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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Fungal Infection, Acute Myelogenous Leukemia, Neutropenia

Intervention / Treatment
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* Drug: Posaconazole


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


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<br>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<br>* Posaconazole will be used for prophylaxis<br>* Other names: SCH 056592 - NOXAFIL®;|
| Experimental: POS 200 mg TID Days 1-8 Followed by POS 400 mg BID Days 9-15<br>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<br>* Posaconazole will be used for prophylaxis<br>* Other names: SCH 056592 - NOXAFIL®;|
| Experimental: POS 200 mg TID Days 1-8 Followed by POS 400 mg TID Days 9-15<br>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<br>* Posaconazole will be used for prophylaxis<br>* Other names: SCH 056592 - NOXAFIL®;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Antifungal Agents, Anti-Infective Agents