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

• ClinicalTrials.gov Identifier: NCT02387983
• Recruitment Status: Completed
• First Posted: March 13, 2015
• Results First Posted: July 14, 2017
• Last Update Posted: October 9, 2018
• Sponsor: Merck Sharp & Dohme Corp.
• Information provided by (Responsible Party): Merck Sharp & Dohme Corp.

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Fungal Infection	Drug: Posaconazole	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 65 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Pharmacokinetics and Safety of Solid Oral Posaconazole (MK-5592, POS) in Chinese Subjects at High Risk for Invasive Fungal Infections
• Actual Study Start Date: May 6, 2015
• Actual Primary Completion Date: May 2, 2016
• Actual Study Completion Date: May 2, 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: Posaconazole; Posaconazole 300 mg tablet (3 x 100 mg tablets) once every 12 hours on Day 1 and once-daily on Days 2 to 28	Drug: Posaconazole; Posaconazole 300 mg solid oral tablet; Other Name: MK-5592

Outcome Measures

Primary Outcome Measures :

1. Steady-state Average Concentration (ssCavg) of Posaconazole on Day 8 [ Time Frame: Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose 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.
2. Steady-state Area Under the Concentration-time Curve (ssAUC0-24hr) of Posaconazole on Day 8 [ Time Frame: Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose 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).
3. Steady-state Maximum Concentration (ssCmax) of Posaconazole on Day 8 [ Time Frame: Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose 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).
4. Steady-state Minimum Concentration (ssCmin) of Posaconazole on Day 8 [ Time Frame: Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose 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).
5. Time to Steady-state Maximum Concentration (ssTmax) of Posaconazole on Day 8 [ Time Frame: Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose 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.
6. AUC0-24hr of Posaconazole on Day 1 [ Time Frame: Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose 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).
7. Cmax of Posaconazole on Day 1 [ Time Frame: Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose 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).
8. Cmin of Posaconazole on Day 1 [ Time Frame: Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose 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).
9. Tmax of Posaconazole on Day 1 [ Time Frame: Pre-dose and 2, 4, 6, 8, 12, and 24 hours post-dose 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Sponsors and Collaborators

Merck Sharp & Dohme Corp.

Investigators

• Study Director: Medical Director; Merck Sharp & Dohme Corp.

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Liu K, Wu D, Li J, Chen H, Ning H, Zhao T, Dai H, Chen L, Mangin E, Winchell GA, Waskin H, Jiang J, Qiu Y, Zhao XM. Pharmacokinetics and Safety of Posaconazole Tablet Formulation in Chinese Participants at High Risk for Invasive Fungal Infection. Adv Ther. 2020 May;37(5):2493-2506. doi: 10.1007/s12325-020-01341-x. Epub 2020 Apr 22.

• Responsible Party: Merck Sharp & Dohme Corp.
• ClinicalTrials.gov Identifier: NCT02387983
• Other Study ID Numbers: 5592-117
• First Posted: March 13, 2015
• Results First Posted: July 14, 2017
• Last Update Posted: October 9, 2018
• Last Verified: September 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
• URL: http://engagezone.msd.com/ds_documentation.php

Additional relevant MeSH terms:

Infections; Communicable Diseases; Mycoses; Invasive Fungal Infections; Disease Attributes; Pathologic Processes; Bacterial Infections and Mycoses; Posaconazole; Antifungal Agents; Anti-Infective Agents; Trypanocidal Agents; Antiprotozoal Agents; Antiparasitic Agents; 14-alpha Demethylase Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Steroid Synthesis Inhibitors; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs