Aspergillosis
Conditions
Brief summary
The primary objective of this study is to assess and compare the safety of posaconazole with voriconazole in Japanese participants with aspergillosis.
Interventions
DRUGPosaconazole
300 mg posaconazole twice on Day 1, either by oral tablet or IV solution; followed by 300 mg once daily for up to 84 days
DRUGVoriconazole
300 mg voriconazole oral tablet (or 6 mg/kg IV solution) twice on Day 1, followed by 200 mg oral tablet (or 4 mg/kg IV solution) twice daily for up to 84 days
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Body weight \>=45 kg * Can be treated by taking tablet orally or intravenous (IV) formulation via central vein * Female has a negative pregnancy test * Female of non-childbearing potential; or if of childbearing potential, agrees to use proper combination of barrier method of birth control * Met screening criteria for either Invasive aspergillosis, chronic pulmonary aspergillosis, zygomycosis or fusariosis.
Exclusion criteria
* Has a fungal infection other than Aspergillus any species (spp.) Zygomycetes (including Mucor spp.) and Fusarium spp. infection * Has allergic bronchopulmonary aspergillosis, allergic sinusitis of aspergillosis, or aspergillosis of the eye * Has long-term inactive aspergilloma not expected to respond to investigational product * Is not expected to survive study duration * Has an underlying disease, complication and systemic condition which makes it difficult to evaluate effect of study drug * Has received, or continues to receive any systemic antifungal therapy, and cannot discontinue this treatment; but if fungal infection does not improve, can switch to study drug * Is expected to need prohibited medications * Has received posaconazole, has received voriconazole for this infection in the past and has deep-seated fungal infection that has not responded to this treatment, has intolerance for azole antifungal treatments, or is receiving antifungal combination therapy for chronic pulmonary aspergillosis * Has known hypersensitivity to any medication * Has history of either Torsade de Pointes, myocardial infarction within previous 90 days, has congenital or acquired long QT interval syndrome, or unstable cardiac arrhythmia * Has significant liver dysfunction * Has liver cirrhosis or cholestasis * Has renal insufficiency * Has a known hereditary problem of either galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption * Has acute symptomatic pancreatitis within 6 months of study entry or chronic pancreatitis * Has an active skin lesion consistent with squamous cell carcinoma or melanoma, or within prior 5 years a history of malignant melanoma * Has known or suspected Gilbert's disease * Female is pregnant, or nursing, or intends to become pregnant within 14 days after end of study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With an Adverse Event | Up to approximately Day 98 | An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol specified procedure, whether or not considered related to the medicinal product or protocol specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of the Sponsor's product is also an AE. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Successful Overall Response for Invasive Aspergillosis in Cohort 2 at Day 42 | Day 42 | Successful treatment (or successful overall response) is defined as complete response and partial response to treatment assessed by the clinical adjudication committee (CAC). The 95% confidence interval (CI) is based on the Clopper-Pearson exact method. |
| Percentage of Participants With Successful Overall Response for Invasive Aspergillosis in Cohort 2 at Day 84 | Day 84 | Successful treatment (or successful overall response) is defined as complete response and partial response to treatment assessed by CAC. The 95% CI is based on the Clopper-Pearson exact method. |
| Percentage of Participants With Successful Overall Response for Chronic Pulmonary Aspergillosis in Cohort 2 at Day 84 | Day 84 | Successful treatment (or successful overall response) is defined as favorable response to treatment assessed by CAC. The 95% CI is based on the Clopper-Pearson exact method. |
