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

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 3

Conditions: Coccidioidomycosis

Treatments: Drug: Posaconazole; Drug: Fluconazole

Study type: Interventional

Funder types: Industry

Identifiers

NCT00423267

P04558

Details and patient eligibility

About

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.

Enrollment: 16 patients

Sex: All

Ages: 13+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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16 participants in 2 patient groups

Posaconazole

Experimental group

Description:

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.

Treatment:

Drug: Posaconazole

Fluconazole

Active Comparator group

Description:

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.

Treatment:

Drug: Fluconazole