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

Study Overview
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Brief Summary
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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.

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

Conditions
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Fungal Infection

Intervention / Treatment
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* Drug: Posaconazole
* Drug: Calogen®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Posaconazole - CF Participants<br>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. | Drug: Posaconazole<br> <br> * Other names: Noxafil®;Drug: Calogen®<br> <br> |
| Experimental: Posaconazole - Non-CF Participants<br>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. | Drug: Posaconazole<br> <br> * Other names: Noxafil®;Drug: Calogen®<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | Up to Day 42 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Up to Day 84 |