Fungal InfectionsPhase 1NCT01777763

Pharmacokinetics and Safety of Posaconazole Tablet in Participants at High Risk for Invasive Fungal Infections (MK-5592-065/P05615)

A Phase 1 study testing Posaconazole 200 mg and Posaconazole 300 mg in people with Fungal Infections, run by Merck Sharp & Dohme LLC.

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

Who is it for?: Ages 18 years and older
Conditions the study is for: Fungal Infections
What is being tested?: Posaconazole 200 mg and Posaconazole 300 mg
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 230 participants
Where: No sites listed yet
Study dates: Jun 2009to Feb 2012
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Body weight >34 kg (75 lb) and of any race/ethnicity
Able to swallow oral tablets whole
Anticipated (likely to develop within 3-5 days) or documented neutropenia due to chemotherapy, chemotherapy for a new diagnosis of acute myelogenous leukemia (AML), or AML in first relapse; myelodysplastic syndromes (MDS) in transformation to AML; allogeneic hematopoietic stem cell transplant (HSCT) participants in the pre-engraftment period or in the post-engraftment period if they are receiving immunosuppressive therapy for graft versus host disease

Who cannot join

Female must not be pregnant, must not intend to become pregnant
during the study, and must not be nursing
History of hypersensitivity to azoles
Moderate or severe liver dysfunction defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels greater than three times the upper limit of normal (ULN), AND a total bilirubin level greater than two times the ULN
Electrocardiogram (ECG) with corrected QTc interval greater than 500 msec
Posaconazole within 10 days before study enrollment

Show all 10Show fewer

Receipt of systemic antifungal therapy within 30 days of study enrollment for reasons other than antifungal prophylaxis
Evidence of known or suspected invasive or systemic fungal infection at baseline
Known or suspected history of Gilbert's disease
Creatinine clearance levels below 30 mL/min

About this study

Official title: Pharmacokinetics and Safety of Solid Oral Posaconazole (SCH 56592) in Subjects at High Risk for Invasive Fungal Infections (Phase 1b; Protocol No. P05615)

The purpose of this study is to collect pharmacokinetic (PK) information related to how well posaconazole tablet is distributed in the body and to determine the safety of this new formulation. The study consists of a Phase 1B study that includes participants with neutropenia undergoing chemotherapy for acute myelogenous leukemia (AML) or myelodysplasia (MDS) and a Phase 3 study that includes participants who are undergoing chemotherapy for AML or MDS and participants who are recipients of allogeneic hematopoietic stem cell transplant (HSCT).

Read the detailed description

Participants with a blood disease or cancer that can affect their infection-fighting white blood cells and those who have undergone a hematopoietic stem cell transplant (HSCT) and are receiving immunosuppressive therapy and have or are at risk of graft-vs-host disease (GVHD) are eligible for the study. These blood diseases and their treatments can weaken the immune system and may put individuals at high risk for a serious fungal infection of their internal organs or blood (invasive fungal infection). As these infections can be hard to detect early and can be life-threatening, many physicians believe that individuals diagnosed with these diseases should receive antifungal therapy to try to lower their risk of getting this type of infection.

Enrollment into this study will take place in several stages (parts). The determination of which part a participant will be in is based on which part is open at the site at the time of enrollment.

Conditions: Fungal Infections
Being tested: Posaconazole 200 mg, Posaconazole 300 mg
Medical subject headings: Mycoses

What participants receive

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

Posaconazole 200 mgDrug
Also called SCH 056592, MK-5592, Noxafil®
Posaconazole 300 mgDrug
Also called SCH 056592, MK-5592, Noxafil®

Study groups in NCT01777763
Study group	Role	What they receive
Posaconazole 200 mg	Experimental	Posaconazole 200 mg (two 100 mg tablets) twice daily (BID) on Day 1 followed by 200 mg (two 100 mg tablets) once daily (QD) for up to 28 days Receives: Drug: Posaconazole 200 mg
Posaconazole 300 mg	Experimental	Posaconazole 300 mg (three 100 mg tablets) BID on Day 1 followed by 300 mg (three 100 mg tablets) QD for up to 28 days Receives: Drug: Posaconazole 300 mg

