POS vs FLU for First Line Treatment of Coccidioidomycosis (Study P04558Am1)(COMPLETED)
Condition: Coccidioidomycosis
MeSH terms: Coccidioidomycosis; Coccidiosis
Intervention: Posaconazole; Fluconazole
Intervention description: Posaconazole 400 mg orally (PO) (oral suspension 40 mg/mL) administered twice daily with meals or oral nutritional supplements for 12 months; Fluconazole 400 mg PO (given as two 200-mg oral encapsulated tablets) administered once daily for 12 months
Intervention MeSH terms: Fluconazole; Posaconazole
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 16.0
Sex: All
Minimum age: 13 Years
Healthy volunteers: No

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.
    

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.