The primary objective of this trial is as follows:• To determine the pharmacokinetics of anidulafungin administered to obese patients with a BMI >= 40 kg/m2. The secondary objective of this trial is as follows:• To simulate pharmacokinetics to…
ID
Source
Brief title
Condition
- Fungal infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary outcome measurement will be the area under the plasma concentration-
time curve (AUC) from time 0 to infinity (inf) post infusion (AUC0- inf) value
of anidulafungin. This will be determined by use of the log-linear trapezoidal
rule.
Peak plasma concentrations (Cmax) will be directly observed from the data.
The elimination rate constant will be determined by linear regression of the
terminal points of the log-linear plasma concentration time curve. Clearance
(CL) will be calculated as dose/AUC0- inf.
Secondary outcome
N/A
Background summary
The prevalence of obesity in adults and children is rapidly increasing across
the world. Several general (patho)physiological alterations associated with
obesity have been described, but the specific impact of these alterations on
drug metabolism and elimination and its consequences for drug dosing remains
largely unknown.
Whilst anidulafungin has much to offer, little is known about its
pharmacokinetic profile in the morbidly obese patient populations.
In a study of alternate dosing strategies of anidulafungin (200mg q48h)
administered to 13 patients admitted to the hematology ward for an allogeneic
haematopoietic stem cell transplant (HSCT) or intensive chemotherapy for acute
myeloid leukemia, we performed an interim simulation after the inclusion of 10
patients. Using the 2-compartement model with proportional error in Nonmem 7.2,
we identified that weight as a covariate identifies 19% of the inter-individual
variability in volume of distribution. Yet, in this cohort there were no
morbidly obese patients and in the public domain, there are no specific data
on patients in the upper weight bands (BMI >= 40).
Therefore it seems prudent to conduct a trial in a cohort of obese patients who
receive anidulafungin and define the pharmacokinetics. These can then be
compared to the pharmacokinetics in a normal-weight group. To build a valid
pharmacokinetic model, obese patients with a BMI >= 40 undergoing bariatric
surgery will receive a single dose of 100 mg anidulafungin (besides standard
anti-bacterial prophylaxis). A 100 mg dose is chosen as the reference dose
instead of the regular 200 mg loading dose. We assume a linear relation based
on the results obtained in our previous experiments. Therefore a single dose of
100 mg will be sufficient to define the PK and make simulations for other
dosing regimens. To minimize exposure to the study drug an initial trial with a
single dose is preferred. At a later stage a multiple dose pharmacokinetic
study may be performed to examine toxic effects of the drug.
Study objective
The primary objective of this trial is as follows:
• To determine the pharmacokinetics of anidulafungin administered to obese
patients with a BMI >= 40 kg/m2.
The secondary objective of this trial is as follows:
• To simulate pharmacokinetics to provide a rationale for optimal dosing
strategy in obese patients.
Study design
This is an open-label, non-randomised, single-centre, phase-IV, single-dose
trial.
Day 1: A single dose of anidulafungin 100 mg administered according to SPC
(pre-operative). Total body weight and body fat will be measured (using the
Taninta, a body composition analyzer).
An attempt will be made to have a PK curve up until sampling point t=48 h, with
an optional sample at t=72 hours. All infusion rates will be according to the
SPC label information.
Patients are considered to have completed the study if at least the PK curve up
until t=48 hours (with all samples resulting in an evaluable PK curve) has been
completed.
Intervention
Inserting indwelling venous cannula/venflon for study.
A single dose of anidulafungin 100 mg administered according to SPC
(pre-operative).
A PK curve will be determined after administration of a single, pre-operative
dose of anidulafungin at t=0.5, 1, end of infusion, 2, 4, 6, 8, 10, 12, 24, and
48 and (if feasible) 72 hours post infusion (n=12 samples). Blood samples (4
mL) on PK days will be taken to obtain at least 2.0 mL of plasma.
Study burden and risks
This is a prospective non-randomized, phase IV clinical study, which will be
performed in morbidly obese patients undergoing bariatric surgery. Due to
surgery in the upper gastrointestinal region, this specific population is more
prone to various kinds of infection including yeast infections. Thus, it seems
justified to administer a prophylactic dose of anidulafungin against candida
infections.
To determine the pharmacokinetics of anidulafungin in patients with very high
body weight, this specific patient population is ideal for conducting this PK
study. Because of the high frequency of endoscopic gastric bypass surgeries in
our study center (300-500 per year), it is expected that enrollment in this
study will be within a relative short period of time (expected time: 6 months)
compared to other cohorts. Moreover, because only a single prophylactic dose of
anidulafungin is administered, the attributable risk in this cohort of
otherwise healthy persons seems relatively lower if compared to other patients
possibly at risk of fungal infections (e.g. Intensive Care patients).
Geert Grooteplein Zuid 10
6525 GA Nijmegen 6525 GA
NL
Geert Grooteplein Zuid 10
6525 GA Nijmegen 6525 GA
NL
Listed location countries
Age
Inclusion criteria
1. Patient has a BMI >=40 kg/m2 and is undergoing bariatric surgery.
2. Subject is at least 18 years of age on the day of screening.
3. If subject is female: neither pregnant, nor able to become pregnant and is not nursing an infant.
4. 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 anidulafungin preparation.
2. History of or current abuse of drugs, alcohol or solvents.
3. Inability to understand the nature of the trial and the procedures required.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2013-004401-11-NL |
| CCMO | NL46907.091.13 |