What is being measured

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

Average Concentration (Cavg) of Posaconazole Tablet
Posaconazole steady-state concentrations of posaconazole in the plasma reached after regular and repeated dosing were used to estimate pharmacokinetic (PK) parameters for each participant where Cavg was defined as area under the plasma concentration versus time curve divided by the dosing interval.
Blood samples for the assessment of Cavg were collected on Day 1 and Day 8 predose and then at specified time points up to 24 hours postdose.
Measured: Predose on Day 1 up to 24 hours postdose on Day 8
Minimum Concentration (Cmin) of Posaconazole Tablet
Cmin was defined as posaconazole trough level immediately before a participant received the dose of posaconazole tablets on the specified day. Trough (Cmin) level blood samples for determination of posaconazole in plasma were collected for all participants on Day 1, Day 2, Day 3, and Day 8. On Day 1, the trough level sample was collected the before the first dose of study drug. On Day 2, trough samples were collected approximately 12 hours after the second dose of study drug was administered on Day 1. On all subsequent days, trough samples were collected approximately 24 hours following the previous day's dose of study drug.
Measured: Predose on Day 1 up to 24 hours postdose on Day 8
Maximum Concentration (Cmax) of Posaconazole Tablet
Blood samples for the assessment of Cmax were collected on Day 1 and Day 8 predose and then at specified time points up to 24 hours postdose.
Measured: Predose on Day 1 up to 24 hours postdose on Day 8
Time to Maximum Concentration (Tmax) of Posaconazole Tablet
Blood samples for the assessment of Tmax were collected on Day 1 and Day 8 predose and then at specified time points up to 24 hours postdose.
Measured: Predose on Day 1 up to 24 hours postdose on Day 8
Apparent Total Body Clearance (CL/F) for Posaconazole Tablet
Blood samples for the assessment of CL/F, the rate at which posaconazole was removed from the body, were collected on Day 1 and Day 8 predose and then at specified time points up to 24 hours postdose.
Measured: Predose on Day 1 up to 24 hours postdose on Day 8

Timeline

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

Jun 2009Feb 2012

First posted29 Jan 2013 (estimated)
Study startJun 2009
Primary completionFeb 2012
Study completionFeb 2012

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (3)Papers the sponsor has linked to this study.
Other trials for Fungal InfectionsStudies of the same condition, open and under way.
More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
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 1
Primary purpose: Prevention
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Enrolment: 230 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01777763
Sponsor's protocol ID: P05615
Other IDs: 2008-006684-36, 5592-065, 2008
Status last verified: Mar 2017
First submitted: 25 Jan 2013
Last updated: 7 Apr 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: Yes: http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final\_Updated%20July\_9\_2014.pdf http://engagezone.msd.com/ds\_documentation.php

Publications

Duarte RF, Lopez-Jimenez J, Cornely OA, Laverdiere M, Helfgott D, Haider S, Chandrasekar P, Langston A, Perfect J, Ma L, van Iersel ML, Connelly N, Kartsonis N, Waskin H. Phase 1b study of new posaconazole tablet for prevention of invasive fungal infections in high-risk patients with neutropenia. Antimicrob Agents Chemother. 2014 Oct;58(10):5758-65. doi: 10.1128/AAC.03050-14. Epub 2014 Jul 21.
PubMed 25049247
Cornely OA, Duarte RF, Haider S, Chandrasekar P, Helfgott D, Jimenez JL, Candoni A, Raad I, Laverdiere M, Langston A, Kartsonis N, Van Iersel M, Connelly N, Waskin H. Phase 3 pharmacokinetics and safety study of a posaconazole tablet formulation in patients at risk for invasive fungal disease. J Antimicrob Chemother. 2016 Mar;71(3):718-26. doi: 10.1093/jac/dkv380. Epub 2015 Nov 26.
PubMed 26612870
de Almeida C, Wong M, Kleijn HJ, Wrishko RE. Predicted Bezlotoxumab Exposure in Patients Who Have Received a Hematopoietic Stem Cell Transplant. Clin Ther. 2023 Apr;45(4):356-362. doi: 10.1016/j.clinthera.2023.02.006. Epub 2023 Mar 9.
PubMed 36906440

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?

Official record

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All Fungal Infections trials

Study at a glance

From the registry record, last updated by the sponsor on 7 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Pharmacokinetics and Safety of Solid Oral Posaconazole (SCH 56592) in Subjects at High Risk for Invasive Fungal Infections (Phase 1b; Protocol No. P05615)
ClinicalTrials.gov ID: NCT01777763
Acronym / sponsor ID: P05615
Conditions: Fungal Infections
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 230 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: Jun 2009
Primary completion: Feb 2012 (actual)
Study completion: Feb 2012 (actual)
First posted: 29 Jan 2013 (estimated)
Results: Posted 28 Mar 2013

Clinical summary

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

Detailed description

Enrollment into this study will take place in several stages (parts). The determination of which part a participant will be in is based on which part is open at the site at the time of enrollment.

