Pharmacokinetics, Safety, and Tolerability of Intravenous Posaconazole Solution Followed by Oral Posaconazole Suspension in Subjects at High Risk for Invasive Fungal Infections (P05520)
NCT ID: NCT01075984
Last Updated: 2017-11-13
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE1
279 participants
INTERVENTIONAL
2010-02-23
2012-11-20
Brief Summary
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Individuals who have been diagnosed by their physicians with a blood disease or cancer that can affect their infection-fighting white blood cells will be asked to participate in the trial. Since these blood diseases and their treatments can weaken the immune system, they may put these individuals at a high risk for getting a serious fungal infection of their internal organs or blood (invasive fungal infection). As these fungal infections can be hard to detect early and can be life-threatening, many physicians believe that individuals diagnosed with these diseases should receive antifungal therapy to try to lower their risk of getting this type of infection.
Enrollment into this study will take place in several stages (cohorts). The determination of which cohort an individual will be asked to participate in is based on which cohort is open at the site at the time the individual is approached to consider study participation.
Detailed Description
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Conditions
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Keywords
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Study Design
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RANDOMIZED
SINGLE_GROUP
PREVENTION
NONE
Study Groups
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POS IV 200 mg single dose (Cohort 0)
POS 200 mg IV single dose infused over 1.5 hours on Day 1 followed 12 hours later by POS oral 400 mg, then by POS oral 400 mg BID on Days 2 through 6 and a single morning dose on Day 7 (Cohort 0)
Posaconazole
Dextrose 5% in water (Cohort 0)
Placebo IV single dose infused over 1.5 hours on Day 1 followed 12 hours later by POS oral 400 mg, then by POS oral 400 mg BID on Days 2 through 6 and a single morning dose on Day 7 (Cohort 0)
Posaconazole
Dextrose 5% in water
POS IV 200 mg BID (Cohort 1)
POS 200 mg IV infused over 1.5 hours BID on Day 1, followed by POS 200 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 1)
Posaconazole
POS IV 300 mg BID (Cohort 2)
POS 300 mg IV infused over 1.5 hours BID on Day 1, followed by POS 300 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 2). After Day 5, POS IV was administered continuously or intermittently, depending on oral tolerability.
Posaconazole
POS IV 300 mg BID (Cohort 3)
POS 300 mg IV infused over 1.5 hours BID on Day 1, followed by POS 300 mg IV once daily on Days 2 through 5, then by POS 200 mg oral TID or POS 400 mg oral BID through Day 28, or POS 200-300 mg IV once daily as required (Cohort 3). After Day 5, POS IV was administered continuously or intermittently, depending on oral tolerability.
Posaconazole
Interventions
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Posaconazole
Dextrose 5% in water
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Disease definition for each subject: Anticipated (likely to develop within 3 days to 5 days) or documented prolonged neutropenia (absolute neutrophil count \[ANC\] \<500/mm\^3 \[0.5 x 10\^9/L\]) at Baseline and likely to last for at least 7 days due to:
* a. Standard intensive chemotherapy, anthracycline-based or other accepted regimen (excluding any investigational agent), for a new diagnosis of acute myelogenous leukemia (AML);
* b. Chemotherapy for AML in first relapse; or
* c. Therapy for myelodysplastic syndromes in transformation to AML or other diagnoses of secondary AML (therapy related, antecedent hematological disorders) or chronic myelogenous leukemia in blast crisis
* Disease definition for each Cohort 3 subject: In addition to subjects defined above, allogeneic hematopoietic stem cell transplant (HSCT) subjects may be randomized in either the pre-engraftment period (i.e., after they have received their conditioning regimen for the transplant, but while they are still neutropenic) or in the post-engraftment period if they are receiving immunosuppressive therapy for prevention or treatment of graft-versus-host disease (e.g., steroids, tacrolimus, cyclosporin, mycophenolate mofetil, and antithymocyte globulin).
Exclusion Criteria
* Excluded prior treatments. A subject must not have received systemic antifungal therapy (oral, intravenous, or inhaled) for the treatment of proven or probable IFI within 30 days of Enrollment.
* A subject must not have moderate or severe liver dysfunction at Baseline, defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels greater than three times the upper limit of normal (ULN), AND a total bilirubin level greater than two times the ULN. For Cohorts 1 and 2, a subject must not have a known or suspected history of Gilbert's disease.
* A subject must not have an electrocardiogram (ECG) with a prolonged QTc interval by manual reading: QTc greater than 500 msec.
* A subject must not have prior enrollment in this study, or other POS studies within 90 days of study entry.
* A subject must not have a known or suspected invasive or systemic fungal infection at Baseline. Those subjects receiving empiric anti-fungal therapy within 7 days prior to Baseline must have had a diagnostic work-up that ruled out a possible invasive fungal infection.
* A subject must not have creatinine clearance levels (measured or calculated) below 50 mL/min.
* A subject must not have a history of Type I hypersensitivity or idiosyncratic reactions to azole agents.
18 Years
ALL
No
Sponsors
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Merck Sharp & Dohme LLC
INDUSTRY
Responsible Party
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Countries
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References
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Maertens J, Cornely OA, Ullmann AJ, Heinz WJ, Krishna G, Patino H, Caceres M, Kartsonis N, Waskin H, Robertson MN. Phase 1B study of the pharmacokinetics and safety of posaconazole intravenous solution in patients at risk for invasive fungal disease. Antimicrob Agents Chemother. 2014 Jul;58(7):3610-7. doi: 10.1128/AAC.02686-13. Epub 2014 Apr 14.
Cornely OA, Robertson MN, Haider S, Grigg A, Geddes M, Aoun M, Heinz WJ, Raad I, Schanz U, Meyer RG, Hammond SP, Mullane KM, Ostermann H, Ullmann AJ, Zimmerli S, Van Iersel MLPS, Hepler DA, Waskin H, Kartsonis NA, Maertens J. Pharmacokinetics and safety results from the Phase 3 randomized, open-label, study of intravenous posaconazole in patients at risk of invasive fungal disease. J Antimicrob Chemother. 2017 Dec 1;72(12):3406-3413. doi: 10.1093/jac/dkx263.
Other Identifiers
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P05520
Identifier Type: -
Identifier Source: org_study_id