Clinical trial NCT01777763: Pharmacokinetics and Safety of Posaconazole Tablet in Participants at High Risk for Invasive Fungal Infections (MK-5592-065/P05615)
Official title: Pharmacokinetics and Safety of Solid Oral Posaconazole (SCH 56592) in Subjects at High Risk for Invasive Fungal Infections (Phase 1b; Protocol No. P05615)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Fungal Infections
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2013-01-29
Enrollment: 230
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to collect pharmacokinetic (PK) information related to how well posaconazole tablet is distributed in the body and to determine the safety of this new formulation. The study consists of a Phase 1B study that includes participants with neutropenia undergoing chemotherapy for acute myelogenous leukemia (AML) or myelodysplasia (MDS) and a Phase 3 study that includes participants who are undergoing chemotherapy for AML or MDS and participants who are recipients of allogeneic hematopoietic stem cell transplant (HSCT).

Detailed description: Participants with a blood disease or cancer that can affect their infection-fighting white blood cells and those who have undergone a hematopoietic stem cell transplant (HSCT) and are receiving immunosuppressive therapy and have or are at risk of graft-vs-host disease (GVHD) are eligible for the study. These blood diseases and their treatments can weaken the immune system and may put individuals at high risk for a serious fungal infection of their internal organs or blood (invasive fungal infection). As these 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 (parts). The determination of which part a participant will be in is based on which part is open at the site at the time of enrollment.

Eligibility criteria: Inclusion Criteria:

* Body weight \>34 kg (75 lb) and of any race/ethnicity
* Able to swallow oral tablets whole
* Anticipated (likely to develop within 3-5 days) or documented neutropenia due to chemotherapy, chemotherapy for a new diagnosis of acute myelogenous leukemia (AML), or AML in first relapse; myelodysplastic syndromes (MDS) in transformation to AML; allogeneic hematopoietic stem cell transplant (HSCT) participants in the pre-engraftment period or in the post-engraftment period if they are receiving immunosuppressive therapy for graft versus host disease

Exclusion Criteria:

- Female must not be pregnant, must not intend to become pregnant

during the study, and must not be nursing

* History of hypersensitivity to azoles
* Moderate or severe liver dysfunction 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
* Electrocardiogram (ECG) with corrected QTc interval greater than 500 msec
* Posaconazole within 10 days before study enrollment
* Receipt of systemic antifungal therapy within 30 days of study enrollment for reasons other than antifungal prophylaxis
* Evidence of known or suspected invasive or systemic fungal infection at baseline
* Known or suspected history of Gilbert's disease
* Creatinine clearance levels below 30 mL/min

Primary outcomes:
measure: Average Concentration (Cavg) of Posaconazole Tablet
timeFrame: Predose on Day 1 up to 24 hours postdose on Day 8
measure: Minimum Concentration (Cmin) of Posaconazole Tablet
timeFrame: Predose on Day 1 up to 24 hours postdose on Day 8
measure: Maximum Concentration (Cmax) of Posaconazole Tablet
timeFrame: Predose on Day 1 up to 24 hours postdose on Day 8
measure: Time to Maximum Concentration (Tmax) of Posaconazole Tablet
timeFrame: Predose on Day 1 up to 24 hours postdose on Day 8
measure: Apparent Total Body Clearance (CL/F) for Posaconazole Tablet
timeFrame: Predose on Day 1 up to 24 hours postdose on Day 8
Secondary outcomes:
Other outcomes:
measure: Number of Participants Surviving at Day 65
timeFrame: Day 65
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs)
timeFrame: Up to Day 65
measure: Number of Participants With Treatment-Related AEs
timeFrame: Up to Day 65
measure: Number of Participants Discontinuing Study Treatment Due to an AE
timeFrame: Up to Day 28
Locations:
Study officials:
References:
citation: Duarte RF, Lopez-Jimenez J, Cornely OA, Laverdiere M, Helfgott D, Haider S, Chandrasekar P, Langston A, Perfect J, Ma L, van Iersel ML, Connelly N, Kartsonis N, Waskin H. Phase 1b study of new posaconazole tablet for prevention of invasive fungal infections in high-risk patients with neutropenia. Antimicrob Agents Chemother. 2014 Oct;58(10):5758-65. doi: 10.1128/AAC.03050-14. Epub 2014 Jul 21.
citation: Cornely OA, Duarte RF, Haider S, Chandrasakar P, Helfgott D, Lopez J, Candoni A, Raad I, Laverdiere M, Langston A, Van Iersel M, Connelly N, Waskin H. Phase 3 Pharmacokinetics and Safety Study of Posaconazole Tablet in Patients at Risk for Invasive Fungal Infection. J Antimicrob Chemother. 2015;[e-pub 26Nov2015]. doi: 10.1093/jac/dkv380
citation: Cornely OA, Duarte RF, Haider S, Chandrasekar P, Helfgott D, Jimenez JL, Candoni A, Raad I, Laverdiere M, Langston A, Kartsonis N, Van Iersel M, Connelly N, Waskin H. Phase 3 pharmacokinetics and safety study of a posaconazole tablet formulation in patients at risk for invasive fungal disease. J Antimicrob Chemother. 2016 Mar;71(3):718-26. doi: 10.1093/jac/dkv380. Epub 2015 Nov 26.