Pharmacokinetics and Safety of Posaconazole Tablet in Participants at High Risk for Invasive Fungal Infections (MK-5592-065/P05615)

NCT ID: NCT01777763

Last Updated: 2017-04-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 230 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-06-30
• Study Completion Date: 2012-02-29

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.

Conditions

Fungal Infections

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Posaconazole 200 mg

Posaconazole 200 mg (two 100 mg tablets) twice daily (BID) on Day 1 followed by 200 mg (two 100 mg tablets) once daily (QD) for up to 28 days

Group Type: EXPERIMENTAL

Posaconazole 200 mg

Intervention Type: DRUG

Posaconazole 300 mg

Posaconazole 300 mg (three 100 mg tablets) BID on Day 1 followed by 300 mg (three 100 mg tablets) QD for up to 28 days

Group Type: EXPERIMENTAL

Posaconazole 300 mg

Intervention Type: DRUG

Interventions

Posaconazole 200 mg

Intervention Type: DRUG

Posaconazole 300 mg

Intervention Type: DRUG

Other Intervention Names

SCH 056592; MK-5592; Noxafil®; SCH 056592; MK-5592; Noxafil®

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

References

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.

Reference Type: RESULT

PMID: 25049247 (View on PubMed)

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

Reference Type: RESULT

de Almeida C, Wong M, Kleijn HJ, Wrishko RE. Predicted Bezlotoxumab Exposure in Patients Who Have Received a Hematopoietic Stem Cell Transplant. Clin Ther. 2023 Apr;45(4):356-362. doi: 10.1016/j.clinthera.2023.02.006. Epub 2023 Mar 9.

Reference Type: DERIVED

PMID: 36906440 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 26612870 (View on PubMed)

Other Identifiers

2008-006684-36

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

5592-065

Identifier Type: OTHER

Identifier Source: secondary_id

P05615

Identifier Type: -

Identifier Source: org_study_id