Coccidioidomycosis
Conditions
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.
Interventions
DRUGPosaconazole
Posaconazole 400 mg orally (PO) (oral suspension 40 mg/mL) administered twice daily with meals or oral nutritional supplements for 12 months
DRUGFluconazole
Fluconazole 400 mg PO (given as two 200-mg oral encapsulated tablets) administered once daily for 12 months
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
13 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-related Treatment-emergent Adverse Events (TRAEs) That Occurred With Posaconazole (POS) or Fluconazole (FLU) in Period A | 12 months | Treatment-emergent adverse events are defined as new events that occur following subject entry into the study or events that worsen following study entry state. Treatment-related adverse events are defined as new events that occur following subject entry into the study or events that worsen following study entry state and are judged by the investigator to be possibly, probably or definitely related to study medication. |
| Number of Participants With Treatment-related Treatment-emergent Adverse Events (TRAEs) That Occurred With Posaconazole (POS) in Period B | 12 months | Treatment-emergent adverse events are defined as new events that occur following subject entry into the study or events that worsen following study entry state. Treatment-related adverse events are defined as new events that occur following subject entry into the study or events that worsen following study entry state and are judged by the investigator to be possibly, probably or definitely related to study medication. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Severity grading was based on Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0. This is a descriptive terminology which can be utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term. CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE; Grade 2 Moderate AE; Grade 3 Severe AE; Grade 4 Life-threatening or disabling AE; Grade 5 Death related to AE. |
| Number of Participants With Laboratory Abnormalities (at Least a 1 Grade Shift From Baseline) That Occurred With POS in Period B | 12 months | Severity grading was based on Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0. This is a descriptive terminology which can be utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term. CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE; Grade 2 Moderate AE; Grade 3 Severe AE; Grade 4 Life-threatening or disabling AE; Grade 5 Death related to AE. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs)That Occurred With POS or FLU in Period A | 12 months | Treatment-emergent adverse events are defined as new events that occur following subject entry into the study or events that worsen following study entry state. |
| Number of Participant Discontinuations Due to Adverse Events and/or Laboratory Evaluations of Safety 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 Participants With Treatment-emergent Adverse Events (TEAEs) That Occurred With POS in Period B | 12 months | Treatment-emergent adverse events are defined as new events that occur following subject entry into the study or events that worsen following study entry state. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Posaconazole 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. | 9 |
| Fluconazole 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. Participants in this arm were given posaconazole in Period B. | 7 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period A | Administrative | 1 | 0 |
| Period A | Non-compliance with protocol | 1 | 0 |
| Period A | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Posaconazole | Fluconazole | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 0 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 7 Participants | 14 Participants |
| Sex: Female, Male Female | 4 Participants | 2 Participants | 6 Participants |
| Sex: Female, Male Male | 5 Participants | 5 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 8 / 9 | 5 / 7 | 8 / 12 |
| serious Total, serious adverse events | 0 / 9 | 0 / 7 | 1 / 12 |
Outcome results
Primary
Number of Participants With Treatment-related Treatment-emergent Adverse Events (TRAEs) That Occurred With Posaconazole (POS) in Period B
Treatment-emergent adverse events are defined as new events that occur following subject entry into the study or events that worsen following study entry state. Treatment-related adverse events are defined as new events that occur following subject entry into the study or events that worsen following study entry state and are judged by the investigator to be possibly, probably or definitely related to study medication.
Time frame: 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Posaconazole | Number of Participants With Treatment-related Treatment-emergent Adverse Events (TRAEs) That Occurred With Posaconazole (POS) in Period B | 3 Participants |
Primary
Number of Participants With Treatment-related Treatment-emergent Adverse Events (TRAEs) That Occurred With Posaconazole (POS) or Fluconazole (FLU) in Period A
Treatment-emergent adverse events are defined as new events that occur following subject entry into the study or events that worsen following study entry state. Treatment-related adverse events are defined as new events that occur following subject entry into the study or events that worsen following study entry state and are judged by the investigator to be possibly, probably or definitely related to study medication.
Time frame: 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Posaconazole | Number of Participants With Treatment-related Treatment-emergent Adverse Events (TRAEs) That Occurred With Posaconazole (POS) or Fluconazole (FLU) in Period A | 5 Participants |
| Fluconazole | Number of Participants With Treatment-related Treatment-emergent Adverse Events (TRAEs) That Occurred With Posaconazole (POS) or Fluconazole (FLU) in Period A | 3 Participants |
Secondary
Number of Participant Discontinuations Due to Adverse Events and/or Laboratory Evaluations of Safety in Period A
Time frame: 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Posaconazole | Number of Participant Discontinuations Due to Adverse Events and/or Laboratory Evaluations of Safety in Period A | 0 Participants |
| Fluconazole | Number of Participant Discontinuations Due to Adverse Events and/or Laboratory Evaluations of Safety in Period A | 0 Participants |
Secondary
Number of Participant Discontinuations Due to Adverse Events and/or Laboratory Evaluations of Safety in Period B
Time frame: 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Posaconazole | Number of Participant Discontinuations Due to Adverse Events and/or Laboratory Evaluations of Safety in Period B | 0 Participants |
Secondary
Number of Participants With Laboratory Abnormalities (at Least a 1 Grade Shift From Baseline) That Occurred With POS in Period B
Severity grading was based on Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0. This is a descriptive terminology which can be utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term. CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE; Grade 2 Moderate AE; Grade 3 Severe AE; Grade 4 Life-threatening or disabling AE; Grade 5 Death related to AE.
Time frame: 12 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Posaconazole | Number of Participants With Laboratory Abnormalities (at Least a 1 Grade Shift From Baseline) That Occurred With POS in Period B | Hematology | 2 Participants |
| Posaconazole | Number of Participants With Laboratory Abnormalities (at Least a 1 Grade Shift From Baseline) That Occurred With POS in Period B | Liver function tests | 11 Participants |
| Posaconazole | Number of Participants With Laboratory Abnormalities (at Least a 1 Grade Shift From Baseline) That Occurred With POS in Period B | Renal function tests | 1 Participants |
| Posaconazole | Number of Participants With Laboratory Abnormalities (at Least a 1 Grade Shift From Baseline) That Occurred With POS in Period B | Electrolytes | 0 Participants |
Secondary
Number of Participants With Laboratory Test Abnormalities (at Least a 1 Grade Shift From Baseline) That Occurred With POS or FLU in Period A
Severity grading was based on Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0. This is a descriptive terminology which can be utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term. CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE; Grade 2 Moderate AE; Grade 3 Severe AE; Grade 4 Life-threatening or disabling AE; Grade 5 Death related to AE.
Time frame: 12 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Posaconazole | Number of Participants With Laboratory Test Abnormalities (at Least a 1 Grade Shift From Baseline) That Occurred With POS or FLU in Period A | Hematology | 4 Participants |
| Posaconazole | Number of Participants With Laboratory Test Abnormalities (at Least a 1 Grade Shift From Baseline) That Occurred With POS or FLU in Period A | Liver function tests | 4 Participants |
| Posaconazole | Number of Participants With Laboratory Test Abnormalities (at Least a 1 Grade Shift From Baseline) That Occurred With POS or FLU in Period A | Renal function tests | 0 Participants |
| Posaconazole | Number of Participants With Laboratory Test Abnormalities (at Least a 1 Grade Shift From Baseline) That Occurred With POS or FLU in Period A | Electrolytes | 0 Participants |
| Fluconazole | Number of Participants With Laboratory Test Abnormalities (at Least a 1 Grade Shift From Baseline) That Occurred With POS or FLU in Period A | Electrolytes | 2 Participants |
| Fluconazole | Number of Participants With Laboratory Test Abnormalities (at Least a 1 Grade Shift From Baseline) That Occurred With POS or FLU in Period A | Hematology | 1 Participants |
| Fluconazole | Number of Participants With Laboratory Test Abnormalities (at Least a 1 Grade Shift From Baseline) That Occurred With POS or FLU in Period A | Renal function tests | 1 Participants |
| Fluconazole | Number of Participants With Laboratory Test Abnormalities (at Least a 1 Grade Shift From Baseline) That Occurred With POS or FLU in Period A | Liver function tests | 3 Participants |
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs) That Occurred With POS in Period B
Treatment-emergent adverse events are defined as new events that occur following subject entry into the study or events that worsen following study entry state.
Time frame: 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Posaconazole | Number of Participants With Treatment-emergent Adverse Events (TEAEs) That Occurred With POS in Period B | 8 Participants |
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs)That Occurred With POS or FLU in Period A
Treatment-emergent adverse events are defined as new events that occur following subject entry into the study or events that worsen following study entry state.
Time frame: 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Posaconazole | Number of Participants With Treatment-emergent Adverse Events (TEAEs)That Occurred With POS or FLU in Period A | 8 Participants |
| Fluconazole | Number of Participants With Treatment-emergent Adverse Events (TEAEs)That Occurred With POS or FLU in Period A | 5 Participants |