Clinical trial NCT02320604: Liposomal Amphotericin B (AmBisome) Pharmacokinetics Given as a Single Intravenous Dose to Obese Patients (ASPEN)
Official title: Pharmacokinetics of Liposomal Amphotericin B (AmBisome®) Given Intravenously to Patients Undergoing Bariatric Surgery
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Morbid Obesity
Keywords: Liposomal amphotericin B
AmBisome
Pharmacokinetics
Obesity
Bariatric surgery
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
First posted: 2014-12-19
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Area Under Curve (AUC) 0-inf Ambisome
timeFrame: 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 outcomes:
measure: Peak Plasma Concentration (Cmax) Ambisome
timeFrame: 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
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center
state: Gelderland
city: Nieuwegein
country: Netherlands
facility: St. Antonius hospital
Study officials:
affiliation: Radboud University Medical Center
name: Roeland E Wasmann, PharmD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.