Fungal InfectionPhase 4PAPALNCT01667107

A Pharmacokinetic Analysis of Posaconazole in Lung Transplant Recipients (MK-5592-105)

A Phase 4 study testing Posaconazole and Calogen® in people with Fungal Infection, run by Merck Sharp & Dohme LLC.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Trial summary

This single site study will examine plasma and alveolar compartment (AC) levels of posaconazole in cystic fibrosis (CF) and non-cystic fibrosis (non-CF) lung transplant recipients receiving routine post-operative anti-fungal prophylaxis. Invasive fungal infection rates will be assessed following transplantation. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Fungal Infection
What is being tested?: Posaconazole and Calogen®
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 26 participants
Where: No sites listed yet
Study dates: 23 Jan 2013to 16 Jan 2014
Phase: Phase 4
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

Scheduled to undergo lung transplantation
Able to take oral/nasogastric medication
Females of childbearing potential, males, and the sexual partners of males must use an effective method of birth control during this study and for 6 weeks after completing the study.

Who cannot join

Severe liver disease
Current use of cytochrome P-450 (CYP)-3A4 inhibitors including terfenadine, astemizole, cisapride, pimozide, halofantrine or quinidine within 7 days before transplant
Treatment with posaconazole within 14 days before transplant
Breastfeeding

About this study

Official title: A Pharmacokinetic Analysis of Posaconazole in the Plasma and Alveolar Compartment of Lung Transplant Recipients

Conditions: Fungal Infection
Being tested: Posaconazole, Calogen®
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 SCH056592, MK-5592, Noxafil®
Calogen®Drug

Study groups in NCT01667107
Study group	Role	What they receive
Posaconazole - CF Participants	Experimental	Posaconazole 400 mg oral solution twice daily administered with Calogen® to optimize absorption for a total of 6 weeks starting within 12 hours of leaving surgery, thereafter administered in the hospital or as an outpatient; the dose could be changed to posaconazole 200 mg 4 times per day if the participant is unable to meet the conditions for optimal absorption of posaconazole. Receives: Drug: Posaconazole; Drug: Calogen®
Posaconazole - Non-CF Participants	Experimental	Posaconazole 400 mg oral solution twice daily administered with Calogen® to optimize absorption for a total of 6 weeks starting within 12 hours of leaving surgery, thereafter administered in the hospital or as an outpatient; the dose could be changed to posaconazole 200 mg 4 times per day if the participant is unable to meet the conditions for optimal absorption of posaconazole. Receives: Drug: Posaconazole; Drug: Calogen®

What is being measured

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

Time to Reach 90% of the Steady State Serum Concentration of Posaconazole
Blood samples for measurement of serum posaconazole were collected approximately 4 hours after the first daily dose on Days 1-12 and every Monday and Thursday on Days 13-43. The time to reach 90% of the steady state serum posaconazole concentration was to be estimated from fitting a linear model to the concentration data over time. The data did not permit estimation of the endpoint from the modeling proposed in the protocol.
Measured: Four hours after the first daily dose on Days 1-12 and every Monday and Thursday on Days 13-43
Concentration of Posaconazole in Bronchoalveolar Lavage (BAL) and Serum
Concurrent BAL and serum samples for measurement of posaconazole concentration were to be collected during any clinically-indicated bronchoscopy. A participant could have more than 1 bronchoscopy.
Measured: Up to Day 42

Secondary outcomes (1)

Percentage of Participants Who Develop Invasive Fungal Infection
Invasive fungal infection was assessed using the Mycoses Study Group/European Organisation for Research and Treatment of Cancer (MSG/EORTC) criteria. Infections counted in the analysis were those classified as 'proven', 'probable', or 'possible' according to the criteria.
Measured: Up to Day 84

Timeline

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

23 Jan 201316 Jan 2014

First posted17 Aug 2012 (estimated)
Study start23 Jan 2013
Primary completion16 Jan 2014
Study completion16 Jan 2014

Why it stopped: Study terminated due to an unfavorable risk-benefit analysis

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.
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 4
Primary purpose: Prevention
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 26 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01667107
Sponsor's protocol ID: 5592-105
Other IDs: 2012-003140-68
Acronym: PAPAL
Status last verified: Sep 2018
First submitted: 14 Aug 2012
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

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: A Pharmacokinetic Analysis of Posaconazole in the Plasma and Alveolar Compartment of Lung Transplant Recipients
ClinicalTrials.gov ID: NCT01667107
Acronym / sponsor ID: PAPAL / 5592-105
Conditions: Fungal Infection
Phase: Phase 4
Study type: Interventional
Recruitment status: TerminatedReason stopped: Study terminated due to an unfavorable risk-benefit analysis
Enrolment: 26 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: 23 Jan 2013 (actual)
Primary completion: 16 Jan 2014 (actual)
Study completion: 16 Jan 2014 (actual)
First posted: 17 Aug 2012 (estimated)
Results: Posted 5 Jan 2015

