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POS vs FLU for First Line Treatment of Coccidioidomycosis (Study P04558Am1)(COMPLETED)

Primary Purpose

Coccidioidomycosis

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

About this trial

This is an interventional treatment trial for Coccidioidomycosis

Eligibility Criteria

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

Inclusion Criteria:

  • Thirteen years of age or older, 34 kg (75 lb) or more, either sex, and any race;
  • Coccidioides immitis (C. immitis) or Coccidioides posadasii (C. posadasii) identified by culture or microscopic examination from skeletal disease, chronic active pulmonary disease, or soft tissue disease;
  • Coccidioidomycosis score of >=6;
  • Clinical laboratory safety tests within normal limits or clinically acceptable to the sponsor;
  • Free of any clinically significant disease that would interfere with study evaluations;
  • Willing to give written informed consent and able to adhere to study medication dose, mandatory procedures (including human immunodeficiency virus (HIV) testing), and visit schedules;
  • Able to swallow food or a nutritional supplement;
  • Use of a medically accepted method of contraception;
  • Negative serum pregnancy test at Screening and negative urine pregnancy test at Randomization;
  • Women of childbearing potential not currently sexually active must agree to use a medically accepted method of contraception should they become sexually active while participating in the study.

Exclusion Criteria:

  • Key Exclusion Criteria

Excluded Medications at Enrollment

  • Medications that are known to interact with POS or FLU and that may lead to serious or life threatening side effects within 7 days prior to initiating study drug;
  • Medications known to lower the serum concentration/efficacy of azole antifungals within 7 days prior to study drug start;
  • Prior investigational drug use or biologic product administration within 30 days before study drug start;
  • Prior antifungal treatment for the current episode of infection with a total cumulative dose of >=8 g of any azole, >=4 mg/kg of amphotericin B deoxycholate, or >=20 mg/kg of lipid amphotericin B;
  • Antiretrovirals that are substrates of CYP3A4 administered to HIV-positive subjects, as it is not currently known how POS or FLU may affect such drugs or the potential to cause adverse reactions.

    • Excluded Concomitant Conditions
  • Immediately life-threatening coccidioidomycosis;
  • Confirmed or suspected meningeal coccidioidomycosis;
  • Pulmonary coccidioidomycosis in HIV-negative subjects for less than 3 months;
  • Any condition requiring use of prohibited drugs;
  • Cluster of Differentiation 4 (CD4) count of <200 cells/mm3 or any auto-immune deficiency syndrome (AIDS)-defining illness in HIV-positive subjects in the prior 30 days.

    • Excluded Baseline Laboratory Studies
  • Moderate or severe liver dysfunction (aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 5 times upper limit of normal (ULN)) or a total bilirubin level or direct bilirubin > 3 times ULN plus ALT or AST >2 times ULN (Hy's Rule);
  • Moderate or severe renal dysfunction (creatinine clearance (CrCl) <20 mL/min) or dialysis required or expected to be required within the study period;
  • Electrocardiogram (ECG) with a prolonged QTc interval by manual reading: QTc >450 msec for males and QTc >470 msec for females.

    • General Exclusion Criteria
  • Prior enrollment in this study or other POS studies;
  • Failed treatment with FLU or POS at any time in the past;
  • History of hypersensitivity or idiosyncratic reactions to azole drug therapy;
  • Women who are pregnant, intend to become pregnant, or are breast-feeding;
  • Situation or condition that may interfere with optimal participation in the study;

Part of the staff personnel directly involved with this study;

  • Family member of the investigational study staff.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Active Comparator

    Arm Label

    Posaconazole

    Fluconazole

    Arm Description

    Eligible subjects will be stratified at Baseline by disease site (skeletal, lung, or soft tissue) and by immune status (immunocompromised or non-immunocompromised) and will then be randomly assigned to receive Posaconazole 400 mg orally (PO) (oral suspension 40 mg/mL) administered twice daily with meals or oral nutritional supplements for 12 months.

    Eligible subjects will be stratified at Baseline by disease site (skeletal, lung, or soft tissue) and by immune status (immunocompromised or non-immunocompromised) and will then be randomly assigned to receive Fluconazole 400 mg PO (given as two 200-mg oral encapsulated tablets) administered once daily for 12 months. Fluconazole treatment or placebo only occurred during Period A.

    Outcomes

    Primary Outcome Measures

    Number of Participants With Treatment-related Treatment-emergent Adverse Events (TRAEs) That Occurred With Posaconazole (POS) or Fluconazole (FLU) in Period A
    Treatment-emergent adverse events are defined as new events that occur following subject entry into the study or events that worsen following study entry state. Treatment-related adverse events are defined as new events that occur following subject entry into the study or events that worsen following study entry state and are judged by the investigator to be possibly, probably or definitely related to study medication.
    Number of Participants With Treatment-related Treatment-emergent Adverse Events (TRAEs) That Occurred With Posaconazole (POS) in Period B
    Treatment-emergent adverse events are defined as new events that occur following subject entry into the study or events that worsen following study entry state. Treatment-related adverse events are defined as new events that occur following subject entry into the study or events that worsen following study entry state and are judged by the investigator to be possibly, probably or definitely related to study medication.

