POS vs FLU for First Line Treatment of Coccidioidomycosis (Study P04558)

Condition(s) targeted: Coccidioidomycosis

Intervention: Posaconazole (Drug); Fluconazole (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: Schering-Plough

Official(s) and/or principal investigator(s):
Antonino Catanzaro, MD, Principal Investigator, Affiliation: UCSD Medical Center

Overall contact:
SP Clinical Trial Registry Call Center, Phone: 1-888-772-8734

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").

Official title: A Multicenter, Randomized, Controlled, Double-Blind, Double-Dummy, Two-Arm Study of Posaconazole vs Fluconazole in the Treatment of Coccidioidomycosis

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

Primary outcome: 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.

Secondary outcome: 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

Minimum age: 13 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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.

SP Clinical Trial Registry Call Center, Phone: 1-888-772-8734

Investigational Site 10, Phoenix, Arizona 85008, United States; Terminated

Investigational Site 6, Phoenix, Arizona 85054, United States; Suspended

Investigational Site 12, Scottsdale, Arizona 85258, United States; Suspended

Investigational Site 11, Fresno, California 93720, United States; Suspended

Investigational Site 14, Los Angeles, California 90033, United States; Suspended

Investigational Site 17, Orange, California 92868, United States; Recruiting

Investigational Site 16, El Paso, Texas 79905, United States; Terminated

Starting date: May 2007
Ending date: May 2009
Last updated: May 28, 2008