Fungal InfectionPhase 1NCT02387983

Pharmacokinetics and Safety of Oral Posaconazole (MK-5592)Tablets in Chinese Participants at High Risk for Invasive Fungal Infections (MK-5592-117)

A Phase 1 study testing Posaconazole in people with Fungal Infection, run by Merck Sharp & Dohme LLC.

Completed

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

Trial summary

The purpose of this study is to evaluate the pharmacokinetics and safety of oral posaconazole tablets in Chinese participants at high risk for invasive fungal infections. Neutropenic participants undergoing chemotherapy for acute myelogenous leukemia or myelodysplastic syndromes will be enrolled in the study. Read more about this study

Who is it for?: Ages 18 to 70 years
Conditions the study is for: Fungal Infection
What is being tested?: Posaconazole
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 65 participants
Where: No sites listed yet
Study dates: 6 May 2015to 2 May 2016
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 to 70 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Chinese participant
Female of reproductive potential with a serum hCG level consistent with a nongravid state and agree to use 2 acceptable methods of birth control throughout the study
Body Mass Index (BMI) >=15 and <=30 kg/m^2
Anticipated or documented prolonged neutropenia and likely to last for at least 7 days due to: a) standard intensive chemotherapy, anthracycline-based or other accepted regimen (excluding any investigational agent) for a new diagnosis of acute myelogenous leukemia (AML); b)chemotherapy for AML in first relapse; or c) therapy for myelodysplastic syndromes in transformation to AML or other diagnoses of secondary AML (therapy related, antecedent hematological disorders) or chronic myelogenous leukemia in blast crisis
Free from any clinically significant disease other than the primary hematologic disease that would interfere with administration of study medication or study evaluations

Who cannot join

Pregnant, intends to become pregnant during the study, or has been nursing
Mentally or legally incapacitated, has significant emotional problems, or has clinically significant psychiatric disorder over the last 5 years
Received systemic antifungal therapy (oral, intravenous, or inhaled) within 30 days of study enrollment for reasons other than antifungal prophylaxis
Known or suspected invasive or systemic fungal infection
Taken posaconazole within 10 days prior to study enrollment
Major surgery, donated or lost 1 unit of blood, or participated in another investigational study within 4 weeks prior to the study

Show all 14Show fewer

Type 1 hypersensitivity or idiosyncratic reactions to azole agents
Significant multiple or severe allergies, or has had an anaphylactic reaction or significant intolerability to drugs or food
Moderate or severe liver dysfunction
Chronic active hepatitis, cirrhosis, Hepatocellular Carcinoma (HCC), or other hepatic disease caused by a virus
Previous electrocardiogram with a prolonged QTc interval
Prior enrollment in this study or other posaconazole studies within 90 days of study entry
Eastern Cooperative Oncology Group (ECOG) performance status was >2 prior to induction chemotherapy for the underlying disease
Known or suspected Gilbert's disease

About this study

Official title: Pharmacokinetics and Safety of Solid Oral Posaconazole (MK-5592, POS) in Chinese Subjects at High Risk for Invasive Fungal Infections

Conditions: Fungal Infection
Being tested: Posaconazole
Medical subject headings: Mycoses

What participants receive

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

PosaconazoleDrug
Also called MK-5592
Posaconazole 300 mg solid oral tablet

Study groups in NCT02387983
Study group	Role	What they receive
Posaconazole	Experimental	Posaconazole 300 mg tablet (3 x 100 mg tablets) once every 12 hours on Day 1 and once-daily on Days 2 to 28 Receives: Drug: Posaconazole

