Oral Posaconazole in High Risk Patients With Gastrointestinal Dysfunction (Study P05115)

A Phase 4 Study of the Pharmacokinetics of Oral Posaconazole (SCH 56592) Among Patients With Compromised Gastrointestinal Function and at High Risk for Invasive Fungal Infection

The purpose of this study is: to explore the potential for different dosing strategies of posaconazole oral suspension (POS) to increase plasma levels and to profile the pharmacokinetics of these dosing strategies in patients with compromised gastrointestinal function and at high risk for Invasive Fungal Infection.

Study Overview

• Status: Completed
• Conditions: Fungal Infection; Neutropenia; Acute Myelogenous Leukemia
• Intervention / Treatment: Drug: Posaconazole

• Study Type: Interventional
• Enrollment (Actual): 75
• 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:

• Subjects >=18 years of age
• High risk of poor enteral medication absorption, based on the effects of cytotoxic chemotherapy, as evidenced by, but not limited to, mucositis, nausea, vomiting, and diarrhea, at baseline.
• High risk of invasive fungal infection (IFI) based on anticipated or documented prolonged neutropenia (absolute neutrophil count [ANC] <500/mm^3 [0.5 x 10^9/L]).
• Clinical laboratory safety tests within normal limits or clinically acceptable to the investigator or sponsor.
• Free of any clinically significant disease (other than the primary hematologic disease) that would interfere with the study evaluations.
• Subjects must be willing to give written informed consent and able to adhere to dosing, study visit schedule, and mandatory procedures.

Exclusion Criteria:

• Female subjects who are pregnant, intend to become pregnant, or are nursing.
• Excluded prior treatments. Subjects receiving systemic antifungal therapy (oral, intravenous, or inhaled) for the treatment of proven or probable IFI within 30 days of Enrollment (ie, voriconazole, fluconazole [FLU], or itraconazole [ITZ]).
• Subjects receiving posaconazole for prophylaxis against IFI 10 days prior to enrollment. (Subjects who are receiving either voriconazole or micafungin for prophylaxis against IFI should discontinue those therapies upon enrollment.)
• Subjects with moderate or severe liver dysfunction at Baseline, defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels greater than two times the upper limit of normal (ULN), or a total bilirubin level greater than two times the ULN.
• Subjects who have taken prohibited medications more recently than the indicated washout period prior to Enrollment.
• Subjects who must take prohibited medications during the study.
• Subjects who are in a situation or have any condition that, in the opinion of the investigator, may interfere with optimal participation in the study.
• Subjects who have used any investigational drugs or biologic agents other than their chemotherapy regimens within 30 days of study entry.
• Subjects who are part of the staff personnel directly involved with this study.
• Subjects who are a family member of the investigational study staff.
• Prior enrollment in this study.
• Subjects with a history of hypersensitivity or idiosyncratic reactions to azole agents.
• Subjects with Eastern Cooperative Oncology Group (ECOG) performance status >2 prior to induction chemotherapy for their underlying disease.
• Subjects with proven or probable invasive or systemic fungal infection at Baseline.
• Subjects with a history of acute lymphoblastic leukemia or chronic myelogenous leukemia without blast crisis.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: POS 200 mg TID Days 1-8 Followed by POS 200 mg TID Days 9-15; POS 200 mg three times a day (TID) on Days 1-8 followed by continued randomized dosing regimen of POS 200 mg TID on Days 9-15, administered with food or oral nutritional supplements.	Drug: Posaconazole; Posaconazole will be used for prophylaxis; Other Names: SCH 056592 - NOXAFIL®
Experimental: POS 200 mg TID Days 1-8 Followed by POS 400 mg BID Days 9-15; POS 200 mg TID on Days 1-8 followed by randomized dosing regimen of POS 400 mg twice a day (BID) on Days 9-15, administered with food or oral nutritional supplements.	Drug: Posaconazole; Posaconazole will be used for prophylaxis; Other Names: SCH 056592 - NOXAFIL®
Experimental: POS 200 mg TID Days 1-8 Followed by POS 400 mg TID Days 9-15; POS 200 mg TID on Days 1-8 followed by randomized dosing regimen of POS 400 mg TID on Days 9-15, administered with food or oral nutritional supplements.	Drug: Posaconazole; Posaconazole will be used for prophylaxis; Other Names: SCH 056592 - NOXAFIL®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean POS Plasma Concentrations on Days 2, 3, and 8.	Individual mean concentrations were calculated as the average of observed concentrations at 0 hour (before the morning dose) and 5 hours after the morning dose.	Predose (0 hour) and 5 hours postdose on Days 2, 3, and 8
Mean POS Plasma Concentrations on Days 8 and 15 Stratified by Randomized Dosing Regimen	Individual mean concentrations were calculated as the average of observed concentrations at 0 hour (before the morning dose) and 5 hours after the morning dose.	Predose (0 hour) and 5 hours postdose on Days 8 and 15
Participants With a Mean POS Plasma Concentration ≥/<250 ng/mL on Day 3 and ≥/<500 ng/mL on Day 8	Individual mean concentrations were calculated as the average of observed concentrations at 0 hour (before the morning dose) and 5 hours after the morning dose.	Predose (0 hour) and 5 hours postdose on Days 3 and 8
Participants With a Mean POS Plasma Concentration ≥/<350 ng/mL on Day 3 and ≥/<700 ng/mL on Day 8	Individual mean concentrations were calculated as the average of observed concentrations at 0 hour (before the morning dose) and 5 hours after the morning dose.	Predose (0 hour) and 5 hours postdose on Days 3 and 8
Participants With a Mean POS Plasma Concentration ≥/<250 ng/mL on Day 8 and ≥/<500 ng/mL on Day 15	Individual mean concentrations calculated as the average of observed concentrations at 0 hour (before the morning dose) and 5 hours after the morning dose.	Predose (0 hour) and 5 hours postdose on Days 8 and 15
Participants With a Mean POS Plasma Concentration ≥/<350 ng/mL on Day 8 and ≥/<700 ng/mL on Day 15	Individual mean concentrations were calculated as the average of observed concentrations at 0 hour (before the morning dose) and 5 hours after the morning dose.	Predose (0 hour) and 5 hours postdose on Days 8 and 15

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Cornely OA, Helfgott D, Langston A, Heinz W, Vehreschild JJ, Vehreschild MJ, Krishna G, Ma L, Huyck S, McCarthy MC. Pharmacokinetics of different dosing strategies of oral posaconazole in patients with compromised gastrointestinal function and who are at high risk for invasive fungal infection. Antimicrob Agents Chemother. 2012 May;56(5):2652-8. doi: 10.1128/AAC.05937-11. Epub 2012 Jan 30.

Study record dates

Study Major Dates

• Study Start: December 1, 2007
• Primary Completion (Actual): April 1, 2009
• Study Completion (Actual): April 1, 2009

Study Registration Dates

• First Submitted: May 27, 2008
• First Submitted That Met QC Criteria: May 29, 2008
• First Posted (Estimate): May 30, 2008

Study Record Updates

• Last Update Posted (Actual): April 7, 2017
• Last Update Submitted That Met QC Criteria: March 9, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Anti-Infective Agents; Antifungal Agents
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Bacterial Infections and Mycoses; Agranulocytosis; Leukopenia; Leukocyte Disorders; Leukemia; Infections; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Mycoses; Neutropenia; 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: P05115; EudraCT No. 2007-003148-31

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf

http://engagezone.msd.com/ds_documentation.php