Morbid ObesityPhase 4DONUTNCT03246386

Dosing Obese With Noxafil® Under a Trial (DONUT)

A Phase 4 study testing Posaconazole Injection [Noxafil] 300mg and Posaconazole Injection [Noxafil] 400mg in people with Morbid Obesity, run by Radboud University Medical Center at 2 sites in Netherlands.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for: Morbid Obesity
What is being tested?: Posaconazole Injection [Noxafil] 300mg and Posaconazole Injection [Noxafil] 400mg
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 24 participants
Where: 2 sitesNetherlands
Study dates: 5 Nov 2017to 1 Sep 2018
Phase: Phase 4
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

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.
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.
For the non-obese subjects the following additional inclusion criteria applies:
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;

Who cannot join

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;

Trial locations and contacts

2 sites in 1 country.

Netherlands2 sites

St. Antonius hospital
Nieuwegein
Radboudumc
Nijmegen

Other trials in Netherlands

About this study

Official title: Pharmacokinetics of Posaconazole Given as a Single Intravenous Dose to Obese Subjects: Dosing Obese With Noxafil® Under a Trial (DONUT)

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.

Read the 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.

Conditions: Morbid Obesity
Being tested: Posaconazole Injection [Noxafil] 300mg, Posaconazole Injection [Noxafil] 400mg
Medical subject headings: Obesity, Morbid

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Posaconazole Injection [Noxafil] 300mgDrug
Single dose by intravenous infusion 300mg
Posaconazole Injection [Noxafil] 400mgDrug
Single dose by intravenous infusion 400mg

Study groups in NCT03246386
Study group	Role	What they receive
Obese subjects	Experimental	Subjects with a BMI>35 kg/m2 Receives: 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 Receives: Drug: Posaconazole Injection [Noxafil] 300mg

What is being measured

The primary outcome is the main question the study is designed to answer.

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).
Measured: Through study completion (usually after 24 or 48 hours)

Secondary outcomes (1)

Exposure with augemented posaconazol dose
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).
Measured: Through study completion (usually after 24 or 48 hours)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

5 Nov 20171 Sep 2018

First posted11 Aug 2017
Study start5 Nov 2017
Primary completion1 Sep 2018
Study completion1 Sep 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Morbid ObesityStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Basic science
Allocation: Non-randomised
Intervention model: Parallel groups
Model description: Comparing a 2 groups of obese subjects vs 1 group of non-obese subjects.
Masking: None (open label)
Enrolment: 24 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03246386
Sponsor's protocol ID: UMCN-AKF-17.08
Acronym: DONUT
Status last verified: Dec 2019
First submitted: 2 Aug 2017
Last updated: 19 Oct 2020
Results posted: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Publications

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.
PubMed 31971567

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Morbid Obesity trials

Study at a glance

From the registry record, last updated by the sponsor on 19 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Pharmacokinetics of Posaconazole Given as a Single Intravenous Dose to Obese Subjects: Dosing Obese With Noxafil® Under a Trial (DONUT)
ClinicalTrials.gov ID: NCT03246386
Acronym / sponsor ID: DONUT / UMCN-AKF-17.08
Conditions: Morbid Obesity
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 24 participants (actual)
Lead sponsor: Radboud University Medical CenterUniversity, hospital or other
Collaborators: St. Antonius Hospital, Merck Sharp & Dohme LLC
Study start: 5 Nov 2017 (actual)
Primary completion: 1 Sep 2018 (actual)
Study completion: 1 Sep 2018 (actual)
First posted: 11 Aug 2017 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Basic science
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2
Model description: Comparing a 2 groups of obese subjects vs 1 group of non-obese subjects.

Arm	Type	Receives
Obese subjects	Experimental	Drug: Posaconazole Injection [Noxafil] 300mg, Drug: Posaconazole Injection [Noxafil] 400mgSubjects with a BMI>35 kg/m2
Non-obese subjects	Active comparator	Drug: Posaconazole Injection [Noxafil] 300mgSubjects with a BMI>18.5 and <25 kg/m2

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (8 listed)

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;

Key exclusion criteria (5 listed)

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;

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Posaconazole Injection [Noxafil] 300mgSingle dose by intravenous infusion 300mg	Drug	Non-obese subjects, Obese subjects
Posaconazole Injection [Noxafil] 400mgSingle dose by intravenous infusion 400mg	Drug	Obese subjects

Primary outcome

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).

1 secondary outcome

Exposure with augemented posaconazol dose
Time frame: Through study completion (usually after 24 or 48 hours)

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 19 Oct 2020.
Results publication: PubMed 31971567Wasmann 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.
paperLink provided by the sponsor.
Individual participant dataSharing planned: No

Related trials for Morbid Obesity

Active, not recruiting
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RecruitingPhase 3
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RecruitingPhase 4
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Roger Brüggemann, PhD-PharmD principal investigator

Radboud University Medical Center

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Posaconazole exposure (time frame: Through study completion (usually after 24 or 48 hours)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03246386, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Oct 2020.