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

NCT01777763 | Completed Phase 1 Results DMC

• 3 other identifiers: P056152008-006684-365592-065
• Study Type: interventional
• Target: 230
• Locations: 0 countries
• Sites: N/A

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).

Conditions

Fungal Infections

Outcome Measures

Primary Outcomes (5)

• Average Concentration (Cavg) of Posaconazole Tablet

  Posaconazole steady-state concentrations of posaconazole in the plasma reached after regular and repeated dosing were used to estimate pharmacokinetic (PK) parameters for each participant where Cavg was defined as area under the plasma concentration versus time curve divided by the dosing interval. Blood samples for the assessment of Cavg were collected on Day 1 and Day 8 predose and then at specified time points up to 24 hours postdose.

  Predose on Day 1 up to 24 hours postdose on Day 8

• Minimum Concentration (Cmin) of Posaconazole Tablet

  Cmin was defined as posaconazole trough level immediately before a participant received the dose of posaconazole tablets on the specified day. Trough (Cmin) level blood samples for determination of posaconazole in plasma were collected for all participants on Day 1, Day 2, Day 3, and Day 8. On Day 1, the trough level sample was collected the before the first dose of study drug. On Day 2, trough samples were collected approximately 12 hours after the second dose of study drug was administered on Day 1. On all subsequent days, trough samples were collected approximately 24 hours following the previous day's dose of study drug.

  Predose on Day 1 up to 24 hours postdose on Day 8

• Maximum Concentration (Cmax) of Posaconazole Tablet

  Blood samples for the assessment of Cmax were collected on Day 1 and Day 8 predose and then at specified time points up to 24 hours postdose.

  Predose on Day 1 up to 24 hours postdose on Day 8

• Time to Maximum Concentration (Tmax) of Posaconazole Tablet

  Blood samples for the assessment of Tmax were collected on Day 1 and Day 8 predose and then at specified time points up to 24 hours postdose.

  Predose on Day 1 up to 24 hours postdose on Day 8

• Apparent Total Body Clearance (CL/F) for Posaconazole Tablet

  Blood samples for the assessment of CL/F, the rate at which posaconazole was removed from the body, were collected on Day 1 and Day 8 predose and then at specified time points up to 24 hours postdose.

  Predose on Day 1 up to 24 hours postdose on Day 8

Other Outcomes (4)

• Number of Participants Surviving at Day 65

  Day 65

• Number of Participants With Treatment-Emergent Adverse Events (AEs)

  Up to Day 65

• Number of Participants With Treatment-Related AEs

  Up to Day 65

Study Arms (2)

Posaconazole 200 mg

EXPERIMENTAL

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

Drug: Posaconazole 200 mg

Posaconazole 300 mg

EXPERIMENTAL

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

Drug: Posaconazole 300 mg

Interventions

Posaconazole 200 mg DRUG

Also known as: SCH 056592, MK-5592, Noxafil®

Posaconazole 200 mg

Posaconazole 300 mg DRUG

Also known as: SCH 056592, MK-5592, Noxafil®

Posaconazole 300 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• \- 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (4)

• 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.

  PMID: 25049247 RESULT

• 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

  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.

  PMID: 36906440 DERIVED

• 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.

  PMID: 26612870 DERIVED

MeSH Terms

Conditions

Mycoses

Interventions

posaconazole

Condition Hierarchy (Ancestors)

Bacterial Infections and Mycoses; Infections

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 25, 2013
• First Posted: January 29, 2013
• Study Start: June 1, 2009
• Primary Completion: February 1, 2012
• Study Completion: February 1, 2012
• Last Updated: April 7, 2017
• Results First Posted: March 28, 2013

Record last verified: 2017-03

Data Sharing

• IPD Sharing: Will share