Dosing Obese With Noxafil® Under a Trial (DONUT)

NCT03246386 | Completed Phase 4

• 1 other identifier: UMCN-AKF-17.08
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 2

Brief Summary

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. There is clear evidence indicating that heavier patients are receiving a sub-optimal dose if the current guidelines are used. 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.

Conditions

Morbid Obesity

Outcome Measures

Primary Outcomes (1)

• Posaconazole exposure

  The concentration-time curve of posaconazole in obese will be compared with that in non-obese subjects. Exposure is assessed by Area-Under-the-Curve from zero to 48 hours (AUC0-48h).

  Through study completion (usually after 24 or 48 hours)

Secondary Outcomes (1)

• Exposure with augemented posaconazol dose

  Through study completion (usually after 24 or 48 hours)

Study Arms (2)

Obese subjects

EXPERIMENTAL

Subjects with a BMI\>35 kg/m2

Drug: Posaconazole Injection [Noxafil] 300mg; Drug: Posaconazole Injection [Noxafil] 400mg

Non-obese subjects

ACTIVE COMPARATOR

Subjects with a BMI\>18.5 and \<25 kg/m2

Drug: Posaconazole Injection [Noxafil] 300mg

Interventions

Posaconazole Injection [Noxafil] 300mg DRUG

Single dose by intravenous infusion 300mg

Non-obese subjects; Obese subjects

Posaconazole Injection [Noxafil] 400mg DRUG

Single dose by intravenous infusion 400mg

Obese subjects

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects BMI:
• Subject is at least 18 of age on the day of screening and not older than 65 years of age on the day of dosing;
• If a woman, is neither pregnant nor able to become pregnant and is not nursing an infant;
• Subject is able and willing to sign the Informed Consent before screening evaluations.
• 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;

You may not qualify if:

• Documented history of sensitivity to medicinal products or excipients similar to those found in the posaconazole preparation;
• History of, or known abuse of drugs, alcohol or solvents (up until a maximum of three months before study drug administration);
• 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.
• 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;
• Blood transfusion within 8 weeks prior to study drug administration;

Sponsors & Collaborators

• Radboud University Medical Center: lead
• St. Antonius Hospital: collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (2)

St. Antonius hospital

Nieuwegein, Netherlands

Location

Radboudumc

Nijmegen, Netherlands

Location

Related Publications (1)

• Wasmann RE, Smit C, van Donselaar MH, van Dongen EPA, Wiezer RMJ, Verweij PE, Burger DM, Knibbe CAJ, Bruggemann RJM. Implications for IV posaconazole dosing in the era of obesity. J Antimicrob Chemother. 2020 Apr 1;75(4):1006-1013. doi: 10.1093/jac/dkz546.

  PMID: 31971567 RESULT

Related Links

• paper

MeSH Terms

Conditions

Obesity, Morbid

Interventions

posaconazole

Condition Hierarchy (Ancestors)

Obesity; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Roger Brüggemann, PhD-PharmD

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Comparing a 2 groups of obese subjects vs 1 group of non-obese subjects.

Study Record Dates

• First Submitted: August 2, 2017
• First Posted: August 11, 2017
• Study Start: November 5, 2017
• Primary Completion: September 1, 2018
• Study Completion: September 1, 2018
• Last Updated: October 19, 2020

Record last verified: 2019-12

Data Sharing

• IPD Sharing: Will not share

Locations

NL (2)