Pharmacokinetics and Safety of Oral Posaconazole (MK-5592)Tablets in Chinese Participants at High Risk for Invasive Fungal Infections (MK-5592-117)

Fungal Infection Clinical Trial

Official title:

Pharmacokinetics and Safety of Solid Oral Posaconazole (MK-5592, POS) in Chinese Subjects at High Risk for Invasive Fungal Infections

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02387983
• Other study ID #: 5592-117
• Status: Completed
• Phase: Phase 1
• Start date: May 6, 2015
• Est. completion date: May 2, 2016

Study information

• Verified date: September 2018
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the pharmacokinetics and safety of oral posaconazole tablets in Chinese participants at high risk for invasive fungal infections. Neutropenic participants undergoing chemotherapy for acute myelogenous leukemia or myelodysplastic syndromes will be enrolled in the study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 65
• Est. completion date: May 2, 2016
• Est. primary completion date: May 2, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Chinese participant

• Female of reproductive potential with a serum hCG level consistent with a nongravid state and agree to use 2 acceptable methods of birth control throughout the study

• Body Mass Index (BMI) >=15 and <=30 kg/m^2

• Anticipated or documented prolonged neutropenia 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

• Free from any clinically significant disease other than the primary hematologic disease that would interfere with administration of study medication or study evaluations

Exclusion Criteria:

• Pregnant, intends to become pregnant during the study, or has been nursing

• Mentally or legally incapacitated, has significant emotional problems, or has clinically significant psychiatric disorder over the last 5 years

• Received systemic antifungal therapy (oral, intravenous, or inhaled) within 30 days of study enrollment for reasons other than antifungal prophylaxis

• Known or suspected invasive or systemic fungal infection

• Taken posaconazole within 10 days prior to study enrollment

• Major surgery, donated or lost 1 unit of blood, or participated in another investigational study within 4 weeks prior to the study

• Type 1 hypersensitivity or idiosyncratic reactions to azole agents

• Significant multiple or severe allergies, or has had an anaphylactic reaction or significant intolerability to drugs or food

• Moderate or severe liver dysfunction

• Chronic active hepatitis, cirrhosis, Hepatocellular Carcinoma (HCC), or other hepatic disease caused by a virus

• Previous electrocardiogram with a prolonged QTc interval

• Prior enrollment in this study or other posaconazole studies within 90 days of study entry

• Eastern Cooperative Oncology Group (ECOG) performance status was >2 prior to induction chemotherapy for the underlying disease

• Known or suspected Gilbert's disease

Related Conditions & MeSH terms

• Communicable Diseases
• Fungal Infection
• Infection
• Invasive Fungal Infections
• Mycoses

Intervention

Drug:
• Posaconazole
Posaconazole 300 mg solid oral tablet

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Steady-state Average Concentration (ssCavg) of Posaconazole on Day 8	The ssCavg was calculated in order to determine the percentage of participants achieving the pharmacokinetic (PK) target of ssCavg >500 ng/mL on Day 8 when plasma drug levels had reached steady state.	Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose on Day 8
Primary	Steady-state Area Under the Concentration-time Curve (ssAUC0-24hr) of Posaconazole on Day 8	The ssAUC0-24hr was calculated to determine the mean plasma drug concentration in the Intensive and Sparse PK subgroup from immediately after dosing to 24 hours post-dose on Day 8. Results data are presented as the arithmetic mean (% arithmetic coefficient of variation [CV]), where CV is calculated as (100 x standard deviation/arithmetic mean).	Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose on Day 8
Primary	Steady-state Maximum Concentration (ssCmax) of Posaconazole on Day 8	The ssCmax was calculated in order to determine the maximum post-dose plasma drug concentration in the Intensive and Sparse PK subgroup on Day 8. Results data are presented as the arithmetic mean (% arithmetic coefficient of variation [CV]), where CV is calculated as (100 x standard deviation/arithmetic mean).	Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose on Day 8
Primary	Steady-state Minimum Concentration (ssCmin) of Posaconazole on Day 8	The ssCmin was calculated in order to determine the lowest measurable drug concentration in the Intensive and Sparse PK subgroup up to 24 hours post-dose on Day 8. Results data are presented as the arithmetic mean (% arithmetic coefficient of variation [CV]), where CV is calculated as (100 x standard deviation/arithmetic mean).	Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose on Day 8
Primary	Time to Steady-state Maximum Concentration (ssTmax) of Posaconazole on Day 8	The ssTmax was calculated in order to determine the amount of time required to reach ssCmax in the Intensive and Sparse PK subgroup on Day 8.	Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose on Day 8
Primary	AUC0-24hr of Posaconazole on Day 1	The AUC0-24hr was calculated to determine the mean plasma drug concentration from immediately after dosing to 24 hours post-dose in the Immediate and Sparse PK subgroup on Day 1. Results data are presented as the arithmetic mean (% arithmetic coefficient of variation [CV]), where CV is calculated as (100 x standard deviation/arithmetic mean).	Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose on Day 1
Primary	Cmax of Posaconazole on Day 1	The Cmax was calculated to determine the maximum plasma drug concentration up to 24 hours post-dose in the Immediate and Sparse PK subgroup on Day 1. Results data are presented as the arithmetic mean (% arithmetic coefficient of variation [CV]), where CV is calculated as (100 x standard deviation/arithmetic mean).	Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose on Day 1
Primary	Cmin of Posaconazole on Day 1	The Cmin was calculated in order to determine the lowest measurable drug concentration from immediately after dosing to 24 hours post-dose in the Immediate and Sparse PK subgroup on Day 1. Results data are presented as the arithmetic mean (% arithmetic coefficient of variation [CV]), where CV is calculated as (100 x standard deviation/arithmetic mean).	Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose on Day 1
Primary	Tmax of Posaconazole on Day 1	The Tmax was calculated in order to determine the time required to reach Cmax in the Immediate and Sparse PK subgroup on Day 1.	Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose on Day 1