    Secondary Outcome Measures

    Number of Participants With Treatment-emergent Adverse Events (TEAEs)That Occurred With POS or FLU in Period A
    Treatment-emergent adverse events are defined as new events that occur following subject entry into the study or events that worsen following study entry state.
    Number of Participants With Treatment-emergent Adverse Events (TEAEs) That Occurred With POS in Period B
    Treatment-emergent adverse events are defined as new events that occur following subject entry into the study or events that worsen following study entry state.
    Number of Participants With Laboratory Test Abnormalities (at Least a 1 Grade Shift From Baseline) That Occurred With POS or FLU in Period A
    Severity grading was based on Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0. This is a descriptive terminology which can be utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term. CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE; Grade 2 Moderate AE; Grade 3 Severe AE; Grade 4 Life-threatening or disabling AE; Grade 5 Death related to AE.
    Number of Participants With Laboratory Abnormalities (at Least a 1 Grade Shift From Baseline) That Occurred With POS in Period B
    Severity grading was based on Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0. This is a descriptive terminology which can be utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term. CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE; Grade 2 Moderate AE; Grade 3 Severe AE; Grade 4 Life-threatening or disabling AE; Grade 5 Death related to AE.
    Number of Participant Discontinuations Due to Adverse Events and/or Laboratory Evaluations of Safety in Period A
    Number of Participant Discontinuations Due to Adverse Events and/or Laboratory Evaluations of Safety in Period B

    Full Information

    First Posted
    January 17, 2007
    Last Updated
    March 13, 2017
    Sponsor
    Merck Sharp & Dohme LLC
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00423267
    Brief Title
    POS vs FLU for First Line Treatment of Coccidioidomycosis (Study P04558Am1)(COMPLETED)
    Official Title
    A Multicenter, Randomized, Controlled, Double-Blind, Double-Dummy, Two-Arm Study of Posaconazole vs Fluconazole in the Treatment of Coccidioidomycosis
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    March 2017
    Overall Recruitment Status
    Completed
    Study Start Date
    May 2007 (undefined)
    Primary Completion Date
    May 2009 (Actual)
    Study Completion Date
    May 2009 (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
    To evaluate the safety of posaconazole (POS) in the treatment of coccidioidomycosis. Period A consisted of 2 blinded arms, posaconazole and fluconazole. Recruitment was stopped, and participants in Period A may have been eligible to roll over to an open-label, non-comparitive Period B. During Period B, participants received posaconazole for a treatment duration not to exceed 12 months.

    6. Conditions and Keywords

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

    7. Study Design

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

    8. Arms, Groups, and Interventions

    Arm Title
    Posaconazole
    Arm Type
    Experimental
    Arm Description
    Eligible subjects will be stratified at Baseline by disease site (skeletal, lung, or soft tissue) and by immune status (immunocompromised or non-immunocompromised) and will then be randomly assigned to receive Posaconazole 400 mg orally (PO) (oral suspension 40 mg/mL) administered twice daily with meals or oral nutritional supplements for 12 months.
    Arm Title
    Fluconazole
    Arm Type
    Active Comparator
    Arm Description
    Eligible subjects will be stratified at Baseline by disease site (skeletal, lung, or soft tissue) and by immune status (immunocompromised or non-immunocompromised) and will then be randomly assigned to receive Fluconazole 400 mg PO (given as two 200-mg oral encapsulated tablets) administered once daily for 12 months. Fluconazole treatment or placebo only occurred during Period A.
    Intervention Type
    Drug
    Intervention Name(s)
    Posaconazole
    Intervention Description
    Posaconazole 400 mg orally (PO) (oral suspension 40 mg/mL) administered twice daily with meals or oral nutritional supplements for 12 months
    Intervention Type
    Drug
    Intervention Name(s)
    Fluconazole
    Intervention Description
    Fluconazole 400 mg PO (given as two 200-mg oral encapsulated tablets) administered once daily for 12 months
    Primary Outcome Measure Information:
    Title
    Number of Participants With Treatment-related Treatment-emergent Adverse Events (TRAEs) That Occurred With Posaconazole (POS) or Fluconazole (FLU) in Period A
    Description
    Treatment-emergent adverse events are defined as new events that occur following subject entry into the study or events that worsen following study entry state. Treatment-related adverse events are defined as new events that occur following subject entry into the study or events that worsen following study entry state and are judged by the investigator to be possibly, probably or definitely related to study medication.
    Time Frame
    12 months
    Title
    Number of Participants With Treatment-related Treatment-emergent Adverse Events (TRAEs) That Occurred With Posaconazole (POS) in Period B
    Description
    Treatment-emergent adverse events are defined as new events that occur following subject entry into the study or events that worsen following study entry state. Treatment-related adverse events are defined as new events that occur following subject entry into the study or events that worsen following study entry state and are judged by the investigator to be possibly, probably or definitely related to study medication.
    Time Frame
    12 months
    Secondary Outcome Measure Information:
    Title
    Number of Participants With Treatment-emergent Adverse Events (TEAEs)That Occurred With POS or FLU in Period A
    Description
    Treatment-emergent adverse events are defined as new events that occur following subject entry into the study or events that worsen following study entry state.
    Time Frame
    12 months
    Title
    Number of Participants With Treatment-emergent Adverse Events (TEAEs) That Occurred With POS in Period B
    Description
    Treatment-emergent adverse events are defined as new events that occur following subject entry into the study or events that worsen following study entry state.
    Time Frame
    12 months
    Title
    Number of Participants With Laboratory Test Abnormalities (at Least a 1 Grade Shift From Baseline) That Occurred With POS or FLU in Period A
    Description
    Severity grading was based on Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0. This is a descriptive terminology which can be utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term. CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE; Grade 2 Moderate AE; Grade 3 Severe AE; Grade 4 Life-threatening or disabling AE; Grade 5 Death related to AE.
    Time Frame
    12 months
    Title
    Number of Participants With Laboratory Abnormalities (at Least a 1 Grade Shift From Baseline) That Occurred With POS in Period B
    Description
    Severity grading was based on Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0. This is a descriptive terminology which can be utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term. CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE; Grade 2 Moderate AE; Grade 3 Severe AE; Grade 4 Life-threatening or disabling AE; Grade 5 Death related to AE.
    Time Frame
    12 months
    Title
    Number of Participant Discontinuations Due to Adverse Events and/or Laboratory Evaluations of Safety in Period A
    Time Frame
    12 months
    Title
    Number of Participant Discontinuations Due to Adverse Events and/or Laboratory Evaluations of Safety in Period B
    Time Frame
    12 months

