Pharmacokinetics of Posaconazole (Noxafil®) as Prophylaxis for Invasive Fungal Infections

NCT02805946 | Completed Phase 4

• 2 other identifiers: UMCN-AKF16.012016-001182-87
• Study Type: interventional
• Target: 21
• Locations: 2 countries
• Sites: 2

Brief Summary

This study evaluates the the pharmacokinetics of posaconazole (new solid oral and IV) given as prophylaxis to patients who are at risk for developing fungal infections after receiving conditioning therapy (except strictly non-myeloablative (NMA)) for allogeneic Stem Cell Transplant (SCT), remission induction chemotherapy for acute myeloid leukemia (AML) or myelo dysplastic syndrome (MDS) or being treated for severe graft versus host disease (GvHD) and determines the impact of mucositis on the pharmacokinetics of posaconazole new solid oral.

Conditions

Allogeneic Stem Cell Transplant; Acute Graft Versus Host Disease; Acute Myeloid Leucaemia; Myelo Dysplastic Syndrome

Outcome Measures

Primary Outcomes (2)

• exposure to posaconazole (Area Under the Curve) when administered intravenously and orally (tablet formulation)

  Plasma samples drawn on t=0 (pre-dose), 0.5, 1 (just prior to end of infusion), 2, 3, 4, 6, 8, 10, 12, 18 and 24 hours post infusion or post intake will be taken op day 7, day 12 and day 16 to determine posaconazole concentrations. Area Under the Curve of two routes of administration and two dosing regimens will be determined.

  day 7, day 12 and day 16

• impact of mucositis (determined by citrulline concentrations) on exposure (AUC) to posaconazole.

  Full pharmacokinetic curve (plasma samples drawn on t=0 (pre-dose), 0.5, 1 (just prior to end of infusion), 2, 3, 4, 6, 8, 10, 12, 18 and 24 hours post infusion or post intake) will be taken op day 7, day 12 and day 16 (posaconazole). Impact of mucositis on oral absorption will be determined by comparing AUCs after intravenous administration with oral (tablet) administration in patients with mucositis.

  day 7, day 12 and day 16

Study Arms (2)

intravenous followed by oral

OTHER

* Start with posaconazole IV 300mg BID on the first day. Posaconazole will be infused over a period of 90 minutes. * Days 2-7 patients will receive posaconazole IV 300mg QD. * Days 8-12 patients will receive posaconazole PO 300mg QD. * Days 13-16 patients will receive posaconazole PO 200mg QD. * 3 PK curves will be determined on days 7, 12 and 16 (after the 7th, 12th and 16th dosage).

Drug: posaconazole

oral followed by intravenous

OTHER

* Start with posaconazole PO 300mg BID on the first day. * Days 2-7: patients will receive posaconazole PO 300mg QD. * Days 8-12: patients will receive posaconazole IV 300mg QD. Posaconazole will be infused over a period of 90 minutes. * Days 13-16 patients will receive posaconazole IV 200mg QD. * 3 PK curves will be determined on days 7, 12 and 16 (after the 7th, 12th and 16th dosage).

Drug: posaconazole

Interventions

posaconazole DRUG

iv versus oral

Also known as: Noxafil

intravenous followed by oral; oral followed by intravenous

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject is able and willing to sign the Informed Consent Form prior to screening evaluations.
• Subject is at least 18 years of age on the day of providing informed consent.
• Patient receives immunosuppressive therapy for acute or chronic GVHD grade II-IV, reduced intensity conditioning regimens for allogeneic stem cell transplant, or first remission induction chemotherapy for AML/MDS.
• In case of acute GVHD grade II-IV, patient has received less than 1 week of immunosuppressive therapy.
• If a woman, is neither pregnant nor able to become pregnant and is not nursing an infant.
• Has an ALAT \<200U/L, ALAT \<225U/L, alkaline phosphatase \<60 U/L and a bilirubin level \<50 μmol/L.
• Subject is capable of receiving oral tablets.
• Subject is managed with a central venous or arterial catheter.

You may not qualify if:

• Documented history of sensitivity to medicinal products or excipients similar to those found in the posaconazole preparation.
• Relevant history or presence of cardiovascular disorders (specifically QTc-time prolongation).
• Inability to understand the nature of the trial and the procedures required
• Any signs or symptoms of invasive fungal disease or the use of antifungal drugs within the previous month.
• Has previously participated in this trial.

Sponsors & Collaborators

• Radboud University Medical Center: lead
• Universitaire Ziekenhuizen KU Leuven: collaborator

Study Sites (2)

Universitaire Ziekenhuizen Leuven

Leuven, Belgium

Location

Radboudumc

Nijmegen, 6500HB, Netherlands

Location

MeSH Terms

Interventions

posaconazole

Study Officials

• Roger Brüggemann, PhD, PharmD

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 1, 2016
• First Posted: June 20, 2016
• Study Start: April 28, 2017
• Primary Completion: July 26, 2019
• Study Completion: September 7, 2019
• Last Updated: December 16, 2019

Record last verified: 2019-12

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1); NL (1)