Modified Release Posaconazole in Patients With Cystic Fibrosis

A prospective single center observational cohort of patients with cystic fibrosis to determine whether adequate serum levels of posaconazole, after administration of the newer modified release once daily oral formulation, can be achieved.

Study Overview

• Status: Unknown
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: Posaconazole

Detailed Description

Use of antifungals has increased in people with cystic fibrosis. Aspergillus is the dominant fungal pathogen in this patient population and thus far, voriconazole has been used first line. Apart from recurrent and chronic lung infections, people with cystic fibrosis can also have problems with their gastrointestinal tract and absorption, and can develop chronic liver disease. As a consequence, they are at high-risk for not achieving adequate antifungal levels, which may be due to altered oral bioavailability, and they may be more susceptible to hepatic toxicities.

This study will evaluate the use of the newer modified release, once daily formulation of posaconazole in people with cystic fibrosis to identify if there is any difference in the bioavailability of the drug due to the effect of cystic fibrosis on the gastrointestinal tract. This newer formulation of once daily posaconazole is approved by the Therapeutic Goods Administration (TGA) and available on the Pharmaceutical Benefits Scheme (PBS) since March 2015. The newer formulation has the potential to overcome one of the major challenges with antifungals in cystic fibrosis; oral bioavailability. Posaconazole also appears to have reduced hepatotoxicity. This study will focus on the safety and tolerability of the drug, as well as pharmacological and microbiological endpoints.

20 eligible participants will be enrolled and have a

• Pre-treatment sputum will be collected as standard of care.
• Posaconazole serum levels will be taken at days 2, 5 and 7. (Day 5 and 7 as standard of care).
• renal and liver function assessed whilst on treatment as standard of care.
• followed up for 30 days to assess tolerability and monitor for the development of liver toxicity

• Study Type: Observational
• Enrollment (Anticipated): 20

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Recruiting
      • Alfred Hospital
      • Contact: Janine Roney; Phone Number: +61390762296; Email: j.roney@alfred.org.au
      • Principal Investigator: A Peleg, Prof

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Patients with cystic fibrosis attending care at the Alfred Hospital in Melbourne Australia

Description

• Albe to provide written informed consent
• Greater than 18 years of age or older
• Have a diagnosis of cystic fibrosis
• To commence as part of their standard of care the newer modified release oral formulation of posaconazole to treat Aspergillus
• Able to provide a pre-treatment sputum collected for fungal culture as part of standard of care
• Have been prescribed a loading dose of 300mg bd for 1 day of the modified release posaconazole tablet followed by 300mg daily.

Exclusion Criteria:

• • Known azole hypersensitivity

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Cystic Fibrosis on Posaconazole; Able to provide written informed consent; Greater than 18 years of age or older; Have a diagnosis of cystic fibrosis; No known azole hypersensitivity; To commence as part of their standard of care the newer modified release oral formulation of posaconazole to treat Aspergillus; Able to provide a pre-treatment sputum collected for fungal culture as part of standard of care; Have been prescribed a loading dose of 300mg bd for 1 day of the modified release posaconazole tablet followed by 300mg daily.

Drug: Posaconazole; A triazole antifungal drug that is used to treat invasive infections by Candida species and Aspergillus species in severely immunocompromised patients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum levels of posaconazole in patients with cystic fibrosis taking the newer modified release once daily oral formulation.	Posaconazole serum levels at days 2, 5 and 7	7 days

Collaborators and Investigators

• Sponsor: Bayside Health

Publications and helpful links

Helpful Links

• Rey E, Treluyer J, Pons G. Drug Dispostion in Cysytic Fibrosis. Clin Pharmacokinet 1998 Oct; 35 (4): 313-329
• Green MR, Wollery JE. Posaconazole Serum Level on Day 2 Predicts Steady State Posaconazole Serum level. Ther Drug Monit • Volume 34, Number 1, February 2012
• Zhang H, Nguyen M, Clancy J et al. Pharmacokinetics of Posaconazole Suspension in Lung Transplant Patients with and without Cystic Fibrosis. Antimicrob Agents Chemother. 2016 Jun; 60(6): 3558-3562

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2018
• Primary Completion (Anticipated): February 5, 2021
• Study Completion (Anticipated): February 5, 2021

Study Registration Dates

• First Submitted: December 27, 2017
• First Submitted That Met QC Criteria: January 29, 2018
• First Posted (Actual): February 5, 2018

Study Record Updates

• Last Update Posted (Actual): October 26, 2020
• Last Update Submitted That Met QC Criteria: October 22, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: posaconazole
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis; 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: 432.17

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes