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

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

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.

Study Overview

• Status: Completed
• Conditions: Obesity Morbid
• Intervention / Treatment: Drug: Anidulafungin 100mg single dose iv

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 4

Contacts and Locations

Study Locations

• Netherlands
  • Nieuwegein, Netherlands
    • St. Antonius Hospital
  • Gelderland
    • Nijmegen, Gelderland, Netherlands
      • Radboud University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Anidulafungin 100 mg single dose; 100 mg single dose anidulafungin pre-surgery (gastric bypass)	Drug: Anidulafungin 100mg single dose iv; Anidulafungin 100mg single dose iv pre-surgery (gastric bypass); Other Names: Ecalta

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
adverse events	adverse events will be collected and reported	0-72 h after dosing

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Investigators: Principal Investigator: Roger JM Brüggemann, PharmD, PhD, Radboud University Medical Center

Publications and helpful links

General Publications

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

Study record dates

Study Major Dates

• Study Start: August 1, 2014
• Primary Completion (ACTUAL): October 1, 2014
• Study Completion (ACTUAL): October 1, 2014

Study Registration Dates

• First Submitted: November 29, 2013
• First Submitted That Met QC Criteria: December 19, 2013
• First Posted (ESTIMATE): December 27, 2013

Study Record Updates

• Last Update Posted (ACTUAL): December 1, 2020
• Last Update Submitted That Met QC Criteria: November 26, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Prophylaxis; Gastric bypass; Anidulafungin; Yeast infection; Morbidly obese
• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity; Obesity, Morbid; Anti-Infective Agents; Antifungal Agents; Anidulafungin
• Other Study ID Numbers: UMCN-AKF 13.06