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A Study of the Safety and Efficacy of Posaconazole Versus Voriconazole for the Treatment of Invasive Aspergillosis (MK-5592-069)

Primary Purpose

Fungal Infections, Invasive Pulmonary Aspergillosis

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

About this trial

This is an interventional treatment trial for Fungal Infections

Eligibility Criteria

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

Inclusion Criteria:

  • Weight >40 kg (88 lb) and ≤150 kg (330 lb); if between 13 and 14 years of age must weigh >= 50 kg (110 lb)
  • Must meet the criteria for proven, probable, or possible IA as per 2008 European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) disease definitions at the time of randomization. Proven IA will include those participants with the demonstration of fungal elements (by cytology, microscopy, or culture) in diseased tissue (sterile sampling). Probable IA includes participants with at least 1 host factor, clinical criteria, as well as mycological criteria including both direct and indirect methods. Possible IA includes participants with at least 1 host factor and clinical criteria but without mycological criteria. A modification to the 2008 EORTC/MSG criteria regarding risk factors has been made to allow for the inclusion of participants with any duration of neutropenia as an acceptable inclusion host factor.
  • If with possible IA at time of randomization must be willing or be in process of an ongoing diagnostic work up which is anticipated to result in a mycological diagnosis of proven or probable IA postrandomization.
  • Must have a central line (e.g., central venous catheter, peripherally-inserted central catheter, etc.) in place or planned to be in place prior to beginning IV study therapy. If without central catheter access, must be clinically stable and able to receive oral study therapy.
  • Acute IA defined as duration of clinical syndrome of <30 days.
  • Must be willing to adhere to dosing, study visit schedule, and mandatory procedures as outlined in the protocol. The participant must be willing to continue on study therapy for up to 12 weeks and remain in the study through the 1-month follow-up visit.
  • The participant must have the ability to transition to oral study therapy during the course of the study.
  • Female participants of child-bearing potential must be using a medically accepted method of birth control before beginning study-drug treatment and agree to continue its use for 30 days after stopping study medication
  • Is not taking prohibited antifungal prophylaxis or treatment

Exclusion Criteria:

  • Chronic (>1 month duration) IA, relapsed/recurrent IA, or refractory IA which has not responded to antifungal therapy.
  • Has pulmonary sarcoidosis, aspergilloma, or allergic bronchopulmonary aspergillosis (ABPA).
  • Known mixed invasive mold fungal infection including Zygomycetes, and/or a known invasive Aspergillus fungal infection in which either study drug may not be considered active.
  • Receipt of any systemic (oral, intravenous, or inhaled) antifungal therapy for this infection episode for 4 or more consecutive days (>= 96 hours) immediately before randomization.
  • Developed the current episode of IA infection during receipt of >13 days of antifungal prophylaxis with an agent considered to be a mold-active antifungal agent.
  • Receipt of posaconazole or voriconazole as empirical treatment for this infection for 4 days (96 hours) or more within the 15 days immediately before randomization.
  • Has condition that, in the opinion of the investigator, may interfere with optimal participation in the study.
  • Known hypersensitivity or other serious adverse reaction to any azole antifungal therapy or to any other ingredient of the study medication used.
  • Females who are pregnant, intend to become pregnant, or are nursing at the time of randomization.
  • Known history of Torsade de Pointes, unstable cardiac arrhythmia or proarrhythmic conditions, or a history of recent myocardial infarction within 90 days of study entry.
  • Has significant liver dysfunction
  • Hepatic cirrhosis or a Child-Pugh score of C (severe hepatic impairment) at the time of randomization.
  • Severe renal insufficiency (estimated creatinine clearance <20 mL/min) or on hemodialysis at the time of randomization or likely to require dialysis during the study.
  • Known hereditary problem of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption.
  • Acute symptomatic pancreatitis within 6 months of study entry or a diagnosis of chronic pancreatitis at the time of randomization.
  • Active skin lesion consistent with squamous cell carcinoma at the time of randomization, or a current or prior history of malignant melanoma within 5 years of study entry.
  • On artificial ventilation or receiving acute Continuous Positive Airway Pressure (CPAP)/Bilevel Positive Airway Pressure (BPAP) at the time of randomization.
  • Known or suspected Gilbert's disease at the time of randomization.
  • Requires treatment with other medications that cannot be stopped and for which there is a known contraindication to co-administration of one or more of the study drugs.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Active Comparator

