Mycoses, Obesity
Conditions
Keywords
Echinocandin, Obesity, Pharmacokinetics, Pharmacodynamics, Fungal infection
Brief summary
This study will find how weight affects the dosing of a drug called anidulafungin. Currently, the amount of anidulafungin a patient receives is the same regardless of the patient's weight. BMI groups were for enrollment purposes only and not used for ordinal data analysis.
Detailed description
This study is designed to measure drug concentrations in the blood of volunteers administered a single intravenous dose of anidulafungin. The volunteers to be enrolled will not have either candidiasis or any other fungal infection. This is a single center study. Up to a total of 35 adult volunteers will be consented for the study at the Clinical and Translational Research Center (CTRC). Eighteen of these volunteers are needed to complete the study. The others will likely be screen failures, which is more likely in the BMI \> 40 kg/m2 group. Volunteers will be admitted to the CTRC for an overnight stay. Half will be female and half male. Six volunteers will have a body mass index (BMI) less than 25 kg/m2, six will have a BMI 25-40 kg/m2, and six will have a BMI greater than 40 kg/m2. \*\* BMI groups will only be used for patient enrollment and not for data analysis. total body weight will be used as a continuous variable for data analysis. \*\* Volunteers will have height and weight measured after they have consented to participate. All volunteers in each category will receive a single dose of intravenous anidulafungin of 100 mg. The volunteers will have blood drawn via an intravenous catheter just prior to the dose, and then at 1.5, 8, 16, and 24h after the drug dose. The intravenous catheter is then removed after the 24h blood draw, and the volunteer discharged from the study. The volunteer will be asked to return to the CTRC outpatient center at 48 and 72 hours to have the final 2 blood draws conducted. Subjects who are excluded from study participation due to their laboratory results will be provided with a copy of their results and an explanation of the reason for ineligibility.
Interventions
DRUGAnidulafungin
Anidulafungin 100 mg IV (each volunteer will only receive one dose of the study drug)
Sponsors
National Center for Research Resources (NCRR)
University of Texas Southwestern Medical Center
Texas Tech University Health Sciences Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Male and female subjects, age \> 18 years old, of all racial and ethnic origins. * Non-English-speaking Spanish speakers will be included in the study. * The investigators are recruiting six normal or underweight (BMI \< 25 kg/m2), six overweight or obese (BMI 25-40 kg/m2), and six extremely obese (BMI \> 40 kg/m2) for this study. This index is calculated using the volunteer's height and weight (Formula: weight (lb) / \[height (in)\]2 x 703). Half of each group will be male; the other half will be female.
Exclusion criteria
* Pregnant or nursing or unwilling to use a reliable contraception method during the study. The effects of anidulafungin on pregnancy are unknown. In addition, the metabolic changes that accompany pregnancy may alter the concentration-time profile of anidulafungin, so that the pregnancy and postpartum state would be a confounding variable. * Abnormal liver function tests: transaminases \> 3 times upper limit of normal, Alkaline phosphatase \> 3 times upper limit of normal, total bilirubin \> 3 times upper limit of normal. * History of allergies to echinocandins. * Echinocandins are contraindicated for any reason. * Volunteers unwilling to comply with study procedures. * Suspected or documented systemic fungal infection. * Concomitant use of rifamycins, tacrolimus, or cyclosporine. * Current participation or previous participation within 28 days of enrollment in another research study that involves the use of medication, contrast, or any other compound that may alter blood count and/or blood chemistry (liver function, kidney function or electrolyte balance) (Unless waved by PI). * Donation of 450mL (one unit) of blood or more within 8 weeks (56 days) prior to study enrollment (Unless waved by PI). * Creatinine Clearance \< 70 ml/min as estimated by the Cockcroft-Gault equation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Serum Clearance of Anidulafungin | 0-72 hours | How quickly the body eliminates anidulafungin after a single dose |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Anidulafungin Six volunteers will have a body mass index (BMI) less than 25 kg/m2, 6 will have a BMI 25-40 kg/m2, and 6 will have a BMI greater than 40 kg/m2.
Anidulafungin: Anidulafungin 100 mg IV (each volunteer will only receive one dose of the study drug) | 18 |
| Total | 18 |
Baseline characteristics
| Characteristic | Anidulafungin |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 17 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 11 Participants |
| Region of Enrollment United States | 18 participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 2 / 20 |
| serious Total, serious adverse events | 0 / 20 |
Outcome results
Primary
Serum Clearance of Anidulafungin
How quickly the body eliminates anidulafungin after a single dose
Time frame: 0-72 hours
Population: Noncompartmental analysis of anidulafungin clearance
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Anidulafungin | Serum Clearance of Anidulafungin | 0.94 L/hr |