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

Fungal Infections Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01777763
• Other study ID #: P05615
• Secondary ID: 2008-006684-3655
• Status: Completed
• Phase: Phase 1
• First received: January 25, 2013
• Last updated: January 25, 2016
• Start date: June 2009
• Est. completion date: February 2012

Study information

• Verified date: January 2016
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 230
• Est. completion date: February 2012
• Est. primary completion date: February 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Fungal Infections
• Infection
• Mycoses

Intervention

Drug:
• Posaconazole 200 mg

• Posaconazole 300 mg

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

References & Publications (2)

Cornely OA, Duarte RF, Haider S, Chandrasekar P, Helfgott D, Jiménez 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 patien — View Citation

Duarte RF, López-Jiménez 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 infectio — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of Participants Surviving at Day 65	Number of Participants Alive at Day 65	Day 65	Yes
Other	Number of Participants With Treatment-Emergent Adverse Events (AEs)	AEs are any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a study drug, whether or not considered related to this study drug. Treatment-emergent AEs are any events not present before starting study drug treatment or any events that were present before treatment that worsened in either intensity or frequency after exposure to study drug.	Up to Day 65	Yes
Other	Number of Participants With Treatment-Related AEs	AEs are any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a study drug, whether or not considered related to this study drug. Treatment-related AEs were considered by the investigator to be related to the study drug.	Up to Day 65	Yes
Other	Number of Participants Discontinuing Study Treatment Due to an AE	AEs are any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a study drug, whether or not considered related to this study drug. These AEs resulted in participants stopping study drug treatment. This measure includes participants who discontinued due to AEs and also includes treatment failures that were attributed to AEs.	Up to Day 28	Yes
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No