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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Morbid Obesity

Intervention / Treatment
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* Drug: Administration of study drug


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient has a BMI ≥40 kg/m2 and is undergoing bariatric surgery Subject is at least 18 of age on the day of screening. Subject or legal representatives are able and willing to sign the Informed Consent before screening evaluations. Exclusion Criteria: Documented history of sensitivity to medicinal products or excipients similar to those found in the polyene preparation. History of, or current abuse of drugs, alcohol or solvents (up until a maximum of three months before enrolment). Inability to understand the nature of the trial and the procedures required. Administration of nephrotoxic medication (aminoglycosids, immunosuppressants, antivirals, antineoplastic agents) up until a maximum of one month before enrolment.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AmBisome, Liposomal amphotericin B, Pharmacokinetics, Obesity, Bariatric surgery