Effect of Weight and/or Obesity on Ethambutol Drug Concentrations

NCT01048697 | Completed Phase 4 Results

• 2 other identifiers: TTUHSC 0300325UL1RR024982-02
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Obesity; Tuberculosis

Keywords

Obesity; Pharmacokinetics; Pharmacodynamics; Dose individualization; Tuberculosis

Outcome Measures

Primary Outcomes (1)

• Total Clearance of Ethambutol

  Blood samples will be collected over a 24 hour period (0, 2, 6, 11, 18, and 24 hours)

Study Arms (1)

Ethambutol

EXPERIMENTAL

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)

Drug: Ethambutol

Interventions

Ethambutol DRUG

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)

Also known as: Myambutol

Ethambutol

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Texas Tech University Health Sciences Center: lead
• National Center for Research Resources (NCRR): collaborator
• University of Texas Southwestern Medical Center: collaborator

Study Sites (1)

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Related 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 Dec 12.

  PMID: 22155817 RESULT

MeSH Terms

Conditions

Obesity; Tuberculosis

Interventions

Ethambutol

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Ethylenediamines; Diamines; Polyamines; Amines; Organic Chemicals

Results Point of Contact

• Title: Ronald Hall
• Organization: Texas Tech UHSC

ronald.hall@ttuhsc.edu

214-654-9404

Study Officials

• Ronald Hall, PharmD, MSCS

  Texas Tech University HSC

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: January 12, 2010
• First Posted: January 14, 2010
• Study Start: January 1, 2010
• Primary Completion: December 1, 2010
• Study Completion: December 1, 2010
• Last Updated: January 24, 2013
• Results First Posted: January 24, 2013

Record last verified: 2013-01

Locations

US (1)