects will be released from the study site following the 48-hour sample but will return to the site for PK sampling at 72, 96, 120, 144, 168 and 192 hours post dose. The severe renal impairment group will be given the option to stay at the site for the duration of the study.

  Eligibility

Ages Eligible for Study:   19 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Group 1 will consist of 8-10 males or females with normal renal function, 19-75 years of age, inclusive.

Groups 2-4 will consist of 8-10 males or females per group with varying degree of stable renal impairment

Exclusion Criteria:

A history or presence of significant cardiovascular, neurological, hematological, psychiatric, hepatic, gastrointestinal, pulmonary, endocrine, immunologic or renal disease or other condition known to interfere with the absorption, distribution, metabolism, or excretion of drugs or place the subjects at increased risk as determined by the investigator; any history of glaucoma, increased intraocular pressure, or medications to treat increased intraocular pressure; presence of cholelithiasis or cholecystitis within the last 6 months that has not been surgically treated with cholecystectomy; any history of a cardiovascular or cerebrovascular event; subjects requiring dialysis; any active malignancy except basal cell carcinoma; systolic blood pressure > 180 mm Hg or diastolic blood pressure > 100 mm Hg at screening or at check-in (2 rechecks are allowed); Hemoglobin <12.0 g/dL for Group 1 (patients with normal renal function); Hemoglobin <. 9.0 g/dL for Groups 2, 3 and 4 (patients with mild to severe renal function) positive drug/alcohol test at screening or check in; blood donation or significant blood loss within 56 days of dosing; plasma donation within 7 days of dosing. In female subjects, a positive pregnancy test at screening or check-in is exclusionary

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00768404

Locations
United States, California
Advanced Clinical Research Institute
Anaheim, California, United States, 92801
United States, Florida
Clinical Pharmacology of Miami
Miami, Florida, United States, 33014-3616
Orlando Clinical Research Center
Orlando, Florida, United States, 32809-3017
United States, Minnesota
DaVita Clinical Research
Minneapolis, Minnesota, United States, 55404
Sponsors and Collaborators
VIVUS, Inc.
Investigators
Study Director: Shiyin Yee, PhD VIVUS, Inc.
  More Information

No publications provided

Responsible Party: Wesley Day, VP Clinical, Vivus, Inc.
ClinicalTrials.gov Identifier: NCT00768404     History of Changes
Other Study ID Numbers: OB-106
Study First Received: October 7, 2008
Last Updated: November 30, 2009
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Renal Insufficiency
Kidney Diseases
Urologic Diseases
Phentermine
Central Nervous System Stimulants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Appetite Depressants
Anti-Obesity Agents
Sympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014