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 efficacy of posaconazole (POS) in the treatment of coccidioidomycosis by comparing POS to fluconazole (FLU) after 6 months of treatment based on a standardized scoring system ("Mycoses Study Group [MSG] Coccidioidomycosis Scoring System").

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Active Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: May 2009

Intervention(s) in this Clinical Trial

• Drug: Posaconazole
  • Posaconazole 400 mg 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: 1
  • 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 PO (oral suspension 40 mg/mL) administered twice daily with meals or oral nutritional supplements for 12 months.
• Active Comparator: 2
  • 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

Primary Measures

• Successful response rate at Month 6, where a successful response is defined as ≥50% reduction from the baseline score at the completion of 6 months of initially assigned therapy in the MSG Coccidioidomycosis Scoring System.
  • Time Frame: Six months
    Safety Issue?: No

Secondary Measures

• Successful response rate at Month 12 where a successful response is defined as ≥50% reduction from the baseline score at the completion of 12 months of initially assigned therapy in the MSG Coccidioidomycosis Scoring System. Time to successful response
  • Time Frame: Twelve months
    Safety Issue?: No

Inclusion Criteria:

• Thirteen years of age or older, 34 kg (75 lb) or more, either sex, and any race;
• C. immitis or 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 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;
• CD4 count of <200 cells/mm3 or any AIDS-defining illness in HIV-positive subjects in the prior 30 days.
• Excluded Baseline Laboratory Studies
• Moderate or severe liver dysfunction (AST or ALT > 5 times 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 (CrCl <20 mL/min) or dialysis required or expected to be required within the study period;
• 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 Sponsor: Schering-Plough

Overall Clinical Trial Officials and Contacts

Antonino Catanzaro, MD Principal Investigator UCSD Medical Center  

Information obtained from ClinicalTrials.gov on October 06, 2008

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