| Percentage of Participants With Successful Overall Response for Invasive Aspergillosis and Chronic Pulmonary Aspergillosis in Cohort 2 at End of Trial (Day 84) | Day 84 | Successful treatment (or successful overall response) for invasive aspergillosis is defined as complete response and partial response to treatment assessed by CAC. Successful treatment (or successful overall response) for chronic pulmonary aspergillosis is defined as favorable response to treatment.The 95% CI is based on the Clopper-Pearson exact method. |
| Percentage of Participants With Successful Overall Response for Zygomycosis in Cohort 2 at Day 42 | Day 42 | Zygomycosis is an infection caused by zygomycete fungi. Successful treatment (or successful overall response) is defined as complete response and partial response to treatment assessed by CAC. The 95% CI is based on the Clopper-Pearson exact method. |
| Percentage of Participants With Successful Overall Response for Zygomycosis in Cohort 2 at Day 84 | Day 84 | Zygomycosis is an infection caused by zygomycete fungi. Successful treatment (or successful overall response) is defined as complete response and partial response to treatment assessed by CAC. The 95% CI is based on the Clopper-Pearson exact method. |
| Percentage of Participants With Successful Overall Response for Invasive Aspergillosis in Cohort 2 at Day 42 as Assessed by the Clinical Investigator | Day 42 | Successful treatment (or successful overall response) for invasive aspergillosis is defined as complete response and partial response to treatment assessed by the clinical investigator.The 95% CI is based on the Clopper-Pearson exact method. |
| Percentage of Participants With Successful Overall Response for Chronic Pulmonary Aspergillosis in Cohort 2 at Day 84 as Assessed by the Clinical Investigator | Day 84 | Successful treatment (or successful overall response) for chronic pulmonary aspergillosis is defined as favorable response to treatment assessed by the clinical investigator.The 95% CI is based on the Clopper-Pearson exact method. |
| Percentage of Participants With Invasive Aspergillosis With Clinical Response of Resolution or Improvement in Cohort 2 at Day 42 | Day 42 | A clinical response of resolution is defined as resolution of attributable signs and symptoms of disease, and a clinical response of improvement is defined as improvement of attributable signs and symptoms of disease as assessed by the CAC. |
| Percentage of Participants With Successful Overall Response for Chronic Pulmonary Aspergillosis in Cohort 2 at Day 42 | Day 42 | Successful treatment (or successful overall response) is defined as favorable response to treatment assessed by CAC. The 95% CI is based on the Clopper-Pearson exact method. |
| Percentage of Participants With Invasive Aspergillosis With Radiological Response of Resolution or Improvement in Cohort 2 at Day 42 | Day 42 | A radiological response of resolution is defined as resolution of radiological lesions, and a radiological response of improvement is defined as major reduction in size of radiological lesions as assessed by the CAC. |
| Percentage of Participants With Invasive Aspergillosis With Radiological Response of Resolution or Improvement in Cohort 2 at Day 84 | Day 84 | A radiological response of resolution is defined as resolution of radiological lesions, and a radiological response of improvement is defined as major reduction in size of radiological lesions as assessed by the CAC. |
| Percentage of Participants With Invasive Aspergillosis With Mycological Response of Eradication in Cohort 2 at Day 42 | Day 42 | A mycological response of eradication is defined as fungus detected from culture or microscopy at the screening is eradicated at the time of evaluation (including presumed eradication), as assessed by the CAC. |
| Percentage of Participants With Chronic Pulmonary Aspergillosis With Clinical Response of Resolution in Cohort 2 at Day 42 | Day 42 | A clinical response of resolution is defined as resolution of attributable signs and symptoms of disease, as assessed by the CAC. |
| Percentage of Participants With Chronic Pulmonary Aspergillosis With Clinical Response of Resolution in Cohort 2 at Day 84 | Day 84 | A clinical response of resolution is defined as resolution of attributable signs and symptoms of disease, as assessed by the CAC. |
