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

Morbid Obesity Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02320604
• Other study ID #: UMCN-AKF 14.04
• Status: Completed
• Phase: Phase 4
• Start date: March 22, 2018
• Est. completion date: November 3, 2018

Study information

• Verified date: January 2019
• Source: Radboud University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: November 3, 2018
• Est. primary completion date: November 3, 2018
• 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 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.

Related Conditions & MeSH terms

• Morbid Obesity
• Obesity, Morbid

Intervention

Drug:
• Administration of study drug
i.v. administration of Ambisome in two different dossages

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)

Wasmann RE, Smit C, van Dongen EPH, Wiezer RMJ, Adler-Moore J, de Beer YM, Burger DM, Knibbe CAJ, Brüggemann 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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

External Links

•   paper