Back to resultsOral Posaconazole in High Risk Patients With Gastrointestinal Dysfunction (Study P05115)
Primary Purpose
Fungal Infection, Acute Myelogenous Leukemia, Neutropenia
Status
Completed
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Posaconazole
Sponsored by
About this trial
This is an interventional prevention trial for Fungal Infection focused on measuring Antifungal Agents, Anti-Infective Agents
Eligibility Criteria
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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
POS 200 mg TID Days 1-8 Followed by POS 200 mg TID Days 9-15
POS 200 mg TID Days 1-8 Followed by POS 400 mg BID Days 9-15
POS 200 mg TID Days 1-8 Followed by POS 400 mg TID Days 9-15
Arm Description
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.
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.
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.
Outcomes
Primary Outcome Measures
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.
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.
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.
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.
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.
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.
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00686543
Brief Title
Oral Posaconazole in High Risk Patients With Gastrointestinal Dysfunction (Study P05115)
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
March 2017
Overall Recruitment Status
Completed
Study Start Date
December 2007 (undefined)
Primary Completion Date
April 2009 (Actual)
Study Completion Date
April 2009 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Fungal Infection, Acute Myelogenous Leukemia, Neutropenia
Keywords
Antifungal Agents, Anti-Infective Agents
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
75 (Actual)
8. Arms, Groups, and Interventions
Arm Title
POS 200 mg TID Days 1-8 Followed by POS 200 mg TID Days 9-15
Arm Type
Experimental
Arm Description
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.
Arm Title
POS 200 mg TID Days 1-8 Followed by POS 400 mg BID Days 9-15
Arm Type
Experimental
Arm Description
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.
Arm Title
POS 200 mg TID Days 1-8 Followed by POS 400 mg TID Days 9-15
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Posaconazole
Other Intervention Name(s)
SCH 056592 - NOXAFIL®
Intervention Description
Posaconazole will be used for prophylaxis
Primary Outcome Measure Information:
Title
Mean POS Plasma Concentrations on Days 2, 3, and 8.
Description
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.
Time Frame
Predose (0 hour) and 5 hours postdose on Days 2, 3, and 8
Title
Mean POS Plasma Concentrations on Days 8 and 15 Stratified by Randomized Dosing Regimen
Description
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.
Time Frame
Predose (0 hour) and 5 hours postdose on Days 8 and 15
Title
Participants With a Mean POS Plasma Concentration ≥/<250 ng/mL on Day 3 and ≥/<500 ng/mL on Day 8
Description
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.
Time Frame
Predose (0 hour) and 5 hours postdose on Days 3 and 8
Title
Participants With a Mean POS Plasma Concentration ≥/<350 ng/mL on Day 3 and ≥/<700 ng/mL on Day 8
Description
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.
Time Frame
Predose (0 hour) and 5 hours postdose on Days 3 and 8
Title
Participants With a Mean POS Plasma Concentration ≥/<250 ng/mL on Day 8 and ≥/<500 ng/mL on Day 15
Description
Individual mean concentrations calculated as the average of observed concentrations at 0 hour (before the morning dose) and 5 hours after the morning dose.
Time Frame
Predose (0 hour) and 5 hours postdose on Days 8 and 15
Title
Participants With a Mean POS Plasma Concentration ≥/<350 ng/mL on Day 8 and ≥/<700 ng/mL on Day 15
Description
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.
Time Frame
Predose (0 hour) and 5 hours postdose on Days 8 and 15
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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
Citations:
PubMed Identifier
22290953
Citation
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.
Results Reference
result
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Oral Posaconazole in High Risk Patients With Gastrointestinal Dysfunction (Study P05115)
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