Steady-State Comparative Bioavailability Study in Prophylaxis Patients of Lozanoc® 50 mg With Sporanox® 100 mg

Steady-State Comparative Bioavailability Study in Patients Requiring Anti-Fungal Prophylaxis Comparing Twice a Day Dosing of Lozanoc® (Mayne) Regardless of Food With Sporanox® (Janssen) Under Fed Conditions

The pharmacokinetics of Sporanox and Lozanoc has not been compared in patients requiring anti-fungal prophylaxis or therapy. The present study is designed to compare the pharmacokinetics of Sporanox and Lozanoc in patients requiring primary prophylaxis. The 3-week exposure to each formulation is designed to allow for all participants to reach steady-state for each drug, as the time to steady-state can vary.

Study Overview

• Status: Completed
• Conditions: Neutropenia
• Intervention / Treatment: Drug: Sporanox; Drug: Lozanoc

Detailed Description

After confirmation of eligibility, participants will be randomly assigned 1:1 to commence therapy with either 100mg mane and 100mg nocte for 21 days or Sporanox 200mg mane and 200mg nocte with food for 21 days. If a subject enters the study already receiving itraconazole prophylaxis at a dose of itraconazole higher than 100 mg twice a day, the subject will then be dosed on study at the pre-study dosage; that is, the subject will take the same number of capsules per day on study as the subject was taking prior to enrolment in the study.

The following information will be collected at baseline; whether the participant is taking itraconazole prophylaxis and at what dose; whether the participant is taking gastric suppression therapy. Patients who are not taking food or who are taking gastric acid suppression therapy (antacids, an H2 antagonist or a proton pump inhibitor) can take Sporanox with cola or orange juice to maximise absorption as recommended in the Sporanox product label (not required for Lozanoc formulation).

At Day 22, participants assigned to

• Lozanoc and who have completed 21 days of Lozanoc prophylaxis will cross over to the same number of Sporanox capsules with food for a further 21 days
• Sporanox and who have completed 21 days of Sporanox prophylaxis will cross over to the same number of Lozanoc capsules for a further 21 days.

The dose of either drug may be dose-reduced or ceased for toxicity at the discretion of the investigator.

During the course of the treatment periods participants will undergo the following assessments:

• Concurrent medication(s)
• Clinical adverse events
• Measurement of vital signs (weight, blood pressure, temperature)
• Targeted physical examination
• Documentation of any evidence of systemic fungal infection
• Medication and meal diaries
• 12-lead electrocardiogram (ECG)
• Laboratory safety assessments: Renal function and electrolytes (urea, creatinine, estimated glomerular filtration rate [eGFR], sodium, potassium, chloride, bicarbonate), Liver function tests (bilirubin, albumin, total protein, alanine aminotransferase [ALT], aspartate aminotransferase [AST])
• Pharmacokinetic testing: Trough (pre-morning dose; 0 hr) sample will be collected at Baseline (Day 1), and at Days 8, 15, 22, 29, 36 and 43. Post-dose samples will also be collected 2, 3.5 and 6 hours after the morning dose on Day 22 and Day 43

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 4

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • St Vincent's Hospital

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:

• Provision of written, informed consent
• Age of at least 18 years
• No clinical evidence of active systemic fungal infection
• Physician-recommended primary prophylaxis against systemic fungal infections with itraconazole in patients who have had or about to have: a heart, lung or bone marrow transplant, combination chemotherapy for cancer; aspergilloma, chronic pulmonary aspergillus bronchitis, or allergic bronchopulmonary aspergillosis
• Patients may be receiving itraconazole prophylaxis prior to entry into the study
• Body mass index between 15.0 and 35.0 kg/m2

Exclusion Criteria:

• Pregnant, planning pregnancy or breastfeeding
• Congestive cardiac failure or other causes of ventricular dysfunction that may outweigh the benefit of itraconazole
• Hypersensitivity to either study drug or to any of their excipients

• Coadministration of the following drugs:

  • CYP3A4 metabolised substrates that can prolong the QT-interval e.g., sertindole, terfenadine
  • CYP3A4 metabolised HMG-CoA reductase inhibitors e.g. simvastatin, lovastatin
  • Potent CYP3A4 inhibitors e.g. dronedarone
  • Triazolam, alprazolam and oral midazolam
  • Ergot alkaloids such as dihydroergotamine, ergometrine (ergonovine) and ergotamine

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Sporanox; 100 mg	Drug: Sporanox; At least 2 capsules twice a day for 3 weeks; Other Names: itraconazole
Experimental: Lozanoc; 50 mg	Drug: Lozanoc; At least 2 capsules twice a day for 3 weeks; Other Names: itraconazole

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Relative steady-state bioavailability	3 weeks

Collaborators and Investigators

• Sponsor: Mayne Pharma International Pty Ltd
• Investigators: Principal Investigator: Deborah Marriott, St Vincent's Hospital, Sydney

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2015
• Primary Completion (Actual): November 1, 2016
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: December 2, 2015
• First Submitted That Met QC Criteria: December 2, 2015
• First Posted (Estimate): December 4, 2015

Study Record Updates

• Last Update Posted (Actual): October 26, 2018
• Last Update Submitted That Met QC Criteria: October 24, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: Bioavailability; Prophylaxis; Steady-State
• Additional Relevant MeSH Terms: Hematologic Diseases; Agranulocytosis; Leukopenia; Leukocyte Disorders; Neutropenia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Itraconazole; Hydroxyitraconazole
• Other Study ID Numbers: MPG010

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Individual patient data will not be made available