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    13 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Thirteen years of age or older, 34 kg (75 lb) or more, either sex, and any race; Coccidioides immitis (C. immitis) or Coccidioides posadasii (C. posadasii) identified by culture or microscopic examination from skeletal disease, chronic active pulmonary disease, or soft tissue disease; Coccidioidomycosis score of >=6; Clinical laboratory safety tests within normal limits or clinically acceptable to the sponsor; Free of any clinically significant disease that would interfere with study evaluations; Willing to give written informed consent and able to adhere to study medication dose, mandatory procedures (including human immunodeficiency virus (HIV) testing), and visit schedules; Able to swallow food or a nutritional supplement; Use of a medically accepted method of contraception; Negative serum pregnancy test at Screening and negative urine pregnancy test at Randomization; Women of childbearing potential not currently sexually active must agree to use a medically accepted method of contraception should they become sexually active while participating in the study. Exclusion Criteria: Key Exclusion Criteria Excluded Medications at Enrollment Medications that are known to interact with POS or FLU and that may lead to serious or life threatening side effects within 7 days prior to initiating study drug; Medications known to lower the serum concentration/efficacy of azole antifungals within 7 days prior to study drug start; Prior investigational drug use or biologic product administration within 30 days before study drug start; Prior antifungal treatment for the current episode of infection with a total cumulative dose of >=8 g of any azole, >=4 mg/kg of amphotericin B deoxycholate, or >=20 mg/kg of lipid amphotericin B; Antiretrovirals that are substrates of CYP3A4 administered to HIV-positive subjects, as it is not currently known how POS or FLU may affect such drugs or the potential to cause adverse reactions. Excluded Concomitant Conditions Immediately life-threatening coccidioidomycosis; Confirmed or suspected meningeal coccidioidomycosis; Pulmonary coccidioidomycosis in HIV-negative subjects for less than 3 months; Any condition requiring use of prohibited drugs; Cluster of Differentiation 4 (CD4) count of <200 cells/mm3 or any auto-immune deficiency syndrome (AIDS)-defining illness in HIV-positive subjects in the prior 30 days. Excluded Baseline Laboratory Studies Moderate or severe liver dysfunction (aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 5 times upper limit of normal (ULN)) or a total bilirubin level or direct bilirubin > 3 times ULN plus ALT or AST >2 times ULN (Hy's Rule); Moderate or severe renal dysfunction (creatinine clearance (CrCl) <20 mL/min) or dialysis required or expected to be required within the study period; Electrocardiogram (ECG) with a prolonged QTc interval by manual reading: QTc >450 msec for males and QTc >470 msec for females. General Exclusion Criteria Prior enrollment in this study or other POS studies; Failed treatment with FLU or POS at any time in the past; History of hypersensitivity or idiosyncratic reactions to azole drug therapy; Women who are pregnant, intend to become pregnant, or are breast-feeding; Situation or condition that may interfere with optimal participation in the study; Part of the staff personnel directly involved with this study; Family member of the investigational study staff.

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf http://engagezone.msd.com/ds_documentation.php

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    POS vs FLU for First Line Treatment of Coccidioidomycosis (Study P04558Am1)(COMPLETED)

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