Liposomal Amphotericin B (AmBisome) Pharmacokinetics Given as a Single Intravenous Dose to Obese Patients (ASPEN)

Pharmacokinetics of Liposomal Amphotericin B (AmBisome®) Given Intravenously to Patients Undergoing Bariatric Surgery

Dosing guidelines for liposomal amphotericin B (AmBisome) in (morbidly) obese patients are not available. Subsequently, the pharmacokinetic profile of AmBisome in this specific patient population is still largely unknown.

To build a valid pharmacokinetic model, obese patients with a BMI ≥ 40 undergoing endoscopic gastric bypass surgery will receive a single dose of 1 mg/kg or 2 mg/kg AmBisome (besides standard anti-bacterial prophylaxis) and a PK-curve will be drawn. These PK-values can then be compared to the pharmacokinetics of a normal-weight group.

Study Overview

• Status: Completed
• Conditions: Morbid Obesity
• Intervention / Treatment: Drug: Administration of study drug

Detailed Description

• The overall trial design is a prospective, open-label, non-randomized, single-centre, single-dose, multiple dose level trial, (1 mg/kg and 2 mg/kg).
• A total of sixteen patients with a BMI ≥40 kg/m2 undergoing bariatric surgery who receive a pre-surgery dose of AmBisome 1 mg/kg (n=8) or 2 mg/kg (n=8) will be enrolled.
• After enrollment of group 1 (1 mg/kg), an interim analysis on the safety of AmBisome will be performed before proceeding to group 2 (2 mg/kg).
• Infusion time and concentration of AmBisome will be 45 minutes (1 mg/kg group) and 90 minutes (2 mg/kg group)
• A PK curve will be determined after administration of a single, pre-surgery dose of AmBisome at t = 0.5, 0.75 (end of infusion group 1), 1.5 (end of infusion group 2), 2, 4, 6, 8, 10, 12, 24, 36, and 48 and (if feasible) 72 hours post infusion (n=12 samples) for group 1 (1 mg/kg), 8 patients.The PK curve of group 2 (2 mg/kg, 8 patients) will be similar to group 1, except for the t=1.5 hour sampling point, which will be end of infusion due to the infusion time of 90 minutes.
• Patients are considered to have completed the study if at least 9/11 samples of the PK curve up until 48 hours have been collected.
• Patients will be selected by the research team to have a good spread in weight bands.

• Study Type: Interventional
• Enrollment (Actual): 16
• 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 bariatric surgery
2. Subject is at least 18 of age on the day of screening.
3. 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 polyene preparation.
2. History of, or current abuse of drugs, alcohol or solvents (up until a maximum of three months before enrolment).
3. Inability to understand the nature of the trial and the procedures required.
4. Administration of nephrotoxic medication (aminoglycosids, immunosuppressants, antivirals, antineoplastic agents) up until a maximum of one month before enrolment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Obese Subjects 1mg/kg; 8 obese subjects will receive 1mg/kg Ambisome i.v. infused over 45 minutes	Drug: Administration of study drug; i.v. administration of Ambisome in two different dossages; Other Names: Ambisome
Experimental: Obese Subjects 2mg/kg; 8 obese subjects will receive 2mg/kg Ambisome i.v. infused over 90 minutes	Drug: Administration of study drug; i.v. administration of Ambisome in two different dossages; Other Names: Ambisome

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under Curve (AUC) 0-inf Ambisome	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 AmBisome. This will be determined by use of the log-linear trapezoidal rule.	at t = 0.5, 0.75, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 and (if feasible) 72 hours post infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak Plasma Concentration (Cmax) Ambisome	Peak concentration over the sampling interval.	at t = 0.5, 0.75, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 and (if feasible) 72 hours post infusion

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Investigators: Principal Investigator: Roeland E Wasmann, PharmD, PhD, Radboud University Medical Center

Publications and helpful links

General Publications

• Wasmann RE, Smit C, van Dongen EPH, Wiezer RMJ, Adler-Moore J, de Beer YM, Burger DM, Knibbe CAJ, Bruggemann RJM. Fixed Dosing of Liposomal Amphotericin B in Morbidly Obese Individuals. Clin Infect Dis. 2020 May 6;70(10):2213-2215. doi: 10.1093/cid/ciz885.

Helpful Links

• paper

Study record dates

Study Major Dates

• Study Start (Actual): March 22, 2018
• Primary Completion (Actual): November 3, 2018
• Study Completion (Actual): November 3, 2018

Study Registration Dates

• First Submitted: October 31, 2014
• First Submitted That Met QC Criteria: December 15, 2014
• First Posted (Estimate): December 19, 2014

Study Record Updates

• Last Update Posted (Actual): October 19, 2020
• Last Update Submitted That Met QC Criteria: October 16, 2020
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: Obesity; Pharmacokinetics; Bariatric surgery; AmBisome; Liposomal amphotericin B
• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity; Obesity, Morbid; Anti-Infective Agents; Antifungal Agents; Antiprotozoal Agents; Antiparasitic Agents; Liposomal amphotericin B
• Other Study ID Numbers: UMCN-AKF 14.04

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: No plan has been made. Individual researchers are welcome to request data with our group.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No