Assessing the Safety and Efficacy of MK-5592 (Posaconazole) in Japanese Participants With Fungal Infection (MK-5592-101)

Study Overview
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Brief Summary
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The primary objective of this study is to assess and compare the safety of posaconazole with voriconazole in Japanese participants with aspergillosis.

Official Title
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A Randomized, Comparative, Open-label Study to Assess the Safety and Efficacy of MK-5592 Compared With Voriconazole in Japanese Subjects With Deep-seated Fungal Infection

Conditions
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Aspergillosis

Intervention / Treatment
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* Drug: Posaconazole
* Drug: Voriconazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body weight >=45 kg Can be treated by taking tablet orally or intravenous (IV) formulation via central vein Female has a negative pregnancy test Female of non-childbearing potential; or if of childbearing potential, agrees to use proper combination of barrier method of birth control Met screening criteria for either Invasive aspergillosis, chronic pulmonary aspergillosis, zygomycosis or fusariosis. Exclusion Criteria: Has a fungal infection other than Aspergillus any species (spp.) Zygomycetes (including Mucor spp.) and Fusarium spp. infection Has allergic bronchopulmonary aspergillosis, allergic sinusitis of aspergillosis, or aspergillosis of the eye Has long-term inactive aspergilloma not expected to respond to investigational product Is not expected to survive study duration Has an underlying disease, complication and systemic condition which makes it difficult to evaluate effect of study drug Has received, or continues to receive any systemic antifungal therapy, and cannot discontinue this treatment; but if fungal infection does not improve, can switch to study drug Is expected to need prohibited medications Has received posaconazole, has received voriconazole for this infection in the past and has deep-seated fungal infection that has not responded to this treatment, has intolerance for azole antifungal treatments, or is receiving antifungal combination therapy for chronic pulmonary aspergillosis Has known hypersensitivity to any medication Has history of either Torsade de Pointes, myocardial infarction within previous 90 days, has congenital or acquired long QT interval syndrome, or unstable cardiac arrhythmia Has significant liver dysfunction Has liver cirrhosis or cholestasis Has renal insufficiency Has a known hereditary problem of either galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption Has acute symptomatic pancreatitis within 6 months of study entry or chronic pancreatitis Has an active skin lesion consistent with squamous cell carcinoma or melanoma, or within prior 5 years a history of malignant melanoma Has known or suspected Gilbert's disease Female is pregnant, or nursing, or intends to become pregnant within 14 days after end of study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: Posaconazole<br>300 mg posaconazole oral tablet (or 300 mg intravenous (IV) solution) twice on Day 1, followed by 300 mg oral tablet or IV solution once daily for up to 84 days | Drug: Posaconazole<br>* 300 mg posaconazole twice on Day 1, either by oral tablet or IV solution; followed by 300 mg once daily for up to 84 days<br>|
| Active Comparator: Cohort 1: Voriconazole<br>300 mg voriconazole oral tablet (or 6 mg/kg IV solution) twice on Day 1, followed by 200 mg oral tablet (or 4 mg/kg IV solution) twice daily for up to 84 days | Drug: Voriconazole<br>* 300 mg voriconazole oral tablet (or 6 mg/kg IV solution) twice on Day 1, followed by 200 mg oral tablet (or 4 mg/kg IV solution) twice daily for up to 84 days<br>|
| Experimental: Cohort 2: Posaconazole<br>300 mg posaconazole oral tablet (or 300 mg intravenous (IV) solution) twice on Day 1, followed by 300 mg oral tablet or IV solution once daily for up to 84 days | Drug: Posaconazole<br>* 300 mg posaconazole twice on Day 1, either by oral tablet or IV solution; followed by 300 mg once daily for up to 84 days<br>|
| Active Comparator: Cohort 2: Voriconazole<br>300 mg voriconazole oral tablet (or 6 mg/kg IV solution) twice on Day 1, followed by 200 mg oral tablet (or 4 mg/kg IV solution) twice daily for up to 84 days | Drug: Voriconazole<br>* 300 mg voriconazole oral tablet (or 6 mg/kg IV solution) twice on Day 1, followed by 200 mg oral tablet (or 4 mg/kg IV solution) twice daily for up to 84 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With an Adverse Event | An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol specified procedure, whether or not considered related to the medicinal product or protocol specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of the Sponsor's product is also an AE. | Up to approximately Day 98 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Successful Overall Response for Invasive Aspergillosis in Cohort 2 at Day 42 | Successful treatment (or successful overall response) is defined as complete response and partial response to treatment assessed by the clinical adjudication committee (CAC). The 95% confidence interval (CI) is based on the Clopper-Pearson exact method. | Day 42 | 
| Percentage of Participants With Successful Overall Response for Invasive Aspergillosis in Cohort 2 at Day 84 | Successful treatment (or successful overall response) is defined as complete response and partial response to treatment assessed by CAC. The 95% CI is based on the Clopper-Pearson exact method. | Day 84 | 
| Percentage of Participants With Successful Overall Response for Chronic Pulmonary Aspergillosis in Cohort 2 at Day 42 | Successful treatment (or successful overall response) is defined as favorable response to treatment assessed by CAC. The 95% CI is based on the Clopper-Pearson exact method. | Day 42 | 