    Arm Label

    Posaconazole (POS)

    Voriconazole

    Arm Description

    Participants received 300 mg posaconazole (POS) intravenous (IV) twice per day (BID) on Day 1, and then received 300 mg POS IV plus placebo IV once per day (QD) starting on Day 2 until clinically stable when participants transitioned to oral POS tablets plus oral placebo tablets QD for up to 12 weeks of treatment. Most participants were expected to initiate treatment with IV therapy and transition to oral therapy as clinically indicated, with some participants initiating treatment with oral therapy, per clinical judgment.

    Participants received 6 mg/kg voriconazole (VOR) IV twice per day (BID) on Day 1, and then received 4 mg/kg VOR IV BID on Day 2 until clinically stable when participants transitioned to oral therapy with VOR capsules or VOR placebo capsules BID for up to 12 weeks of treatment. Most participants were expected to initiate treatment with IV therapy and transition to oral therapy as clinically indicated, with some participants initiating treatment with oral therapy, per clinical judgment.

    Outcomes

    Primary Outcome Measures

    Percentage of Participants Who Died Through Day 42 in the Intention to Treat Population
    The percentage of participants who died with posaconazole (POS) compared to voriconazole (VOR) in the first line treatment of invasive aspergillosis (IA) in the Intention to Treat (ITT) population through Day 42 was assessed.

    Secondary Outcome Measures

    Percentage of Participants Who Died Through Day 42 in the Full Analysis Set Population
    The percentage of participants who died with POS compared to VOR in the first line treatment of invasive aspergillosis (IA) in the Full Analysis Set (FAS) population through Day 42 was assessed.
    Percentage of Participants Who Died Through Day 84 in the ITT Population
    The percentage of participants who died with POS compared to VOR in the first line treatment of invasive aspergillosis (IA) in the ITT population through Day 84 was assessed.
    Percentage of Participants Who Died Through Day 84 in the FAS Population
    The percentage of participants who died with POS compared to VOR in the first line treatment of invasive aspergillosis (IA) in the FAS population through Day 84 was assessed.
    Percentage of Participants Achieving Global Clinical Response at Week 12 in the FAS Population
    The global clinical response of POS compared to VOR in the first line treatment of invasive aspergillosis (IA) was assessed. The percentage of participants achieving adjudicated global clinical response (complete or partial) at Week 12 was reported. Complete response was classified as survival with resolution of fungal disease evidence; Partial response was survival and improvement of fungal disease.
    Percentage of Participants Achieving Global Clinical Response at Week 6 in the FAS Population
    The global clinical response of POS compared to VOR in the first line treatment of invasive aspergillosis (IA) was assessed. The percentage of participants achieving adjudicated global clinical response (complete or partial) at Week 6 was reported. Complete response was classified as survival with resolution of fungal disease evidence; Partial response was survival and improvement of fungal disease.
    Number of Participants Experiencing Mortality at Day 42, Day 84, and Day 114 in the FAS Population (Kaplan-Meier Time To Death Estimate)
    The number of participants experiencing mortality at Day 42, Day 84 and Day 114 in participants with proven or probable IA receiving POS versus VOR were assessed. The Kaplan-Meier estimate reports the number of participants who experienced death (all causes) through Day 114 or ~16 weeks. Participants who did not have any endpoint event until last visit or who were lost to follow-up and had no event were censored at the time of last available information (last study visit). For Day 42 and Day 84, missing or 'unable to determine' responses were considered as failures (dead).
    Number of Participants Who Died Due to Invasive Aspergillosis Through Day 42 in the FAS Population
    The number of participants who died due to IA receiving POS versus VOR through Day 42 was assessed.
    Number of Participants Who Died Due to Invasive Aspergillosis Through Day 84 in the FAS Population
    The number of participants who died due to IA receiving POS versus VOR in the FAS population through Day 84 was assessed.
    Percentage of Participants With Tier 1 Treatment Emergent Adverse Events
    The percentage of participants with Tier 1 treatment-emergent adverse events (TEAEs) was determined. The Tier 1 TEAEs included hepatic safety (elevated aspartate serum transaminase [AST] or alanine serum transaminase [ALT] value ≥3x upper limit of normal (ULN) and an elevated total bilirubin value ≥2x ULN and, at the same time, an alkaline phosphatase value <2 ULN); central nervous system (CNS) and visual disturbances (eye disorders, nervous system disorders, psychiatric disorders), dermatologic reactions, and adrenal insufficiency or temporally associated TEAEs of hypotension.
    Percentage of Participants With at Least One Adverse Event
    An adverse event (AE) was defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, 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.
    Percentage of Participants With at Least One Drug Related Adverse Event
    An adverse event (AE) was defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, 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.
    Percentage of Participants With at Least One Serious Adverse Event
    A serious adverse event (SAE) was an AE that resulted in death, was life threatening, required or prolonged an existing hospitalization, resulted in persistent or significant disability or incapacity, was a congenital anomaly or birth defect, or was another important medical event deemed such by medical or scientific judgment.
    Percentage of Participants With at Least One Serious Drug Related Adverse Event
    An SAE was an AE that resulted in death, was life threatening, required or prolonged an existing hospitalization, resulted in persistent or significant disability or incapacity, was a congenital anomaly or birth defect, or was another important medical event deemed such by medical or scientific judgment.
    Percentage of Participants Who Discontinued Study Treatment Due to an Adverse Event
    An AE was defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, 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.
    Steady State Average Concentration (Cavg) of Posaconazole With Food Intake
    The characterization of the pharmacokinetics (PK) parameters of POS was determined from plasma samples taken at steady-state after receiving oral tablet of POS. Steady-state Cavg, where Cavg is defined as area under the concentration time-curve from 0 to 24 hours (AUC0-24hr) divided by the dosing interval. Data is presented in POS group column only. No evaluation of food intake on the VOR capsule was presented.