What is being measured

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

Steady-state Average Concentration (ssCavg) of Posaconazole on Day 8
The ssCavg was calculated in order to determine the percentage of participants achieving the pharmacokinetic (PK) target of ssCavg >500 ng/mL on Day 8 when plasma drug levels had reached steady state.
Measured: Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose on Day 8
Steady-state Area Under the Concentration-time Curve (ssAUC0-24hr) of Posaconazole on Day 8
The ssAUC0-24hr was calculated to determine the mean plasma drug concentration in the Intensive and Sparse PK subgroup from immediately after dosing to 24 hours post-dose on Day 8. Results data are presented as the arithmetic mean (% arithmetic coefficient of variation [CV]), where CV is calculated as (100 x standard deviation/arithmetic mean).
Measured: Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose on Day 8
Steady-state Maximum Concentration (ssCmax) of Posaconazole on Day 8
The ssCmax was calculated in order to determine the maximum post-dose plasma drug concentration in the Intensive and Sparse PK subgroup on Day 8. Results data are presented as the arithmetic mean (% arithmetic coefficient of variation [CV]), where CV is calculated as (100 x standard deviation/arithmetic mean).
Measured: Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose on Day 8
Steady-state Minimum Concentration (ssCmin) of Posaconazole on Day 8
The ssCmin was calculated in order to determine the lowest measurable drug concentration in the Intensive and Sparse PK subgroup up to 24 hours post-dose on Day 8. Results data are presented as the arithmetic mean (% arithmetic coefficient of variation [CV]), where CV is calculated as (100 x standard deviation/arithmetic mean).
Measured: Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose on Day 8
Time to Steady-state Maximum Concentration (ssTmax) of Posaconazole on Day 8
The ssTmax was calculated in order to determine the amount of time required to reach ssCmax in the Intensive and Sparse PK subgroup on Day 8.
Measured: Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose on Day 8
AUC0-24hr of Posaconazole on Day 1
The AUC0-24hr was calculated to determine the mean plasma drug concentration from immediately after dosing to 24 hours post-dose in the Immediate and Sparse PK subgroup on Day 1. Results data are presented as the arithmetic mean (% arithmetic coefficient of variation [CV]), where CV is calculated as (100 x standard deviation/arithmetic mean).
Measured: Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose on Day 1
Cmax of Posaconazole on Day 1
The Cmax was calculated to determine the maximum plasma drug concentration up to 24 hours post-dose in the Immediate and Sparse PK subgroup on Day 1. Results data are presented as the arithmetic mean (% arithmetic coefficient of variation [CV]), where CV is calculated as (100 x standard deviation/arithmetic mean).
Measured: Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose on Day 1
Cmin of Posaconazole on Day 1
The Cmin was calculated in order to determine the lowest measurable drug concentration from immediately after dosing to 24 hours post-dose in the Immediate and Sparse PK subgroup on Day 1. Results data are presented as the arithmetic mean (% arithmetic coefficient of variation [CV]), where CV is calculated as (100 x standard deviation/arithmetic mean).
Measured: Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose on Day 1
Tmax of Posaconazole on Day 1
The Tmax was calculated in order to determine the time required to reach Cmax in the Immediate and Sparse PK subgroup on Day 1.
Measured: Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose on Day 1

Timeline

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

6 May 20152 May 2016

First posted13 Mar 2015 (estimated)
Study start6 May 2015
Primary completion2 May 2016
Study completion2 May 2016

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 (1)Papers the sponsor has linked to this study.
Other trials for Fungal InfectionStudies 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: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 65 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02387983
Sponsor's protocol ID: 5592-117
Status last verified: Sep 2018
First submitted: 9 Mar 2015
Last updated: 9 Oct 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: Yes: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Publications

Liu K, Wu D, Li J, Chen H, Ning H, Zhao T, Dai H, Chen L, Mangin E, Winchell GA, Waskin H, Jiang J, Qiu Y, Zhao XM. Pharmacokinetics and Safety of Posaconazole Tablet Formulation in Chinese Participants at High Risk for Invasive Fungal Infection. Adv Ther. 2020 May;37(5):2493-2506. doi: 10.1007/s12325-020-01341-x. Epub 2020 Apr 22.
PubMed 32319040

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 Infection trials

Study at a glance

From the registry record, last updated by the sponsor on 9 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Pharmacokinetics and Safety of Solid Oral Posaconazole (MK-5592, POS) in Chinese Subjects at High Risk for Invasive Fungal Infections
ClinicalTrials.gov ID: NCT02387983
Acronym / sponsor ID: 5592-117
Conditions: Fungal Infection
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 65 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: 6 May 2015 (actual)
Primary completion: 2 May 2016 (actual)
Study completion: 2 May 2016 (actual)
First posted: 13 Mar 2015 (estimated)
Results: Posted 14 Jul 2017

