Primary objective:To determine the effect of obesity (BMI > 35 kg/m2) on the pharmacokinetics of posaconazole and develop a dosing regimen for obese patients. Secondary objective:• To describe the pharmacokinetics of the augmented dose of 400 in…
ID
Source
Brief title
Condition
- Fungal infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
A farmacokinetic model using Non Linear Mixed Effects Modelling (NONMEM). Model
validation using bootstrap
method. The final model will be used for Monte Carlo simulation for
multiple-dosing regimens and higher dosages.
Secondary outcome
NA
Background summary
The prevalence of obesity in adults and children is rapidly increasing across
the world. Pharmacokinetic studies are necessary to determine the appropriate
dosing regimen, as obesity and morbid obesity are associated with many
physiological changes affecting pharmacokinetics.
Although posaconazole is approved for the prophylaxes and treatment of invasive
fungal infections, specific dosing guidelines for posaconazole in (morbidly)
obese patients are not specified [1]. There is clear evidence indicating that
heavier patients are receiving a sub-optimal dose if the current guidelines are
used [2]. Specifically in the setting of augmented prevalence of species with
intermediate susceptible to posaconazole, adequate dosing is needed at start of
treatment.
Therefore it seems prudent to conduct a trial in a cohort of obese patients who
receive posaconazole (300mg or 400mg) and define the pharmacokinetics. These
will then be compared to the pharmacokinetics in a normal-weight group
receiving 300mg posaconazole.
This study aims to provide clinical information that will be used to compare
with non-obese patients and determine an optimal dosing strategy thru modeling
and simulation.
Study objective
Primary objective:
To determine the effect of obesity (BMI > 35 kg/m2) on the pharmacokinetics of
posaconazole and develop a dosing regimen for obese patients.
Secondary objective:
• To describe the pharmacokinetics of the augmented dose of 400 in obese
patients;
Study design
Prospective, open-label, non-randomized, multi-center, single-dose dose
escalation trial.
Intervention
Placing a venous cathether for blood sampling.
Single dose of posaconazol, adminstered according to SPC.
Sampling of a total of 60ml blood (including, PK curve, lab and hematology)
Study burden and risks
The risk-classification is assessed as negligible to the patient population
receiving study drug at the current regimen. The drug is licensed on the Dutch
market for the 300 dosages administered in this trial. Although the 400mg dose
in obese is not a registered dose but we expect similar exposure in this group
compared to non-obese, based on the study of Miceli et al 2015 [2]. The
medication will be administered as a single dose only and posaconazole is
considered to be safe. Therefore ,there is no attributable risk for the
application of the study protocol to the subjects.
Geert Grooteplein 10
Nijmegen 6525GA
NL
Geert Grooteplein 10
Nijmegen 6525GA
NL
Listed location countries
Age
Inclusion criteria
1. Subjects BMI:
o obese groups: subject must have a BMI >=35 kg/m2 at the time of inclusion,
o non-obese group: subject must have a BMI >=18.5 and < 25kg/m2 at the time of inclusion.;2. Subject is at least 18 years of age on the day of screening and not older than 65 years of age on the day of dosing;
3. If a woman, is neither pregnant nor able to become pregnant and is not nursing an infant;;4. Subject is able and willing to sign the Informed Consent before screening evaluations.
For the non-obese subjects the following additional inclusion criteria applies:
5. Subject is in good age-appropriate health condition as established by medical history, physical examination, electrocardiography, results of biochemistry, hematology and urinalysis testing within 6 weeks prior to study drug administration. Results of biochemistry, hematology and urinalysis testing should be within the laboratory's reference ranges (see Appendix A). If laboratory results are not within the reference ranges, the subject is included based on the investigator*s judgment that the observed deviations are not clinically relevant. This should be clearly recorded;
Exclusion criteria
1. Documented history of sensitivity to medicinal products or excipients similar to those found in the posaconazole preparation;
2. History of, or known abuse of drugs, alcohol or solvents (up until a maximum of three months before study drug administration);
3. Use of medication that has known relevant interaction with study drug as determined by the investigator up to 1 weeks prior to study drug administration.
4. Donation of blood or plasma to a blood bank or in a clinical study (except a screening visit) within 4 weeks prior to study drug administration;
5. Blood transfusion within 8 weeks prior to study drug administration;
6. Any other sound medical, psychiatric and/or social reason as determined by the investigator.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
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Other (possibly less up-to-date) registrations in this register
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In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2017-002916-14-NL |
| CCMO | NL59354.100.17 |