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

Primary Purpose

Aspergillosis

Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Posaconazole
Voriconazole
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Aspergillosis

Eligibility Criteria

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

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.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm 4

    Arm Type

    Experimental

    Active Comparator

    Experimental

    Active Comparator

    Arm Label

    Cohort 1: Posaconazole

    Cohort 1: Voriconazole

    Cohort 2: Posaconazole

    Cohort 2: Voriconazole

    Arm Description

    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

    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

    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

    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

    Outcomes

    Primary Outcome Measures

    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.

    Secondary Outcome Measures

    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.
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    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.

    Full Information

    First Posted
    July 1, 2014
    Last Updated
    January 11, 2021
    Sponsor
    Merck Sharp & Dohme LLC
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    1. Study Identification

    Unique Protocol Identification Number
    NCT02180165
    Brief Title
    Assessing the Safety and Efficacy of MK-5592 (Posaconazole) in Japanese Participants With Fungal Infection (MK-5592-101)
    Official Title
    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
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    January 2021
    Overall Recruitment Status
    Completed
    Study Start Date
    July 29, 2014 (Actual)
    Primary Completion Date
    January 24, 2018 (Actual)
    Study Completion Date
    January 24, 2018 (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 primary objective of this study is to assess and compare the safety of posaconazole with voriconazole in Japanese participants with aspergillosis.

    6. Conditions and Keywords

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

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    116 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Cohort 1: Posaconazole
    Arm Type
    Experimental
    Arm Description
    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
    Arm Title
    Cohort 1: Voriconazole
    Arm Type
    Active Comparator
    Arm Description
    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
    Arm Title
    Cohort 2: Posaconazole
    Arm Type
    Experimental
    Arm Description
    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
    Arm Title
    Cohort 2: Voriconazole
    Arm Type
    Active Comparator
    Arm Description
    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
    Intervention Type
    Drug
    Intervention Name(s)
    Posaconazole
    Intervention Description
    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
    Intervention Type
    Drug
    Intervention Name(s)
    Voriconazole
    Intervention Description
    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
    Primary Outcome Measure Information:
    Title
    Number of Participants With an Adverse Event
    Description
    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.
    Time Frame
    Up to approximately Day 98
    Secondary Outcome Measure Information:
    Title
    Percentage of Participants With Successful Overall Response for Invasive Aspergillosis in Cohort 2 at Day 42
    Description
    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.
    Time Frame
    Day 42
    Title
    Percentage of Participants With Successful Overall Response for Invasive Aspergillosis in Cohort 2 at Day 84
    Description
    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.
    Time Frame
    Day 84
    Title
    Percentage of Participants With Successful Overall Response for Chronic Pulmonary Aspergillosis in Cohort 2 at Day 42
    Description
    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.
    Time Frame
    Day 42
    Title
    Percentage of Participants With Successful Overall Response for Chronic Pulmonary Aspergillosis in Cohort 2 at Day 84
    Description
    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.
    Time Frame
    Day 84
    Title
    Percentage of Participants With Successful Overall Response for Invasive Aspergillosis and Chronic Pulmonary Aspergillosis in Cohort 2 at End of Trial (Day 84)
    Description
    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.
    Time Frame
    Day 84
    Title
    Percentage of Participants With Successful Overall Response for Zygomycosis in Cohort 2 at Day 42
    Description
    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.
    Time Frame
    Day 42
    Title
    Percentage of Participants With Successful Overall Response for Zygomycosis in Cohort 2 at Day 84
    Description
    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.
    Time Frame
    Day 84
    Title
    Percentage of Participants With Successful Overall Response for Invasive Aspergillosis in Cohort 2 at Day 42 as Assessed by the Clinical Investigator
    Description
    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.
    Time Frame
    Day 42
    Title
    Percentage of Participants With Successful Overall Response for Chronic Pulmonary Aspergillosis in Cohort 2 at Day 84 as Assessed by the Clinical Investigator
    Description
    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.
    Time Frame
    Day 84
    Title
    Percentage of Participants With Invasive Aspergillosis With Clinical Response of Resolution or Improvement in Cohort 2 at Day 42
    Description
    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.
    Time Frame
    Day 42
    Title
    Percentage of Participants With Invasive Aspergillosis With Clinical Response of Resolution or Improvement in Cohort 2 at Day 84
    Description
    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.
    Time Frame
    Day 84
    Title
    Percentage of Participants With Invasive Aspergillosis With Radiological Response of Resolution or Improvement in Cohort 2 at Day 42
    Description
    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.
    Time Frame
    Day 42
    Title
    Percentage of Participants With Invasive Aspergillosis With Radiological Response of Resolution or Improvement in Cohort 2 at Day 84
    Description
    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.
    Time Frame
    Day 84
    Title
    Percentage of Participants With Invasive Aspergillosis With Mycological Response of Eradication in Cohort 2 at Day 42
    Description
    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.
    Time Frame
    Day 42
    Title
    Percentage of Participants With Chronic Pulmonary Aspergillosis With Clinical Response of Resolution in Cohort 2 at Day 42
    Description
    A clinical response of resolution is defined as resolution of attributable signs and symptoms of disease, as assessed by the CAC.
    Time Frame
    Day 42
    Title
    Percentage of Participants With Chronic Pulmonary Aspergillosis With Clinical Response of Resolution in Cohort 2 at Day 84
    Description
    A clinical response of resolution is defined as resolution of attributable signs and symptoms of disease, as assessed by the CAC.
    Time Frame
    Day 84
    Title
    Percentage of Participants With Chronic Pulmonary Aspergillosis With Radiological Response of Resolution in Cohort 2 at Day 42
    Description
    A radiological response of resolution is defined as resolution of radiological lesions, as assessed by the CAC.
    Time Frame
    Day 42
    Title
    Percentage of Participants With Chronic Pulmonary Aspergillosis With Mycological Response of Eradication in Cohort 2 at Day 42
    Description
    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.
    Time Frame
    Day 42
    Title
    Percentage of Participants With Chronic Pulmonary Aspergillosis With Mycological Response of Eradication in Cohort 2 at Day 84
    Description
    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.
    Time Frame
    Day 84

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    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.
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Medical Director
    Organizational Affiliation
    Merck Sharp & Dohme LLC
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
    IPD Sharing URL
    http://engagezone.msd.com/ds_documentation.php
    Citations:
    Citation
    "Kohno S, Izumikawa K, Yoshida M, Okada F, Mori T, Najima Y, Waskin H, Shizuya T, Fukuhara T, Adachi N, Niki Y. A Randomized, Active-controlled, Open-label, Comparative Study to Assess the Safety and Efficacy of Posaconazole in Japanese Subjects with Deep-seated Fungal Infection. Nihon Ishinkin Gakkai Zasshi. 2020; 61(1):1-11. PDF file: https://www.jstage.jst.go.jp/article/ishinkin/61/1/61_19-00015/_pdf/-char/ja Web page: https://www.jstage.jst.go.jp/article/ishinkin/61/1/61_19-00015/_article/-char/ja"
    Results Reference
    result

    Learn more about this trial

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

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