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: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Posaconazole - CF Participants	Experimental	Drug: Posaconazole, Drug: Calogen®Posaconazole 400 mg oral solution twice daily administered with Calogen® to optimize absorption for a total of 6 weeks starting within 12 hours of leaving surgery, thereafter administered in the hospital or as an outpatient; the dose could be changed to posaconazole 200 mg 4 times per day if the participant is unable to meet the conditions for optimal absorption of posaconazole.
Posaconazole - Non-CF Participants	Experimental	Drug: Posaconazole, Drug: Calogen®Posaconazole 400 mg oral solution twice daily administered with Calogen® to optimize absorption for a total of 6 weeks starting within 12 hours of leaving surgery, thereafter administered in the hospital or as an outpatient; the dose could be changed to posaconazole 200 mg 4 times per day if the participant is unable to meet the conditions for optimal absorption of posaconazole.

Who may qualify

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

Key inclusion criteria (3 listed)

Scheduled to undergo lung transplantation
Able to take oral/nasogastric medication
Females of childbearing potential, males, and the sexual partners of males must use an effective method of birth control during this study and for 6 weeks after completing the study.

Key exclusion criteria (4 listed)

Severe liver disease
Current use of cytochrome P-450 (CYP)-3A4 inhibitors including terfenadine, astemizole, cisapride, pimozide, halofantrine or quinidine within 7 days before transplant
Treatment with posaconazole within 14 days before transplant
Breastfeeding

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: SCH056592, MK-5592, Noxafil®	Drug	Posaconazole - CF Participants, Posaconazole - Non-CF Participants
Calogen®	Drug	Posaconazole - CF Participants, Posaconazole - Non-CF Participants

Primary outcome

Time to Reach 90% of the Steady State Serum Concentration of Posaconazole
Time frame: Four hours after the first daily dose on Days 1-12 and every Monday and Thursday on Days 13-43
Blood samples for measurement of serum posaconazole were collected approximately 4 hours after the first daily dose on Days 1-12 and every Monday and Thursday on Days 13-43. The time to reach 90% of the steady state serum posaconazole concentration was to be estimated from fitting a linear model to the concentration data over time. The data did not permit estimation of the endpoint from the modeling proposed in the protocol.
Concentration of Posaconazole in Bronchoalveolar Lavage (BAL) and Serum
Time frame: Up to Day 42
Concurrent BAL and serum samples for measurement of posaconazole concentration were to be collected during any clinically-indicated bronchoscopy. A participant could have more than 1 bronchoscopy.

1 secondary outcome

Percentage of Participants Who Develop Invasive Fungal Infection
Time frame: Up to Day 84

Results and safety

Results posted to the registry on 5 Jan 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Cystic Fibrosis Participants	8	4
Non-Cystic Fibrosis Participants	18	11

Primary outcome: Time to Reach 90% of the Steady State Serum Concentration of Posaconazole

Time frame: Four hours after the first daily dose on Days 1-12 and every Monday and Thursday on Days 13-43

Population analysed: The population to be analyzed included participants who complied with the protocol sufficiently to ensure that the results would exhibit the effects of treatment

Primary outcome: Concentration of Posaconazole in Bronchoalveolar Lavage (BAL) and Serum

Time frame: Up to Day 42. Mean (Standard Deviation). Unit: mg/L

Measure	Cystic Fibrosis Participants n = 5	Non-Cystic Fibrosis Participants n = 7
BAL	1.116 (1.1699)	0.764 (0.800)
Serum	0.829 (0.3742)	0.7488 (0.3131)

Cystic Fibrosis Participants: Spearman rank correlation coefficient: 0.53, p = 0.139, Spearman rank correlation
Non-Cystic Fibrosis Participants: Spearman rank correlation coefficient: 0.59, p = 0.057, Spearman rank correlation

Population analysed: The population analyzed included all enrolled participants who had BAL and serum samples collected at the time of bronchoscopy and analyzed for posaconazole concentration. A participant could have more than 1 pair of samples (BAL and serum) included in the analysis.

1 secondary outcome is reported in the full results.

Adverse events

Time frame: Up to Day 88. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Cystic Fibrosis Participants	6 of 8 (75%)	1 of 8 (12.5%)	Not reported
Non-Cystic Fibrosis Participants	10 of 18 (55.6%)	2 of 18 (11.1%)	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.
Individual participant dataSharing planned: Yes. https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

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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 4 study testing Posaconazole and Calogen® 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 3 inclusion and 4 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: stopped early, 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 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?

Yes. Results are posted in the registry (first posted 5 Jan 2015). 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?

Time to Reach 90% of the Steady State Serum Concentration of Posaconazole (time frame: Four hours after the first daily dose on Days 1-12 and every Monday and Thursday on Days 13-43). The study lists 2 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 NCT01667107.

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.