Study design

Primary purpose: Prevention
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Posaconazole 200 mg	Experimental	Drug: Posaconazole 200 mgPosaconazole 200 mg (two 100 mg tablets) twice daily (BID) on Day 1 followed by 200 mg (two 100 mg tablets) once daily (QD) for up to 28 days
Posaconazole 300 mg	Experimental	Drug: Posaconazole 300 mgPosaconazole 300 mg (three 100 mg tablets) BID on Day 1 followed by 300 mg (three 100 mg tablets) QD for up to 28 days

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

Body weight >34 kg (75 lb) and of any race/ethnicity
Able to swallow oral tablets whole
Anticipated (likely to develop within 3-5 days) or documented neutropenia due to chemotherapy, chemotherapy for a new diagnosis of acute myelogenous leukemia (AML), or AML in first relapse; myelodysplastic syndromes (MDS) in transformation to AML; allogeneic hematopoietic stem cell transplant (HSCT) participants in the pre-engraftment period or in the post-engraftment period if they are receiving immunosuppressive therapy for graft versus host disease

Key exclusion criteria (10 listed)

Female must not be pregnant, must not intend to become pregnant
during the study, and must not be nursing
History of hypersensitivity to azoles
Moderate or severe liver dysfunction defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels greater than three times the upper limit of normal (ULN), AND a total bilirubin level greater than two times the ULN
Electrocardiogram (ECG) with corrected QTc interval greater than 500 msec

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 200 mgAlso: SCH 056592, MK-5592, Noxafil®	Drug	Posaconazole 200 mg
Posaconazole 300 mgAlso: SCH 056592, MK-5592, Noxafil®	Drug	Posaconazole 300 mg

Primary outcome

Average Concentration (Cavg) of Posaconazole Tablet
Time frame: Predose on Day 1 up to 24 hours postdose on Day 8
Posaconazole steady-state concentrations of posaconazole in the plasma reached after regular and repeated dosing were used to estimate pharmacokinetic (PK) parameters for each participant where Cavg was defined as area under the plasma concentration versus time curve divided by the dosing interval. Blood samples for the assessment of Cavg were collected on Day 1 and Day 8 predose and then at specified time points up to 24 hours postdose.
Minimum Concentration (Cmin) of Posaconazole Tablet
Time frame: Predose on Day 1 up to 24 hours postdose on Day 8
Cmin was defined as posaconazole trough level immediately before a participant received the dose of posaconazole tablets on the specified day. Trough (Cmin) level blood samples for determination of posaconazole in plasma were collected for all participants on Day 1, Day 2, Day 3, and Day 8. On Day 1, the trough level sample was collected the before the first dose of study drug. On Day 2, trough samples were collected approximately 12 hours after the second dose of study drug was administered on Day 1. On all subsequent days, trough samples were collected approximately 24 hours following the previous day's dose of study drug.
Maximum Concentration (Cmax) of Posaconazole Tablet
Time frame: Predose on Day 1 up to 24 hours postdose on Day 8
Blood samples for the assessment of Cmax were collected on Day 1 and Day 8 predose and then at specified time points up to 24 hours postdose.
Time to Maximum Concentration (Tmax) of Posaconazole Tablet
Time frame: Predose on Day 1 up to 24 hours postdose on Day 8
Blood samples for the assessment of Tmax were collected on Day 1 and Day 8 predose and then at specified time points up to 24 hours postdose.
Apparent Total Body Clearance (CL/F) for Posaconazole Tablet
Time frame: Predose on Day 1 up to 24 hours postdose on Day 8
Blood samples for the assessment of CL/F, the rate at which posaconazole was removed from the body, were collected on Day 1 and Day 8 predose and then at specified time points up to 24 hours postdose.

Results and safety

Results posted to the registry on 28 Mar 2013, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Posaconazole 200 mg	20	16
Posaconazole 300 mg	210	163

Primary outcome: Average Concentration (Cavg) of Posaconazole Tablet

Time frame: Predose on Day 1 up to 24 hours postdose on Day 8. Mean (Standard Deviation). Unit: ng/mL

Measure	Posaconazole 200 mg n = 18	Posaconazole 300 mg n = 50
Value	981 (475)	1580 (667)

Population analysed: The Cavg PK population included participants who met the inclusion/exclusion criteria, complied with protocol procedures including collection of specified PK and dosing parameters, had no major protocol violations, and had documented adherence to dosing and PK regimens through the Day 8 steady-state visit.

