Effect of Weight and/or Obesity on Ethambutol Drug Concentrations

Obesity Clinical Trial

Official title:

Population Pharmacokinetics Analysis of Ethambutol in Overweight and Obese Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01048697
• Other study ID #: TTUHSC 030032
• Secondary ID: 5UL1RR024982-02
• Status: Completed
• Phase: Phase 4
• First received: January 12, 2010
• Last updated: January 23, 2013
• Start date: January 2010
• Est. completion date: December 2010

Study information

• Verified date: January 2013
• Source: Texas Tech University Health Sciences Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

This study is designed to measure drug concentrations in the blood of healthy volunteers administered a single dose of ethambutol. Our hypothesis is that volunteers with a body mass index (BMI) 25-40 kg/m2 will remove ethambutol more quickly from the blood than leaner volunteers, and those with a BMI > 40 kg/m2 will have even greater clearance than those who are leaner.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: December 2010
• Est. primary completion date: December 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Male and female volunteers, age 18 years of age or older, of all racial and ethnic origins. English and/or Spanish speaking volunteers are eligible to participate.

• We are recruiting 6 normal weight (BMI <25 kg/m2), 6 obese (BMI 25-40 kg/m2), and 6 extremely obese (BMI > 40 kg/m2) for this study. Half of each group will be male, the other half will be female.

Exclusion Criteria:

• Creatinine clearance < 70 ml/min as estimated by the Cockcroft-Gault equation.

• Pregnant or nursing or unwilling to use a reliable contraception method during the study period. The effects of ethambutol on pregnancy are unknown. In addition, the metabolic changes that accompany pregnancy may alter the concentration-time profile of ethambutol, so that the pregnancy and post-partum state would be a confounding variable.

• Abnormal liver function tests: transaminases >10 time the upper limit of normal, alkaline phosphatase > 5 time the upper limit of normal, total bilirubin >5 time the upper limit of normal.

• History of allergy to ethambutol.

• Ethambutol is contraindicated for any reason.

• Suspected or documented mycobacterial infection.

• History of gout.

Study Design

Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Obesity
• Tuberculosis

Intervention

Drug:
• Ethambutol
All volunteers in each category will receive a single dose of oral ethambutol based on American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of American (ATS/CDC/IDSA) TB treatment guidelines.1 We will not use any doses higher than the maximum dose recommended for daily administration by the current ATS/CDC/IDSA TB guidelines (which use ideal body weight for dosing): 40-55kg: 800 mg (two 400 mg tablets) 56-75kg: 1,200 mg (three 400 mg tablets) 76-90kg: 1,600 mg (four 400 mg tablets) > 90 kg: No dosage recommendations so these volunteers will only receive 1,600 mg (four 400 mg tablets)

Locations

Country	Name	City	State
United States	University of Texas Southwestern Medical Center	Dallas	Texas

Sponsors (3)

Lead Sponsor	Collaborator
Texas Tech University Health Sciences Center	National Center for Research Resources (NCRR), University of Texas Southwestern Medical Center

Country where clinical trial is conducted

United States, 

References & Publications (1)

Hall RG 2nd, Swancutt MA, Meek C, Leff RD, Gumbo T. Ethambutol pharmacokinetic variability is linked to body mass in overweight, obese, and extremely obese people. Antimicrob Agents Chemother. 2012 Mar;56(3):1502-7. doi: 10.1128/AAC.05623-11. Epub 2011 De — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Total Clearance of Ethambutol		Blood samples will be collected over a 24 hour period (0, 2, 6, 11, 18, and 24 hours)	No