Clinical trial NCT00423267: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Coccidioidomycosis
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2007-01-18
Enrollment: 16
Sex: ALL
Minimum age (years): 13
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Number of Participants With Treatment-related Treatment-emergent Adverse Events (TRAEs) That Occurred With Posaconazole (POS) or Fluconazole (FLU) in Period A
timeFrame: 12 months
measure: Number of Participants With Treatment-related Treatment-emergent Adverse Events (TRAEs) That Occurred With Posaconazole (POS) in Period B
timeFrame: 12 months
Secondary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs)That Occurred With POS or FLU in Period A
timeFrame: 12 months
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) That Occurred With POS in Period B
timeFrame: 12 months
measure: Number of Participants With Laboratory Test Abnormalities (at Least a 1 Grade Shift From Baseline) That Occurred With POS or FLU in Period A
timeFrame: 12 months
measure: Number of Participants With Laboratory Abnormalities (at Least a 1 Grade Shift From Baseline) That Occurred With POS in Period B
timeFrame: 12 months
measure: Number of Participant Discontinuations Due to Adverse Events and/or Laboratory Evaluations of Safety in Period A
timeFrame: 12 months
measure: Number of Participant Discontinuations Due to Adverse Events and/or Laboratory Evaluations of Safety in Period B
timeFrame: 12 months
Other outcomes:
Locations:
Study officials:
References: