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

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

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.

Study Overview

• Status: Terminated
• Conditions: Fungal Infection
• Intervention / Treatment: Drug: Posaconazole; Drug: Calogen®

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Posaconazole - CF Participants; 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; Other Names: MK-5592; Noxafil®; SCH056592; Drug: Calogen®
Experimental: Posaconazole - Non-CF Participants; 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; Other Names: MK-5592; Noxafil®; SCH056592; Drug: Calogen®

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Actual): January 23, 2013
• Primary Completion (Actual): January 16, 2014
• Study Completion (Actual): January 16, 2014

Study Registration Dates

• First Submitted: August 14, 2012
• First Submitted That Met QC Criteria: August 14, 2012
• First Posted (Estimate): August 17, 2012

Study Record Updates

• Last Update Posted (Actual): October 9, 2018
• Last Update Submitted That Met QC Criteria: September 10, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections and Mycoses; Mycoses; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; 14-alpha Demethylase Inhibitors; Trypanocidal Agents; Posaconazole
• Other Study ID Numbers: 5592-105; 2012-003140-68 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Study Data/Documents

1. CSR Synopsis