| Percentage of Participants With Chronic Pulmonary Aspergillosis With Radiological Response of Resolution in Cohort 2 at Day 42 | Day 42 | A radiological response of resolution is defined as resolution of radiological lesions, as assessed by the CAC. |
| Percentage of Participants With Chronic Pulmonary Aspergillosis With Mycological Response of Eradication in Cohort 2 at Day 42 | Day 42 | A mycological response of eradication is defined as fungus detected from culture or microscopy at the screening is eradicated at the time of evaluation (including presumed eradication), as assessed by the CAC. |
| Percentage of Participants With Chronic Pulmonary Aspergillosis With Mycological Response of Eradication in Cohort 2 at Day 84 | Day 84 | A mycological response of eradication is defined as fungus detected from culture or microscopy at the screening is eradicated at the time of evaluation (including presumed eradication), as assessed by the CAC. |
| Percentage of Participants With Invasive Aspergillosis With Clinical Response of Resolution or Improvement in Cohort 2 at Day 84 | Day 84 | A clinical response of resolution is defined as resolution of attributable signs and symptoms of disease, and a clinical response of improvement is defined as improvement of attributable signs and symptoms of disease as assessed by the CAC. |
Participant flow
Recruitment details
This study was conducted in male and female Japanese participants with deep-seated fungal infection.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: Posaconazole Participants with chronic pulmonary aspergillosis received 300 mg posaconazole oral tablet (or 300 mg intravenous (IV) solution) twice on Day 1, followed by 300 mg oral tablet or IV solution once daily for up to 84 days | 15 |
| Cohort 1: Voriconazole Participants with chronic pulmonary aspergillosis received 300 mg voriconazole oral tablet (or 6 mg/kg IV solution) twice on Day 1, followed by 200 mg oral tablet (or 4 mg/kg IV solution) twice daily for up to 84 days | 7 |
| Cohort 2: Posaconazole Participants from cohort 2 with invasive aspergillosis and chronic pulmonary aspergillosis received 300 mg posaconazole oral tablet (or 300 mg IV solution) twice on Day 1, followed by 300 mg oral tablet or IV solution once daily for up to 84 days | 57 |
| Cohort 2: Voriconazole Participants from cohort 2 with invasive aspergillosis and chronic pulmonary aspergillosis received 300 mg voriconazole oral tablet (or 6 mg/kg IV solution) twice on Day 1, followed by 200 mg oral tablet (or 4 mg/kg IV solution) twice daily for up to 84 days | 27 |
| Total | 106 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 7 | 0 | 18 | 3 |
| Overall Study | Lack of Efficacy | 0 | 1 | 3 | 2 |
| Overall Study | Not Treated | 0 | 0 | 1 | 0 |
| Overall Study | Physician Decision | 1 | 0 | 5 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 0 | 2 | 1 |
Baseline characteristics
| Characteristic | Cohort 1: Posaconazole | Total | Cohort 2: Voriconazole | Cohort 2: Posaconazole | Cohort 1: Voriconazole |
|---|---|---|---|---|---|
| Age, Continuous | 64.3 Years STANDARD_DEVIATION 9.5 | 63.8 Years STANDARD_DEVIATION 12.4 | 58.2 Years STANDARD_DEVIATION 13.9 | 65.6 Years STANDARD_DEVIATION 12.3 | 69.9 Years STANDARD_DEVIATION 4.5 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 15 Participants | 106 Participants | 27 Participants | 57 Participants | 7 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 3 Participants | 11 Participants | 2 Participants | 3 Participants | 3 Participants |
| Sex: Female, Male Male | 12 Participants | 95 Participants | 25 Participants | 54 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 15 | 1 / 7 | 6 / 62 | 0 / 31 |
| other Total, other adverse events | 15 / 15 | 6 / 7 | 58 / 62 | 31 / 31 |
| serious Total, serious adverse events | 3 / 15 | 2 / 7 | 28 / 62 | 3 / 31 |
Outcome results
Primary
Number of Participants With an Adverse Event
An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol specified procedure, whether or not considered related to the medicinal product or protocol specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of the Sponsor's product is also an AE.