Clinical summary

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

Study design

Primary purpose: Prevention
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Posaconazole	Experimental	Drug: PosaconazolePosaconazole 300 mg tablet (3 x 100 mg tablets) once every 12 hours on Day 1 and once-daily on Days 2 to 28

Who may qualify

Ages: 18 to 70 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

Chinese participant
Female of reproductive potential with a serum hCG level consistent with a nongravid state and agree to use 2 acceptable methods of birth control throughout the study
Body Mass Index (BMI) >=15 and <=30 kg/m^2
Anticipated or documented prolonged neutropenia and likely to last for at least 7 days due to: a) standard intensive chemotherapy, anthracycline-based or other accepted regimen (excluding any investigational agent) for a new diagnosis of acute myelogenous leukemia (AML); b)chemotherapy for AML in first relapse; or c) therapy for myelodysplastic syndromes in transformation to AML or other diagnoses of secondary AML (therapy related, antecedent hematological disorders) or chronic myelogenous leukemia in blast crisis
Free from any clinically significant disease other than the primary hematologic disease that would interfere with administration of study medication or study evaluations

Key exclusion criteria (14 listed)

Pregnant, intends to become pregnant during the study, or has been nursing
Mentally or legally incapacitated, has significant emotional problems, or has clinically significant psychiatric disorder over the last 5 years
Received systemic antifungal therapy (oral, intravenous, or inhaled) within 30 days of study enrollment for reasons other than antifungal prophylaxis
Known or suspected invasive or systemic fungal infection
Taken posaconazole within 10 days prior to study enrollment

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
PosaconazoleAlso: MK-5592Posaconazole 300 mg solid oral tablet	Drug	Posaconazole

Primary outcome

Steady-state Average Concentration (ssCavg) of Posaconazole on Day 8
Time frame: Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose on Day 8
The ssCavg was calculated in order to determine the percentage of participants achieving the pharmacokinetic (PK) target of ssCavg >500 ng/mL on Day 8 when plasma drug levels had reached steady state.
Steady-state Area Under the Concentration-time Curve (ssAUC0-24hr) of Posaconazole on Day 8
Time frame: Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose on Day 8
The ssAUC0-24hr was calculated to determine the mean plasma drug concentration in the Intensive and Sparse PK subgroup from immediately after dosing to 24 hours post-dose on Day 8. Results data are presented as the arithmetic mean (% arithmetic coefficient of variation [CV]), where CV is calculated as (100 x standard deviation/arithmetic mean).
Steady-state Maximum Concentration (ssCmax) of Posaconazole on Day 8
Time frame: Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose on Day 8
The ssCmax was calculated in order to determine the maximum post-dose plasma drug concentration in the Intensive and Sparse PK subgroup on Day 8. Results data are presented as the arithmetic mean (% arithmetic coefficient of variation [CV]), where CV is calculated as (100 x standard deviation/arithmetic mean).
Steady-state Minimum Concentration (ssCmin) of Posaconazole on Day 8
Time frame: Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose on Day 8
The ssCmin was calculated in order to determine the lowest measurable drug concentration in the Intensive and Sparse PK subgroup up to 24 hours post-dose on Day 8. Results data are presented as the arithmetic mean (% arithmetic coefficient of variation [CV]), where CV is calculated as (100 x standard deviation/arithmetic mean).
Time to Steady-state Maximum Concentration (ssTmax) of Posaconazole on Day 8
Time frame: Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose on Day 8
The ssTmax was calculated in order to determine the amount of time required to reach ssCmax in the Intensive and Sparse PK subgroup on Day 8.
AUC0-24hr of Posaconazole on Day 1
Time frame: Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose on Day 1
The AUC0-24hr was calculated to determine the mean plasma drug concentration from immediately after dosing to 24 hours post-dose in the Immediate and Sparse PK subgroup on Day 1. Results data are presented as the arithmetic mean (% arithmetic coefficient of variation [CV]), where CV is calculated as (100 x standard deviation/arithmetic mean).
Cmax of Posaconazole on Day 1
Time frame: Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose on Day 1
The Cmax was calculated to determine the maximum plasma drug concentration up to 24 hours post-dose in the Immediate and Sparse PK subgroup on Day 1. Results data are presented as the arithmetic mean (% arithmetic coefficient of variation [CV]), where CV is calculated as (100 x standard deviation/arithmetic mean).
Cmin of Posaconazole on Day 1
Time frame: Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose on Day 1
The Cmin was calculated in order to determine the lowest measurable drug concentration from immediately after dosing to 24 hours post-dose in the Immediate and Sparse PK subgroup on Day 1. Results data are presented as the arithmetic mean (% arithmetic coefficient of variation [CV]), where CV is calculated as (100 x standard deviation/arithmetic mean).
Tmax of Posaconazole on Day 1
Time frame: Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose on Day 1
The Tmax was calculated in order to determine the time required to reach Cmax in the Immediate and Sparse PK subgroup on Day 1.

