Anidulafungin Pharmacokinetics Given as a Single Intravenous Dose to Obese Patients (ADOPT)

Obesity Morbid Clinical Trial

— ADOPT  

Official title:

Pharmacokinetics of Anidulafungin (Ecalta ®) Given Intravenously as Prophylaxis to Obese Patients With Risk of Invasive Fungal Infection Undergoing Gastric Bypass Surgery.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02021123
• Other study ID #: UMCN-AKF 13.06
• Status: Completed
• Phase: Phase 4
• Start date: August 2014
• Est. completion date: October 2014

Study information

• Verified date: November 2020
• Source: Radboud University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Because anidulafungin is generally well tolerated and appears to have limited interaction with other drugs, it is a potential important agent in the treatment of invasive fungal infections. Although anidulafungin is approved for the treatment of invasive candidiasis in adult non-neutropenic patients, dosing guidelines for anidulafungin in (morbidly) obese patients are not available. Subsequently, the pharmacokinetic profile of anidulafungin (as well as other echinocandins) in this specific patient population is still largely unknown. During endoscopic gastric bypass surgery, patients are more prone to various kinds of infection, justifying the prophylactic use of anidulafungin in this specific cohort of patients.

To build a valid pharmacokinetic model, obese patients with a BMI ≥ 40 undergoing endoscopic gastric bypass surgery will receive a single dose of 100 mg anidulafungin (besides standard anti-bacterial prophylaxis) and a PK-curve will be drawn. These PK-values can then be compared to the pharmacokinetics in a normal-weight group.

Description:

All obese patients with a BMI ≥ 40 kg/m2 undergoing endoscopic gastric bypass surgery who receive a prophylactic single dose of 100 mg anidulafungin will be included in the analysis. A PK curve will be determined after administration of anidulafungin at t=0.5, 1, end of infusion, 2, 4, 6, 8, 10, 12, 24, and 48 and (if feasible) 72 hours post infusion (n=12 samples). Blood samples (4 mL) on PK days will be taken to obtain at least 2.0 mL of plasma.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: October 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Patient has a BMI =40 kg/m2 and is undergoing endoscopic gastric bypass surgery.

2. Subject is at least 18 years of age on the day of screening.

3. If subject is female: neither pregnant, nor able to become pregnant and is not nursing an infant.

4. Subject or legal representatives are able and willing to sign the Informed Consent before screening evaluations.

Exclusion Criteria:

1. Documented history of sensitivity to medicinal products or excipients similar to those found in the echinocandin preparation.

2. History of, or current abuse of drugs, alcohol or solvents.

3. Inability to understand the nature of the trial and the procedures required.

Related Conditions & MeSH terms

• Obesity Morbid
• Obesity, Morbid

Intervention

Drug:
• Anidulafungin 100mg single dose iv
Anidulafungin 100mg single dose iv pre-surgery (gastric bypass)

Locations

Country	Name	City	State
Netherlands	St. Antonius hospital	Nieuwegein
Netherlands	Radboud University Medical Center	Nijmegen	Gelderland

Sponsors (1)

Lead Sponsor	Collaborator
Radboud University

Country where clinical trial is conducted

Netherlands, 

References & Publications (1)

Lempers VJ, van Rongen A, van Dongen EP, van Ramshorst B, Burger DM, Aarnoutse RE, Knibbe CA, Brüggemann RJ. Does Weight Impact Anidulafungin Pharmacokinetics? Clin Pharmacokinet. 2016 Oct;55(10):1289-1294. doi: 10.1007/s40262-016-0401-8. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	adverse events	adverse events will be collected and reported	0-72 h after dosing
Primary	anidulafungin area under the curve	The primary outcome measurement will be the area under the plasma concentration-time curve (AUC) from time 0 to infinitive (inf) post infusion (AUC0- inf) value of anidulafungin. This will be determined by use of the log-linear trapezoidal rule. Peak plasma concentrations (Cmax) will be directly observed from the data. The elimination rate constant will be determined by linear regression of the terminal points of the log-linear plasma concentration time curve. Clearance (CL) will be calculated as dose/AUC0- inf.	0-72 h after single dose
Secondary	Predict long-term exposure after repeated dosing by using a pharmacokinetic model of anidulafunign in obese patients by using AUC(0-inf), Cmax, elimination half-life and clearance.	Simulate pharmacokinetics of anidulafungin after obtaining all plasma concentrations using modeling software to predict long-term exposure. For this, area under the plasma concentration-time curve (AUC) from time 0 to infinitive (inf) post infusion (AUC0- inf), peak plasma concentration (Cmax), elimination half-life and clearance values of anidulafungin will be used (as calculated in outcome measure 1). The PK curve of day 1-3 will serve to calculate these values.	PK curve on day 1-3