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”

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.

Intervention(s) in this Clinical Trial

• Drug: Posaconazole
  • Posaconazole 400 mg orally (PO) (oral suspension 40 mg/mL) administered twice daily with meals or oral nutritional supplements for 12 months
• Drug: Fluconazole
  • Fluconazole 400 mg PO (given as two 200-mg oral encapsulated tablets) administered once daily for 12 months

Arms, Groups and Cohorts in this Clinical Trial

• 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.
• 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.

Primary 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
    Safety Issue?: No
• Number of Participants With Treatment-related Treatment-emergent Adverse Events (TRAEs) That Occurred With Posaconazole (POS) in Period B
  • Time Frame: 12 months
    Safety Issue?: No

Secondary Measures

• Number of Participants With Treatment-emergent Adverse Events (TEAEs)That Occurred With POS or FLU in Period A
  • Time Frame: 12 months
    Safety Issue?: No
• Number of Participants With Treatment-emergent Adverse Events (TEAEs) That Occurred With POS in Period B
  • Time Frame: 12 months
    Safety Issue?: No
• 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
    Safety Issue?: No
• 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
    Safety Issue?: No
• Number of Participant Discontinuations Due to Adverse Events and/or Laboratory Evaluations of Safety in Period A
  • Time Frame: 12 months
    Safety Issue?: No
• Number of Participant Discontinuations Due to Adverse Events and/or Laboratory Evaluations of Safety in Period B
  • Time Frame: 12 months
    Safety Issue?: No

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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 13 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Schering-Plough Industry

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00423267

Study ID Number: P04558

ClinicalTrials.gov Identifier: NCT00423267

Health Authority: United States: Food and Drug Administration