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Dosing Obese With Noxafil® Under a Trial (DONUT) (DONUT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03246386
Recruitment Status : Completed
First Posted : August 11, 2017
Last Update Posted : October 19, 2020
Sponsor:
Collaborators:
St. Antonius Hospital
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Radboud University

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.


Condition or disease Intervention/treatment Phase
Morbid Obesity Drug: Posaconazole Injection [Noxafil] 300mg Drug: Posaconazole Injection [Noxafil] 400mg Phase 4

Detailed Description:
Obese patients with a BMI ≥ 35 kg/m2 undergoing endoscopic gastric bypass surgery will receive a 300 mg or 400mg dose of posaconazole. A PK curve will be determined after administration at t=0.45, 0.75, 1, 1.5, 2, 4, 8, 12, 24, and (if feasible) 48 hours post infusion. Blood samples (4 mL) on PK days will be taken to obtain at least 2.0 mL of plasma.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Comparing a 2 groups of obese subjects vs 1 group of non-obese subjects.
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Pharmacokinetics of Posaconazole Given as a Single Intravenous Dose to Obese Subjects: Dosing Obese With Noxafil® Under a Trial (DONUT)
Actual Study Start Date : November 5, 2017
Actual Primary Completion Date : September 1, 2018
Actual Study Completion Date : September 1, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Obese subjects
Subjects with a BMI>35 kg/m2
Drug: Posaconazole Injection [Noxafil] 300mg
Single dose by intravenous infusion 300mg

Drug: Posaconazole Injection [Noxafil] 400mg
Single dose by intravenous infusion 400mg

Active Comparator: Non-obese subjects
Subjects with a BMI>18.5 and <25 kg/m2
Drug: Posaconazole Injection [Noxafil] 300mg
Single dose by intravenous infusion 300mg




Primary Outcome Measures :
  1. Posaconazole exposure [ Time Frame: Through study completion (usually after 24 or 48 hours) ]
    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).


Secondary Outcome Measures :
  1. Exposure with augemented posaconazol dose [ Time Frame: Through study completion (usually after 24 or 48 hours) ]
    The concentration-time curve of posaconazole in obese receiving 400mg will be compared with that in non-obese subjects. Exposure is assessed by Area-Under-the-Curve from zero to 48 hours (AUC0-48h).



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Subjects BMI:

    • obese groups: subject must have a BMI ≥35 kg/m2 at the time of inclusion,
    • non-obese group: subject must have a BMI ≥18.5 and < 25kg/m2 at the time of inclusion.
  2. 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;
  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;

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03246386


Locations
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Netherlands
St. Antonius hospital
Nieuwegein, Netherlands
Radboudumc
Nijmegen, Netherlands
Sponsors and Collaborators
Radboud University
St. Antonius Hospital
Merck Sharp & Dohme Corp.
Investigators
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Principal Investigator: Roger Brüggemann, PhD-PharmD Radboud University
Additional Information:
paper  This link exits the ClinicalTrials.gov site

Publications of Results:
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Responsible Party: Radboud University
ClinicalTrials.gov Identifier: NCT03246386    
Other Study ID Numbers: UMCN-AKF-17.08
First Posted: August 11, 2017    Key Record Dates
Last Update Posted: October 19, 2020
Last Verified: December 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Obesity, Morbid
Obesity
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Posaconazole
Antifungal Agents
Anti-Infective Agents
Trypanocidal Agents
Antiprotozoal Agents
Antiparasitic Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs