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

Phase 4

Completed

• Conditions: Morbid Obesity
• Interventions: Drug: Administration of study drug

• Registration Number: NCT02320604
• Lead Sponsor: Radboud University Medical Center

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.

Study Timeline

• Study First Submitted: 2014-10-31
• Study First Submitted QC: 2014-12-15
• Study First Posted: 2014-12-19
• Study Start: 2018-03-22
• Primary Completion: 2018-11-03
• Study Completion: 2018-11-03
• Status Verified: 2019-01
• Last Update Submitted: 2020-10-16
• Last Update Posted: 2020-10-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 16

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Obese Subjects 1mg/kg	Administration of study drug	8 obese subjects will receive 1mg/kg Ambisome i.v. infused over 45 minutes
Obese Subjects 2mg/kg	Administration of study drug	8 obese subjects will receive 2mg/kg Ambisome i.v. infused over 90 minutes

Primary Outcome Measures

Name	Time	Method
Area Under Curve (AUC) 0-inf Ambisome	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	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.

Secondary Outcome Measures

Name	Time	Method
Peak Plasma Concentration (Cmax) Ambisome	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	Peak concentration over the sampling interval.

Trial Locations

Locations (2)

St. Antonius hospital; 🇳🇱 Nieuwegein, Netherlands

Radboud University Medical Center; 🇳🇱 Nijmegen, Gelderland, Netherlands