    Full Information

    First Posted
    January 30, 2013
    Last Updated
    August 26, 2020
    Sponsor
    Merck Sharp & Dohme LLC
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    1. Study Identification

    Unique Protocol Identification Number
    NCT01782131
    Brief Title
    A Study of the Safety and Efficacy of Posaconazole Versus Voriconazole for the Treatment of Invasive Aspergillosis (MK-5592-069)
    Official Title
    A Phase 3 Randomized Study of the Efficacy and Safety of Posaconazole Versus Voriconazole for the Treatment of Invasive Aspergillosis in Adults and Adolescents (Phase 3; Protocol No. MK-5592-069)
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    August 2020
    Overall Recruitment Status
    Completed
    Study Start Date
    September 25, 2013 (Actual)
    Primary Completion Date
    July 10, 2019 (Actual)
    Study Completion Date
    September 10, 2019 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Merck Sharp & Dohme LLC

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    The purpose of this study is to evaluate the safety and efficacy of posaconazole (POS) versus voriconazole (VOR) in the treatment of adults and adolescents with invasive aspergillosis (IA). The primary hypothesis is that the all-cause mortality through Day 42 in the POS treatment group is non-inferior to that in the VOR treatment group.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Fungal Infections, Invasive Pulmonary Aspergillosis

