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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00423267
First received: January 17, 2007
Last updated: April 28, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Coccidioidomycosis
Drug: Posaconazole
Drug: Fluconazole
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Controlled, Double-Blind, Double-Dummy, Two-Arm Study of Posaconazole vs Fluconazole in the Treatment of Coccidioidomycosis

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

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 [ Time Frame: 12 months ] [ Designated as safety issue: No ]

    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 [ Time Frame: 12 months ] [ Designated as safety issue: No ]

    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 [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Number of Participant Discontinuations Due to Adverse Events and/or Laboratory Evaluations of Safety in Period B [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Enrollment: 16
Study Start Date: May 2007
Study Completion Date: May 2009
Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Posaconazole
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.
Drug: Posaconazole
Posaconazole 400 mg orally (PO) (oral suspension 40 mg/mL) administered twice daily with meals or oral nutritional supplements for 12 months
Active Comparator: Fluconazole
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.
Drug: Fluconazole
Fluconazole 400 mg PO (given as two 200-mg oral encapsulated tablets) administered once daily for 12 months

  Eligibility

Ages Eligible for Study:   13 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00423267     History of Changes
Other Study ID Numbers: P04558
Study First Received: January 17, 2007
Results First Received: May 27, 2010
Last Updated: April 28, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Coccidioidomycosis
Coccidiosis
Mycoses
Parasitic Diseases
Protozoan Infections
Fluconazole
Posaconazole
14-alpha Demethylase Inhibitors
Anti-Infective Agents
Antifungal Agents
Antiparasitic Agents
Antiprotozoal Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Trypanocidal Agents

ClinicalTrials.gov processed this record on October 23, 2014