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

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Primary Purpose

Status

Completed

Phase

Phase 1

Locations

Study Type

Interventional

Intervention

Posaconazole

About this trial

This is an interventional prevention trial for Fungal Infection

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Posaconazole

Arm Description

Posaconazole 300 mg tablet (3 x 100 mg tablets) once every 12 hours on Day 1 and once-daily on Days 2 to 28

Outcomes

Primary Outcome Measures

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.

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).

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).

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).

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.

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).

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).

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).

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.

Secondary Outcome Measures

Full Information

NCT ID

NCT02387983

First Posted

March 9, 2015

Last Updated

September 10, 2018

Sponsor

Merck Sharp & Dohme LLC

1. Study Identification

Unique Protocol Identification Number

NCT02387983

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2018

Overall Recruitment Status

Completed

Study Start Date

May 6, 2015 (Actual)

Primary Completion Date

May 2, 2016 (Actual)

Study Completion Date

May 2, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Merck Sharp & Dohme LLC

4. Oversight

Data Monitoring Committee

No

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Fungal Infection

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

65 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Posaconazole

Arm Type

Experimental

Arm Description

Posaconazole 300 mg tablet (3 x 100 mg tablets) once every 12 hours on Day 1 and once-daily on Days 2 to 28

Intervention Type

Drug

Intervention Name(s)

Posaconazole

Other Intervention Name(s)

MK-5592

Intervention Description

Posaconazole 300 mg solid oral tablet

Primary Outcome Measure Information:

Title

Steady-state Average Concentration (ssCavg) of Posaconazole on Day 8

Description

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.

Time Frame