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantCare ProviderInvestigatorOutcomes Assessor
    Allocation
    Randomized
    Enrollment
    585 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Posaconazole (POS)
    Arm Type
    Experimental
    Arm Description
    Participants received 300 mg posaconazole (POS) intravenous (IV) twice per day (BID) on Day 1, and then received 300 mg POS IV plus placebo IV once per day (QD) starting on Day 2 until clinically stable when participants transitioned to oral POS tablets plus oral placebo tablets QD for up to 12 weeks of treatment. Most participants were expected to initiate treatment with IV therapy and transition to oral therapy as clinically indicated, with some participants initiating treatment with oral therapy, per clinical judgment.
    Arm Title
    Voriconazole
    Arm Type
    Active Comparator
    Arm Description
    Participants received 6 mg/kg voriconazole (VOR) IV twice per day (BID) on Day 1, and then received 4 mg/kg VOR IV BID on Day 2 until clinically stable when participants transitioned to oral therapy with VOR capsules or VOR placebo capsules BID for up to 12 weeks of treatment. Most participants were expected to initiate treatment with IV therapy and transition to oral therapy as clinically indicated, with some participants initiating treatment with oral therapy, per clinical judgment.
    Intervention Type
    Drug
    Intervention Name(s)
    Posaconazole
    Other Intervention Name(s)
    SCH 056592, MK-5592, Noxafil®
    Intervention Description
    POS IV: Day 1: 300 mg BID Day 2-84: 300 mg QD POS oral: Day 1: 300 mg BID Day 2-84: 300 mg QD
    Intervention Type
    Drug
    Intervention Name(s)
    Voriconazole
    Other Intervention Name(s)
    VFEND®
    Intervention Description
    VOR IV: Day 1: 6 mg/kg per body weight administered BID Day 2-84: 4 mg/kg per body weight administered BID VOR oral: Day 1: 300 mg BID Day 2-84: 200 mg BID
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo
    Intervention Description
    Matching placebo received for Posaconazole (IV and oral) or Voriconazole (oral)
    Primary Outcome Measure Information:
    Title
    Percentage of Participants Who Died Through Day 42 in the Intention to Treat Population
    Description
    The percentage of participants who died with posaconazole (POS) compared to voriconazole (VOR) in the first line treatment of invasive aspergillosis (IA) in the Intention to Treat (ITT) population through Day 42 was assessed.
    Time Frame
    Up to ~42 days
    Secondary Outcome Measure Information:
    Title
    Percentage of Participants Who Died Through Day 42 in the Full Analysis Set Population
    Description
    The percentage of participants who died with POS compared to VOR in the first line treatment of invasive aspergillosis (IA) in the Full Analysis Set (FAS) population through Day 42 was assessed.
    Time Frame
    Up to ~42 days
    Title
    Percentage of Participants Who Died Through Day 84 in the ITT Population
    Description
    The percentage of participants who died with POS compared to VOR in the first line treatment of invasive aspergillosis (IA) in the ITT population through Day 84 was assessed.
    Time Frame
    Up to ~84 days
    Title
    Percentage of Participants Who Died Through Day 84 in the FAS Population
    Description
    The percentage of participants who died with POS compared to VOR in the first line treatment of invasive aspergillosis (IA) in the FAS population through Day 84 was assessed.
    Time Frame
    Up to ~ 84 days
    Title
    Percentage of Participants Achieving Global Clinical Response at Week 12 in the FAS Population
    Description
    The global clinical response of POS compared to VOR in the first line treatment of invasive aspergillosis (IA) was assessed. The percentage of participants achieving adjudicated global clinical response (complete or partial) at Week 12 was reported. Complete response was classified as survival with resolution of fungal disease evidence; Partial response was survival and improvement of fungal disease.
    Time Frame
    Up to 12 weeks (± 4 weeks)
    Title
    Percentage of Participants Achieving Global Clinical Response at Week 6 in the FAS Population
    Description
    The global clinical response of POS compared to VOR in the first line treatment of invasive aspergillosis (IA) was assessed. The percentage of participants achieving adjudicated global clinical response (complete or partial) at Week 6 was reported. Complete response was classified as survival with resolution of fungal disease evidence; Partial response was survival and improvement of fungal disease.