Time frame: Up to approximately Day 98
Population: Cohort 1: All randomized participants with chronic pulmonary aspergillosis who received at least one dose of study treatment. Cohort 2: All randomized participants with invasive aspergillosis and chronic pulmonary aspergillosis who received at least one dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: Posaconazole | Number of Participants With an Adverse Event | 15 Participants |
| Cohort 1: Voriconazole | Number of Participants With an Adverse Event | 6 Participants |
| Cohort 2: Posaconazole | Number of Participants With an Adverse Event | 57 Participants |
| Cohort 2: Voriconazole | Number of Participants With an Adverse Event | 27 Participants |
Secondary
Percentage of Participants With Chronic Pulmonary Aspergillosis With Clinical Response of Resolution in Cohort 2 at Day 42
A clinical response of resolution is defined as resolution of attributable signs and symptoms of disease, as assessed by the CAC.
Time frame: Day 42
Population: Participants in cohort 2 diagnosed by CAC with proven or probable chronic pulmonary aspergillosis; who received at least one dose of study treatment; and had a baseline observation for the analysis endpoint. Participants in cohort 1 were not analyzed for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 2: Posaconazole | Percentage of Participants With Chronic Pulmonary Aspergillosis With Clinical Response of Resolution in Cohort 2 at Day 42 | 43.8 Percentage of participants |
| Cohort 2: Voriconazole | Percentage of Participants With Chronic Pulmonary Aspergillosis With Clinical Response of Resolution in Cohort 2 at Day 42 | 73.9 Percentage of participants |
Secondary
Percentage of Participants With Chronic Pulmonary Aspergillosis With Clinical Response of Resolution in Cohort 2 at Day 84
A clinical response of resolution is defined as resolution of attributable signs and symptoms of disease, as assessed by the CAC.
Time frame: Day 84
Population: Participants in cohort 2 diagnosed by CAC with proven or probable chronic pulmonary aspergillosis; who received at least one dose of study treatment; and had a baseline observation for the analysis endpoint. Participants in cohort 1 were not analyzed for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 2: Posaconazole | Percentage of Participants With Chronic Pulmonary Aspergillosis With Clinical Response of Resolution in Cohort 2 at Day 84 | 45.8 Percentage of participants |
| Cohort 2: Voriconazole | Percentage of Participants With Chronic Pulmonary Aspergillosis With Clinical Response of Resolution in Cohort 2 at Day 84 | 82.6 Percentage of participants |
Secondary
Percentage of Participants With Chronic Pulmonary Aspergillosis With Mycological Response of Eradication in Cohort 2 at Day 42
A mycological response of eradication is defined as fungus detected from culture or microscopy at the screening is eradicated at the time of evaluation (including presumed eradication), as assessed by the CAC.
Time frame: Day 42
Population: Participants in cohort 2 diagnosed by CAC with proven or probable chronic pulmonary aspergillosis; who received at least one dose of study treatment; and had a baseline observation for the analysis endpoint. Participants in cohort 1 were not analyzed for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 2: Posaconazole | Percentage of Participants With Chronic Pulmonary Aspergillosis With Mycological Response of Eradication in Cohort 2 at Day 42 | 33.3 Percentage of participants |
| Cohort 2: Voriconazole | Percentage of Participants With Chronic Pulmonary Aspergillosis With Mycological Response of Eradication in Cohort 2 at Day 42 | 21.7 Percentage of participants |
Secondary
Percentage of Participants With Chronic Pulmonary Aspergillosis With Mycological Response of Eradication in Cohort 2 at Day 84
A mycological response of eradication is defined as fungus detected from culture or microscopy at the screening is eradicated at the time of evaluation (including presumed eradication), as assessed by the CAC.
Time frame: Day 84
Population: Participants in cohort 2 diagnosed by CAC with proven or probable chronic pulmonary aspergillosis; who received at least one dose of study treatment; and had a baseline observation for the analysis endpoint. Participants in cohort 1 were not analyzed for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 2: Posaconazole | Percentage of Participants With Chronic Pulmonary Aspergillosis With Mycological Response of Eradication in Cohort 2 at Day 84 | 35.4 Percentage of participants |
| Cohort 2: Voriconazole | Percentage of Participants With Chronic Pulmonary Aspergillosis With Mycological Response of Eradication in Cohort 2 at Day 84 | 21.7 Percentage of participants |
Secondary
Percentage of Participants With Chronic Pulmonary Aspergillosis With Radiological Response of Resolution in Cohort 2 at Day 42
A radiological response of resolution is defined as resolution of radiological lesions, as assessed by the CAC.