Primary outcome: Minimum Concentration (Cmin) of Posaconazole Tablet

Time frame: Predose on Day 1 up to 24 hours postdose on Day 8. Mean (Standard Deviation). Unit: ng/mL

Measure	Posaconazole 200 mg n = 18	Posaconazole 300 mg n = 50
Value	812 (443)	1310 (647)

Population analysed: The Cmin PK population included participants who met the inclusion/exclusion criteria, complied with protocol procedures including collection of specified PK and dosing parameters, had no major protocol violations, and had documented adherence to dosing and PK regimens through the Day 8 steady-state visit.

Primary outcome: Maximum Concentration (Cmax) of Posaconazole Tablet

Time frame: Predose on Day 1 up to 24 hours postdose on Day 8. Mean (Standard Deviation). Unit: ng/mL

Measure	Posaconazole 200 mg n = 18	Posaconazole 300 mg n = 50
Day 1	652 (217)	908 (354)
Day 8	1310 (617)	2090 (798)

Population analysed: The Cmax PK population included participants who met the inclusion/exclusion criteria, complied with protocol procedures including collection of specified PK and dosing parameters, had no major protocol violations, and had documented adherence to dosing and PK regimens through the Day 8 steady-state visit.

Primary outcome: Time to Maximum Concentration (Tmax) of Posaconazole Tablet

Time frame: Predose on Day 1 up to 24 hours postdose on Day 8. Median (Full Range). Unit: Hours

Measure	Posaconazole 200 mg n = 18	Posaconazole 300 mg n = 50
Day 1	4 (1.9 to 4.1)	4 (1.8 to 12.0)
Day 8	4 (2.0 to 8.1)	4 (1.3 to 8.3)

Population analysed: The Tmax PK population included participants who met the inclusion/exclusion criteria, complied with protocol procedures including collection of specified PK and dosing parameters, had no major protocol violations, and had documented adherence to dosing and PK regimens through the Day 8 steady-state visit.

Adverse events

Time frame: Up to Day 65. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Posaconazole 200 mg	6 of 20 (30%)	20 of 20 (100%)	Not reported
Posaconazole 300 mg	69 of 210 (32.9%)	186 of 210 (88.6%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 7 Apr 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 25049247Duarte RF, Lopez-Jimenez J, Cornely OA, Laverdiere M, Helfgott D, Haider S, Chandrasekar P, Langston A, Perfect J, Ma L, van Iersel ML, Connelly N, Kartsonis N, Waskin H. Phase 1b study of new posaconazole tablet for prevention of invasive fungal infections in high-risk patients with neutropenia. Antimicrob Agents Chemother. 2014 Oct;58(10):5758-65. doi: 10.1128/AAC.03050-14. Epub 2014 Jul 21.
Results publication: PubMed 26612870Cornely OA, Duarte RF, Haider S, Chandrasekar P, Helfgott D, Jimenez JL, Candoni A, Raad I, Laverdiere M, Langston A, Kartsonis N, Van Iersel M, Connelly N, Waskin H. Phase 3 pharmacokinetics and safety study of a posaconazole tablet formulation in patients at risk for invasive fungal disease. J Antimicrob Chemother. 2016 Mar;71(3):718-26. doi: 10.1093/jac/dkv380. Epub 2015 Nov 26.
Derived from this study: PubMed 36906440de Almeida C, Wong M, Kleijn HJ, Wrishko RE. Predicted Bezlotoxumab Exposure in Patients Who Have Received a Hematopoietic Stem Cell Transplant. Clin Ther. 2023 Apr;45(4):356-362. doi: 10.1016/j.clinthera.2023.02.006. Epub 2023 Mar 9.
Individual participant dataSharing planned: Yes. http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf http://engagezone.msd.com/ds_documentation.php

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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.

The record lists no contact. Use the official record to reach the sponsor.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Posaconazole 200 mg and Posaconazole 300 mg in people with Fungal Infections, run by Merck Sharp & Dohme LLC.

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 3 inclusion and 10 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 7 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.

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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Mar 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Average Concentration (Cavg) of Posaconazole Tablet (time frame: Predose on Day 1 up to 24 hours postdose on Day 8). The study lists 5 primary outcomes in all. 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 NCT01777763, which also lists 3 linked publications.

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 7 Apr 2017.