    Time Frame
    Up to 6 weeks (± 2 weeks)
    Title
    Number of Participants Experiencing Mortality at Day 42, Day 84, and Day 114 in the FAS Population (Kaplan-Meier Time To Death Estimate)
    Description
    The number of participants experiencing mortality at Day 42, Day 84 and Day 114 in participants with proven or probable IA receiving POS versus VOR were assessed. The Kaplan-Meier estimate reports the number of participants who experienced death (all causes) through Day 114 or ~16 weeks. Participants who did not have any endpoint event until last visit or who were lost to follow-up and had no event were censored at the time of last available information (last study visit). For Day 42 and Day 84, missing or 'unable to determine' responses were considered as failures (dead).
    Time Frame
    Up to ~16 weeks (± 2 weeks)
    Title
    Number of Participants Who Died Due to Invasive Aspergillosis Through Day 42 in the FAS Population
    Description
    The number of participants who died due to IA receiving POS versus VOR through Day 42 was assessed.
    Time Frame
    Up to 42 days
    Title
    Number of Participants Who Died Due to Invasive Aspergillosis Through Day 84 in the FAS Population
    Description
    The number of participants who died due to IA receiving POS versus VOR in the FAS population through Day 84 was assessed.
    Time Frame
    Up to 84 days
    Title
    Percentage of Participants With Tier 1 Treatment Emergent Adverse Events
    Description
    The percentage of participants with Tier 1 treatment-emergent adverse events (TEAEs) was determined. The Tier 1 TEAEs included hepatic safety (elevated aspartate serum transaminase [AST] or alanine serum transaminase [ALT] value ≥3x upper limit of normal (ULN) and an elevated total bilirubin value ≥2x ULN and, at the same time, an alkaline phosphatase value <2 ULN); central nervous system (CNS) and visual disturbances (eye disorders, nervous system disorders, psychiatric disorders), dermatologic reactions, and adrenal insufficiency or temporally associated TEAEs of hypotension.
    Time Frame
    Up to ~16 weeks (± 2 weeks)
    Title
    Percentage of Participants With at Least One Adverse Event
    Description
    An adverse event (AE) was defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, 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.
    Time Frame
    Up to ~16 weeks (± 2 weeks)
    Title
    Percentage of Participants With at Least One Drug Related Adverse Event
    Description
    An adverse event (AE) was defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, 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.
    Time Frame
    Up to ~16 weeks (± 2 weeks)
    Title
    Percentage of Participants With at Least One Serious Adverse Event
    Description
    A serious adverse event (SAE) was an AE that resulted in death, was life threatening, required or prolonged an existing hospitalization, resulted in persistent or significant disability or incapacity, was a congenital anomaly or birth defect, or was another important medical event deemed such by medical or scientific judgment.
    Time Frame
    Up to ~16 weeks (± 2 weeks)
    Title
    Percentage of Participants With at Least One Serious Drug Related Adverse Event
    Description
    An SAE was an AE that resulted in death, was life threatening, required or prolonged an existing hospitalization, resulted in persistent or significant disability or incapacity, was a congenital anomaly or birth defect, or was another important medical event deemed such by medical or scientific judgment.
    Time Frame
    Up to ~16 weeks (± 2 weeks)
    Title
    Percentage of Participants Who Discontinued Study Treatment Due to an Adverse Event
    Description
    An AE was defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, 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.
    Time Frame
    Up to ~12 weeks
    Title
    Steady State Average Concentration (Cavg) of Posaconazole With Food Intake
    Description
    The characterization of the pharmacokinetics (PK) parameters of POS was determined from plasma samples taken at steady-state after receiving oral tablet of POS. Steady-state Cavg, where Cavg is defined as area under the concentration time-curve from 0 to 24 hours (AUC0-24hr) divided by the dosing interval. Data is presented in POS group column only. No evaluation of food intake on the VOR capsule was presented.
    Time Frame
    Baseline, and at pre-dose on Day 7, Week 2, Week 4, Week 6, and Week 12

