A Pharmacokinetic Analysis of Posaconazole in Lung Transplant Recipients (MK-5592-105)
- Registration Number
- NCT01667107
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 26
- 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.
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Posaconazole - CF Participants 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 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 - CF Participants Posaconazole 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 Posaconazole 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.
- Primary Outcome Measures
Name Time Method Time to Reach 90% of the Steady State Serum Concentration of Posaconazole 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 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.
- Secondary Outcome Measures
Name Time Method Percentage of Participants Who Develop Invasive Fungal Infection Up to Day 84 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.