Time frame: Day 42
Population: Participants in cohort 2 diagnosed by CAC with proven or probable chronic pulmonary aspergillosis; who received at least one dose of study treatment; and had a baseline observation for the analysis endpoint. Participants in cohort 1 were not analyzed for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 2: Posaconazole | Percentage of Participants With Chronic Pulmonary Aspergillosis With Radiological Response of Resolution in Cohort 2 at Day 42 | 58.3 Percentage of participants |
| Cohort 2: Voriconazole | Percentage of Participants With Chronic Pulmonary Aspergillosis With Radiological Response of Resolution in Cohort 2 at Day 42 | 87.0 Percentage of participants |
Secondary
Percentage of Participants With Invasive Aspergillosis With Clinical Response of Resolution or Improvement in Cohort 2 at Day 42
A clinical response of resolution is defined as resolution of attributable signs and symptoms of disease, and a clinical response of improvement is defined as improvement of attributable signs and symptoms of disease as assessed by the CAC.
Time frame: Day 42
Population: Participants in cohort 2 diagnosed by CAC with proven or probable invasive aspergillosis; who received at least one dose of study treatment; and had a baseline observation for the analysis endpoint. Participants in cohort 1 were not analyzed for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 2: Posaconazole | Percentage of Participants With Invasive Aspergillosis With Clinical Response of Resolution or Improvement in Cohort 2 at Day 42 | Resolution | 60.0 Percentage of participants |
| Cohort 2: Posaconazole | Percentage of Participants With Invasive Aspergillosis With Clinical Response of Resolution or Improvement in Cohort 2 at Day 42 | Improvement | 20.0 Percentage of participants |
| Cohort 2: Voriconazole | Percentage of Participants With Invasive Aspergillosis With Clinical Response of Resolution or Improvement in Cohort 2 at Day 42 | Resolution | 0 Percentage of participants |
| Cohort 2: Voriconazole | Percentage of Participants With Invasive Aspergillosis With Clinical Response of Resolution or Improvement in Cohort 2 at Day 42 | Improvement | 66.7 Percentage of participants |
Secondary
Percentage of Participants With Invasive Aspergillosis With Clinical Response of Resolution or Improvement in Cohort 2 at Day 84
A clinical response of resolution is defined as resolution of attributable signs and symptoms of disease, and a clinical response of improvement is defined as improvement of attributable signs and symptoms of disease as assessed by the CAC.
Time frame: Day 84
Population: Participants in cohort 2 diagnosed by CAC with proven or probable invasive aspergillosis; who received at least one dose of study treatment; and had a baseline observation for the analysis endpoint. Participants in cohort 1 were not analyzed for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 2: Posaconazole | Percentage of Participants With Invasive Aspergillosis With Clinical Response of Resolution or Improvement in Cohort 2 at Day 84 | Resolution | 60.0 Percentage of participants |
| Cohort 2: Posaconazole | Percentage of Participants With Invasive Aspergillosis With Clinical Response of Resolution or Improvement in Cohort 2 at Day 84 | Improvement | 20.0 Percentage of participants |
| Cohort 2: Voriconazole | Percentage of Participants With Invasive Aspergillosis With Clinical Response of Resolution or Improvement in Cohort 2 at Day 84 | Resolution | 33.3 Percentage of participants |
| Cohort 2: Voriconazole | Percentage of Participants With Invasive Aspergillosis With Clinical Response of Resolution or Improvement in Cohort 2 at Day 84 | Improvement | 33.3 Percentage of participants |
Secondary
Percentage of Participants With Invasive Aspergillosis With Mycological Response of Eradication in Cohort 2 at Day 42
A mycological response of eradication is defined as fungus detected from culture or microscopy at the screening is eradicated at the time of evaluation (including presumed eradication), as assessed by the CAC.