| Percentage of Participants With Successful Overall Response for Chronic Pulmonary Aspergillosis in Cohort 2 at Day 84 | Successful treatment (or successful overall response) is defined as favorable response to treatment assessed by CAC. The 95% CI is based on the Clopper-Pearson exact method. | Day 84 | 
| Percentage of Participants With Successful Overall Response for Invasive Aspergillosis and Chronic Pulmonary Aspergillosis in Cohort 2 at End of Trial (Day 84) | Successful treatment (or successful overall response) for invasive aspergillosis is defined as complete response and partial response to treatment assessed by CAC. Successful treatment (or successful overall response) for chronic pulmonary aspergillosis is defined as favorable response to treatment.The 95% CI is based on the Clopper-Pearson exact method. | Day 84 | 
| Percentage of Participants With Successful Overall Response for Zygomycosis in Cohort 2 at Day 42 | Zygomycosis is an infection caused by zygomycete fungi. Successful treatment (or successful overall response) is defined as complete response and partial response to treatment assessed by CAC. The 95% CI is based on the Clopper-Pearson exact method. | Day 42 | 
| Percentage of Participants With Successful Overall Response for Zygomycosis in Cohort 2 at Day 84 | Zygomycosis is an infection caused by zygomycete fungi. Successful treatment (or successful overall response) is defined as complete response and partial response to treatment assessed by CAC. The 95% CI is based on the Clopper-Pearson exact method. | Day 84 | 
| Percentage of Participants With Successful Overall Response for Invasive Aspergillosis in Cohort 2 at Day 42 as Assessed by the Clinical Investigator | Successful treatment (or successful overall response) for invasive aspergillosis is defined as complete response and partial response to treatment assessed by the clinical investigator.The 95% CI is based on the Clopper-Pearson exact method. | Day 42 | 
| Percentage of Participants With Successful Overall Response for Chronic Pulmonary Aspergillosis in Cohort 2 at Day 84 as Assessed by the Clinical Investigator | Successful treatment (or successful overall response) for chronic pulmonary aspergillosis is defined as favorable response to treatment assessed by the clinical investigator.The 95% CI is based on the Clopper-Pearson exact method. | Day 84 | 
| Percentage of Participants With Invasive Aspergillosis With Clinical Response of Resolution or Improvement in Cohort 2 at Day 42 | A clinical response of resolution is defined as resolution of attributable signs and symptoms of disease, and a clinical response of improvement is defined as improvement of attributable signs and symptoms of disease as assessed by the CAC. | Day 42 | 
| Percentage of Participants With Invasive Aspergillosis With Clinical Response of Resolution or Improvement in Cohort 2 at Day 84 | A clinical response of resolution is defined as resolution of attributable signs and symptoms of disease, and a clinical response of improvement is defined as improvement of attributable signs and symptoms of disease as assessed by the CAC. | Day 84 | 
| Percentage of Participants With Invasive Aspergillosis With Radiological Response of Resolution or Improvement in Cohort 2 at Day 42 | A radiological response of resolution is defined as resolution of radiological lesions, and a radiological response of improvement is defined as major reduction in size of radiological lesions as assessed by the CAC. | Day 42 | 
| Percentage of Participants With Invasive Aspergillosis With Radiological Response of Resolution or Improvement in Cohort 2 at Day 84 | A radiological response of resolution is defined as resolution of radiological lesions, and a radiological response of improvement is defined as major reduction in size of radiological lesions as assessed by the CAC. | Day 84 | 
| Percentage of Participants With Invasive Aspergillosis With Mycological Response of Eradication in Cohort 2 at Day 42 | A mycological response of eradication is defined as fungus detected from culture or microscopy at the screening is eradicated at the time of evaluation (including presumed eradication), as assessed by the CAC. | Day 42 | 
| Percentage of Participants With Chronic Pulmonary Aspergillosis With Clinical Response of Resolution in Cohort 2 at Day 42 | A clinical response of resolution is defined as resolution of attributable signs and symptoms of disease, as assessed by the CAC. | Day 42 | 
| Percentage of Participants With Chronic Pulmonary Aspergillosis With Clinical Response of Resolution in Cohort 2 at Day 84 | A clinical response of resolution is defined as resolution of attributable signs and symptoms of disease, as assessed by the CAC. | Day 84 | 
| Percentage of Participants With Chronic Pulmonary Aspergillosis With Radiological Response of Resolution in Cohort 2 at Day 42 | A radiological response of resolution is defined as resolution of radiological lesions, as assessed by the CAC. | Day 42 | 
| Percentage of Participants With Chronic Pulmonary Aspergillosis With Mycological Response of Eradication in Cohort 2 at Day 42 | A mycological response of eradication is defined as fungus detected from culture or microscopy at the screening is eradicated at the time of evaluation (including presumed eradication), as assessed by the CAC. | Day 42 | 
| Percentage of Participants With Chronic Pulmonary Aspergillosis With Mycological Response of Eradication in Cohort 2 at Day 84 | A mycological response of eradication is defined as fungus detected from culture or microscopy at the screening is eradicated at the time of evaluation (including presumed eradication), as assessed by the CAC. | Day 84 |