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

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

Sponsors

Lead Sponsor: Merck Sharp & Dohme Corp.

Source Merck Sharp & Dohme Corp.
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.

Overall Status Completed
Start Date May 2007
Completion Date May 2009
Primary Completion Date May 2009
Phase Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
Number of Participants With Treatment-related Treatment-emergent Adverse Events (TRAEs) That Occurred With Posaconazole (POS) or Fluconazole (FLU) in Period A 12 months
Number of Participants With Treatment-related Treatment-emergent Adverse Events (TRAEs) That Occurred With Posaconazole (POS) in Period B 12 months
Secondary Outcome
Measure Time Frame
Number of Participants With Treatment-emergent Adverse Events (TEAEs)That Occurred With POS or FLU in Period A 12 months
Number of Participants With Treatment-emergent Adverse Events (TEAEs) That Occurred With POS in Period B 12 months
Number of Participants With Laboratory Test Abnormalities (at Least a 1 Grade Shift From Baseline) That Occurred With POS or FLU in Period A 12 months
Number of Participants With Laboratory Abnormalities (at Least a 1 Grade Shift From Baseline) That Occurred With POS in Period B 12 months
Number of Participant Discontinuations Due to Adverse Events and/or Laboratory Evaluations of Safety in Period A 12 months
Number of Participant Discontinuations Due to Adverse Events and/or Laboratory Evaluations of Safety in Period B 12 months
Enrollment 16
Condition
Intervention

Intervention Type: Drug

Intervention Name: Posaconazole

Description: Posaconazole 400 mg orally (PO) (oral suspension 40 mg/mL) administered twice daily with meals or oral nutritional supplements for 12 months

Arm Group Label: Posaconazole

Intervention Type: Drug

Intervention Name: Fluconazole

Description: Fluconazole 400 mg PO (given as two 200-mg oral encapsulated tablets) administered once daily for 12 months

Arm Group Label: Fluconazole

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.

Gender: All

Minimum Age: 13 Years

Maximum Age: N/A

Healthy Volunteers: No

Verification Date

March 2017

Responsible Party

Type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Posaconazole

Type: Experimental

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.

Label: Fluconazole

Type: Active Comparator

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.

Patient Data Yes
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Source: ClinicalTrials.gov