Time frame: Day 42
Population: Participants in cohort 2 diagnosed by CAC with proven or probable invasive aspergillosis; who received at least one dose of study treatment; and had a baseline observation for the analysis endpoint. Participants in cohort 1 were not analyzed for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 2: Posaconazole | Percentage of Participants With Invasive Aspergillosis With Mycological Response of Eradication in Cohort 2 at Day 42 | 20.0 Percentage of participants |
| Cohort 2: Voriconazole | Percentage of Participants With Invasive Aspergillosis With Mycological Response of Eradication in Cohort 2 at Day 42 | 0 Percentage of participants |
Secondary
Percentage of Participants With Invasive Aspergillosis With Radiological Response of Resolution or Improvement in Cohort 2 at Day 42
A radiological response of resolution is defined as resolution of radiological lesions, and a radiological response of improvement is defined as major reduction in size of radiological lesions as assessed by the CAC.
Time frame: Day 42
Population: Participants in cohort 2 diagnosed by CAC with proven or probable invasive aspergillosis; who received at least one dose of study treatment; and had a baseline observation for the analysis endpoint. Participants in cohort 1 were not analyzed for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 2: Posaconazole | Percentage of Participants With Invasive Aspergillosis With Radiological Response of Resolution or Improvement in Cohort 2 at Day 42 | Resolution | 0 Percentage of participants |
| Cohort 2: Posaconazole | Percentage of Participants With Invasive Aspergillosis With Radiological Response of Resolution or Improvement in Cohort 2 at Day 42 | Improvement | 40.0 Percentage of participants |
| Cohort 2: Voriconazole | Percentage of Participants With Invasive Aspergillosis With Radiological Response of Resolution or Improvement in Cohort 2 at Day 42 | Resolution | 0 Percentage of participants |
| Cohort 2: Voriconazole | Percentage of Participants With Invasive Aspergillosis With Radiological Response of Resolution or Improvement in Cohort 2 at Day 42 | Improvement | 100 Percentage of participants |
Secondary
Percentage of Participants With Invasive Aspergillosis With Radiological Response of Resolution or Improvement in Cohort 2 at Day 84
A radiological response of resolution is defined as resolution of radiological lesions, and a radiological response of improvement is defined as major reduction in size of radiological lesions as assessed by the CAC.
Time frame: Day 84
Population: Participants in cohort 2 diagnosed by CAC with proven or probable invasive aspergillosis; who received at least one dose of study treatment; and had a baseline observation for the analysis endpoint. Participants in cohort 1 were not analyzed for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 2: Posaconazole | Percentage of Participants With Invasive Aspergillosis With Radiological Response of Resolution or Improvement in Cohort 2 at Day 84 | Resolution | 0 Percentage of participants |
| Cohort 2: Posaconazole | Percentage of Participants With Invasive Aspergillosis With Radiological Response of Resolution or Improvement in Cohort 2 at Day 84 | Improvement | 60.0 Percentage of participants |
| Cohort 2: Voriconazole | Percentage of Participants With Invasive Aspergillosis With Radiological Response of Resolution or Improvement in Cohort 2 at Day 84 | Resolution | 0 Percentage of participants |
| Cohort 2: Voriconazole | Percentage of Participants With Invasive Aspergillosis With Radiological Response of Resolution or Improvement in Cohort 2 at Day 84 | Improvement | 100 Percentage of participants |
Secondary
Percentage of Participants With Successful Overall Response for Chronic Pulmonary Aspergillosis in Cohort 2 at Day 42
Successful treatment (or successful overall response) is defined as favorable response to treatment assessed by CAC. The 95% CI is based on the Clopper-Pearson exact method.