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    13 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Weight >40 kg (88 lb) and ≤150 kg (330 lb); if between 13 and 14 years of age must weigh >= 50 kg (110 lb) Must meet the criteria for proven, probable, or possible IA as per 2008 European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) disease definitions at the time of randomization. Proven IA will include those participants with the demonstration of fungal elements (by cytology, microscopy, or culture) in diseased tissue (sterile sampling). Probable IA includes participants with at least 1 host factor, clinical criteria, as well as mycological criteria including both direct and indirect methods. Possible IA includes participants with at least 1 host factor and clinical criteria but without mycological criteria. A modification to the 2008 EORTC/MSG criteria regarding risk factors has been made to allow for the inclusion of participants with any duration of neutropenia as an acceptable inclusion host factor. If with possible IA at time of randomization must be willing or be in process of an ongoing diagnostic work up which is anticipated to result in a mycological diagnosis of proven or probable IA postrandomization. Must have a central line (e.g., central venous catheter, peripherally-inserted central catheter, etc.) in place or planned to be in place prior to beginning IV study therapy. If without central catheter access, must be clinically stable and able to receive oral study therapy. Acute IA defined as duration of clinical syndrome of <30 days. Must be willing to adhere to dosing, study visit schedule, and mandatory procedures as outlined in the protocol. The participant must be willing to continue on study therapy for up to 12 weeks and remain in the study through the 1-month follow-up visit. The participant must have the ability to transition to oral study therapy during the course of the study. Female participants of child-bearing potential must be using a medically accepted method of birth control before beginning study-drug treatment and agree to continue its use for 30 days after stopping study medication Is not taking prohibited antifungal prophylaxis or treatment Exclusion Criteria: Chronic (>1 month duration) IA, relapsed/recurrent IA, or refractory IA which has not responded to antifungal therapy. Has pulmonary sarcoidosis, aspergilloma, or allergic bronchopulmonary aspergillosis (ABPA). Known mixed invasive mold fungal infection including Zygomycetes, and/or a known invasive Aspergillus fungal infection in which either study drug may not be considered active. Receipt of any systemic (oral, intravenous, or inhaled) antifungal therapy for this infection episode for 4 or more consecutive days (>= 96 hours) immediately before randomization. Developed the current episode of IA infection during receipt of >13 days of antifungal prophylaxis with an agent considered to be a mold-active antifungal agent. Receipt of posaconazole or voriconazole as empirical treatment for this infection for 4 days (96 hours) or more within the 15 days immediately before randomization. Has condition that, in the opinion of the investigator, may interfere with optimal participation in the study. Known hypersensitivity or other serious adverse reaction to any azole antifungal therapy or to any other ingredient of the study medication used. Females who are pregnant, intend to become pregnant, or are nursing at the time of randomization. Known history of Torsade de Pointes, unstable cardiac arrhythmia or proarrhythmic conditions, or a history of recent myocardial infarction within 90 days of study entry. Has significant liver dysfunction Hepatic cirrhosis or a Child-Pugh score of C (severe hepatic impairment) at the time of randomization. Severe renal insufficiency (estimated creatinine clearance <20 mL/min) or on hemodialysis at the time of randomization or likely to require dialysis during the study. Known hereditary problem of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption. Acute symptomatic pancreatitis within 6 months of study entry or a diagnosis of chronic pancreatitis at the time of randomization. Active skin lesion consistent with squamous cell carcinoma at the time of randomization, or a current or prior history of malignant melanoma within 5 years of study entry. On artificial ventilation or receiving acute Continuous Positive Airway Pressure (CPAP)/Bilevel Positive Airway Pressure (BPAP) at the time of randomization. Known or suspected Gilbert's disease at the time of randomization. Requires treatment with other medications that cannot be stopped and for which there is a known contraindication to co-administration of one or more of the study drugs.
    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:
    PubMed Identifier
    33549194
    Citation
    Maertens JA, Rahav G, Lee DG, Ponce-de-Leon A, Ramirez Sanchez IC, Klimko N, Sonet A, Haider S, Diego Velez J, Raad I, Koh LP, Karthaus M, Zhou J, Ben-Ami R, Motyl MR, Han S, Grandhi A, Waskin H; study investigators. Posaconazole versus voriconazole for primary treatment of invasive aspergillosis: a phase 3, randomised, controlled, non-inferiority trial. Lancet. 2021 Feb 6;397(10273):499-509. doi: 10.1016/S0140-6736(21)00219-1. Erratum In: Lancet. 2021 Aug 7;398(10299):490.
    Results Reference
    derived

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    A Study of the Safety and Efficacy of Posaconazole Versus Voriconazole for the Treatment of Invasive Aspergillosis (MK-5592-069)

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