Results and safety

Results posted to the registry on 14 Jul 2017, 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	65	58

Primary outcome: Steady-state Average Concentration (ssCavg) of Posaconazole on Day 8

Time frame: Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose on Day 8. Number. Unit: Percentage of Participants

Measure	Posaconazole n = 44
ssCavg < 500 ng/mL	0.0
500 ng/mL ≤ ssCavg < 2500 ng/mL	88.9
2500 ng/mL ≤ ssCavg < 3750 ng/mL	11.1
ssCavg ≥ 3750 ng/mL	0

Population analysed: The PK analysis set included all randomized and treated participants who complied with the protocol and have documented adherence to daily dosing and PK regimens through the Day 8 steady-state evaluation and have data available.

Primary outcome: Steady-state Area Under the Concentration-time Curve (ssAUC0-24hr) of Posaconazole on Day 8

Time frame: Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose on Day 8. Mean (Standard Deviation). Unit: hr*ng/mL

Measure	Posaconazole n = 18
Value	38600 (42.8)

Population analysed: The PK analysis set included all randomized and treated participants in the Intensive and Sparse PK subgroup who complied with the protocol and have documented adherence to daily dosing and PK regimens through the Day 8 steady-state evaluation and have data available.

Primary outcome: Steady-state Maximum Concentration (ssCmax) of Posaconazole on Day 8

Time frame: Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose on Day 8. Mean (Standard Deviation). Unit: ng/mL

Measure	Posaconazole n = 18
Value	2150 (43.9)

Primary outcome: Steady-state Minimum Concentration (ssCmin) of Posaconazole on Day 8

Time frame: Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose on Day 8. Mean (Standard Deviation). Unit: ng/mL

Measure	Posaconazole n = 18
Value	1310 (43.6)

Population analysed: The PK analysis set included all randomized and treated participants in the Intensive and Sparse subgroup who complied with the protocol and have documented adherence to daily dosing and PK regimens through the Day 8 steady-state evaluation with available data.

Adverse events

Time frame: Up to Day 42. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
MK-5592	4 of 65 (6.2%)	64 of 65 (98.5%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 9 Oct 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 32319040Liu K, Wu D, Li J, Chen H, Ning H, Zhao T, Dai H, Chen L, Mangin E, Winchell GA, Waskin H, Jiang J, Qiu Y, Zhao XM. Pharmacokinetics and Safety of Posaconazole Tablet Formulation in Chinese Participants at High Risk for Invasive Fungal Infection. Adv Ther. 2020 May;37(5):2493-2506. doi: 10.1007/s12325-020-01341-x. Epub 2020 Apr 22.
Individual participant dataSharing planned: Yes. https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Related trials for Fungal Infection

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RecruitingObservational study
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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.

Medical Director study director

Merck Sharp & Dohme LLC

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Posaconazole in people with Fungal Infection, 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 5 inclusion and 14 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 9 Oct 2018. 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 14 Jul 2017). 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?

Steady-state Average Concentration (ssCavg) of Posaconazole on Day 8 (time frame: Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose on Day 8). The study lists 9 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 NCT02387983, 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 9 Oct 2018.