Time frame: Day 42
Population: Participants in cohort 2 diagnosed by CAC with proven or probable chronic pulmonary aspergillosis; who received at least one dose of study treatment; and had a baseline observation for the analysis endpoint. Participants in cohort 1 were not analyzed for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 2: Posaconazole | Percentage of Participants With Successful Overall Response for Chronic Pulmonary Aspergillosis in Cohort 2 at Day 42 | 56.3 Percentage of participants |
| Cohort 2: Voriconazole | Percentage of Participants With Successful Overall Response for Chronic Pulmonary Aspergillosis in Cohort 2 at Day 42 | 87.0 Percentage of participants |
Secondary
Percentage of Participants With Successful Overall Response for Chronic Pulmonary Aspergillosis in Cohort 2 at Day 84
Successful treatment (or successful overall response) is defined as favorable response to treatment assessed by CAC. The 95% CI is based on the Clopper-Pearson exact method.
Time frame: Day 84
Population: Participants in cohort 2 diagnosed by CAC with proven or probable chronic pulmonary aspergillosis; who received at least one dose of study treatment; and had a baseline observation for the analysis endpoint. Participants in cohort 1 were not analyzed for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 2: Posaconazole | Percentage of Participants With Successful Overall Response for Chronic Pulmonary Aspergillosis in Cohort 2 at Day 84 | 58.3 Percentage of participants |
| Cohort 2: Voriconazole | Percentage of Participants With Successful Overall Response for Chronic Pulmonary Aspergillosis in Cohort 2 at Day 84 | 87.0 Percentage of participants |
Secondary
Percentage of Participants With Successful Overall Response for Chronic Pulmonary Aspergillosis in Cohort 2 at Day 84 as Assessed by the Clinical Investigator
Successful treatment (or successful overall response) for chronic pulmonary aspergillosis is defined as favorable response to treatment assessed by the clinical investigator.The 95% CI is based on the Clopper-Pearson exact method.
Time frame: Day 84
Population: Participants in cohort 2 diagnosed by CAC with proven or probable chronic pulmonary aspergillosis; who received at least one dose of study treatment; and had a baseline observation for the analysis endpoint. Participants in cohort 1 were not analyzed for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 2: Posaconazole | Percentage of Participants With Successful Overall Response for Chronic Pulmonary Aspergillosis in Cohort 2 at Day 84 as Assessed by the Clinical Investigator | 60.4 Percentage of participants |
| Cohort 2: Voriconazole | Percentage of Participants With Successful Overall Response for Chronic Pulmonary Aspergillosis in Cohort 2 at Day 84 as Assessed by the Clinical Investigator | 78.3 Percentage of participants |
Secondary
Percentage of Participants With Successful Overall Response for Invasive Aspergillosis and Chronic Pulmonary Aspergillosis in Cohort 2 at End of Trial (Day 84)
Successful treatment (or successful overall response) for invasive aspergillosis is defined as complete response and partial response to treatment assessed by CAC. Successful treatment (or successful overall response) for chronic pulmonary aspergillosis is defined as favorable response to treatment.The 95% CI is based on the Clopper-Pearson exact method.
Time frame: Day 84
Population: Participants in cohort 2 diagnosed by CAC with proven or probable invasive aspergillosis or chronic pulmonary aspergillosis; who received at least one dose of study treatment; and had a baseline observation for the analysis endpoint. Participants in cohort 1 were not analyzed for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 2: Posaconazole | Percentage of Participants With Successful Overall Response for Invasive Aspergillosis and Chronic Pulmonary Aspergillosis in Cohort 2 at End of Trial (Day 84) | 58.5 Percentage of participants |
| Cohort 2: Voriconazole | Percentage of Participants With Successful Overall Response for Invasive Aspergillosis and Chronic Pulmonary Aspergillosis in Cohort 2 at End of Trial (Day 84) | 88.5 Percentage of participants |
Secondary
Percentage of Participants With Successful Overall Response for Invasive Aspergillosis in Cohort 2 at Day 42
Successful treatment (or successful overall response) is defined as complete response and partial response to treatment assessed by the clinical adjudication committee (CAC). The 95% confidence interval (CI) is based on the Clopper-Pearson exact method.
Time frame: Day 42
Population: Participants in cohort 2 diagnosed by CAC with proven or probable invasive aspergillosis; who received at least one dose of study treatment; and had a baseline observation for the analysis endpoint. Participants in cohort 1 were not analyzed for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 2: Posaconazole | Percentage of Participants With Successful Overall Response for Invasive Aspergillosis in Cohort 2 at Day 42 | 40.0 Percentage of participants |
| Cohort 2: Voriconazole | Percentage of Participants With Successful Overall Response for Invasive Aspergillosis in Cohort 2 at Day 42 | 100 Percentage of participants |
Secondary
Percentage of Participants With Successful Overall Response for Invasive Aspergillosis in Cohort 2 at Day 42 as Assessed by the Clinical Investigator
Successful treatment (or successful overall response) for invasive aspergillosis is defined as complete response and partial response to treatment assessed by the clinical investigator.The 95% CI is based on the Clopper-Pearson exact method.
Time frame: Day 42
Population: Participants in cohort 2 diagnosed by CAC with proven or probable invasive aspergillosis; who received at least one dose of study treatment; and had a baseline observation for the analysis endpoint. Participants in cohort 1 were not analyzed for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 2: Posaconazole | Percentage of Participants With Successful Overall Response for Invasive Aspergillosis in Cohort 2 at Day 42 as Assessed by the Clinical Investigator | 80.0 Percentage of participants |
| Cohort 2: Voriconazole | Percentage of Participants With Successful Overall Response for Invasive Aspergillosis in Cohort 2 at Day 42 as Assessed by the Clinical Investigator | 66.7 Percentage of participants |
Secondary
Percentage of Participants With Successful Overall Response for Invasive Aspergillosis in Cohort 2 at Day 84
Successful treatment (or successful overall response) is defined as complete response and partial response to treatment assessed by CAC. The 95% CI is based on the Clopper-Pearson exact method.
Time frame: Day 84
Population: Participants in cohort 2 diagnosed by CAC with proven or probable invasive aspergillosis; who received at least one dose of study treatment; and had a baseline observation for the analysis endpoint. Participants in cohort 1 were not analyzed for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 2: Posaconazole | Percentage of Participants With Successful Overall Response for Invasive Aspergillosis in Cohort 2 at Day 84 | 60.0 Percentage of participants |
| Cohort 2: Voriconazole | Percentage of Participants With Successful Overall Response for Invasive Aspergillosis in Cohort 2 at Day 84 | 100 Percentage of participants |
Secondary
Percentage of Participants With Successful Overall Response for Zygomycosis in Cohort 2 at Day 42
Zygomycosis is an infection caused by zygomycete fungi. Successful treatment (or successful overall response) is defined as complete response and partial response to treatment assessed by CAC. The 95% CI is based on the Clopper-Pearson exact method.
Time frame: Day 42
Population: Participants in cohort 2, posaconazole treatment only, diagnosed by CAC with proven or probable zygomycosis; who received at least one dose of study treatment; and had a baseline observation for the analysis endpoint. Participants in cohort 1, and cohort 2 voriconazole treatment were not analyzed for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 2: Posaconazole | Percentage of Participants With Successful Overall Response for Zygomycosis in Cohort 2 at Day 42 | 66.7 Percentage of participants |
Secondary
Percentage of Participants With Successful Overall Response for Zygomycosis in Cohort 2 at Day 84
Zygomycosis is an infection caused by zygomycete fungi. Successful treatment (or successful overall response) is defined as complete response and partial response to treatment assessed by CAC. The 95% CI is based on the Clopper-Pearson exact method.
Time frame: Day 84
Population: Participants in cohort 2, posaconazole treatment only, diagnosed by CAC with proven or probable zygomycosis; who received at least one dose of study treatment; and had a baseline observation for the analysis endpoint. Participants in cohort 1, and cohort 2 voriconazole treatment were not analyzed for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 2: Posaconazole | Percentage of Participants With Successful Overall Response for Zygomycosis in Cohort 2 at Day 84 | 100 Percentage of participants |