Aspergillosis, Candidiasis, Esophageal, Candidiasis, Invasive
Conditions
Brief summary
The study estimates the safety, efficacy, and pharmacokinetics of caspofungin (MK-0991) in Japanese children and adolescents with documented Candida or Aspergillus infections.
Interventions
DRUGCaspofungin
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Months to 17 Years
Healthy volunteers
No
Inclusion criteria
* Japanese patients in whom a causative fungus is detected before treatment with the study drug or patients with strongly suspected deep-seated fungal infection due to Candida species (spp.) or Aspergillus spp.
Exclusion criteria
* Patients with mycoses other than ones due to Candida spp. or Aspergillus spp. * Patients who will receive other systemic antifungal agents for the first time in screening period
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With an Overall Favorable Response to Therapy | Invasive candidiasis: up to 56 days; aspergillosis: up to 84 days | Invasive candidiasis: favorable overall response required resolved clinical findings and negative culture test for Candida species on follow-up. If Candida species were not observed in the baseline blood culture, favorable overall response required resolved clinical findings and resolved or improved radiographic findings. Aspergillosis: favorable overall response required resolved, improved, or unchanged clinical findings and resolved or improved radiographic findings, or resolved or improved clinical findings and resolved, improved, or stable radiographic findings. |
| Percentage of Participants With One or More Drug-Related Adverse Experiences | Invasive candidiasis: up to 70 days; aspergillosis: up to 98 days | An adverse experience (AE) is defined as any unfavorable or unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug. Any worsening of a preexisting condition which is temporally associated with the use of the study drug is also an AE. A drug-related AE is one judged to be definitely, probably, or possibly related to the study drug. |
Participant flow
Recruitment details
Participants with documented esophageal candidiasis, invasive candidiasis, or aspergillosis and who met all of the additional inclusion and exclusion criteria were to be enrolled in the study
Pre-assignment details
Three participants were initially enrolled but were withdrawn when their suspected fungal infections were not confirmed. These 3 participants did not receive study drug. No participants with esophageal candidiasis were identified for inclusion in the study.
Participants by arm
| Arm | Count |
|---|---|
| Participants With Invasive Candidiasis MK-0991 therapy as a single loading dose of 70 mg/m\^2 intravenously on Day 1 (maximum not to exceed 70 mg), followed by 50 mg/m\^2 as a single once-daily dose on all subsequent days (maximum of 70 mg daily). The minimum and maximum treatment duration was 14 and 56 days, respectively. | 12 |
| Participants With Aspergillosis MK-0991 therapy as a single loading dose of 70 mg/m\^2 intravenously on Day 1 (maximum not to exceed 70 mg), followed by 50 mg/m\^2 as a single once-daily dose on all subsequent days (maximum of 70 mg daily). The minimum and maximum treatment duration was 14 and 84 days, respectively. | 8 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Clinical adverse experience | 2 | 1 | 0 |
| Overall Study | Laboratory adverse experience | 1 | 0 | 0 |
| Overall Study | Lack of Efficacy | 0 | 2 | 0 |
| Overall Study | Reason unknown | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Participants With Invasive Candidiasis | Participants With Aspergillosis | Total |
|---|---|---|---|
| Age, Continuous | 9.8 Years STANDARD_DEVIATION 5.2 | 9.8 Years STANDARD_DEVIATION 5.2 | 9.8 Years STANDARD_DEVIATION 5 |
| Age, Customized >=12 years and <18 years | 4 Participants | 4 Participants | 8 Participants |
| Age, Customized >=2 years and <12 years | 8 Participants | 3 Participants | 11 Participants |
| Age, Customized >=3 months and <2 years | 0 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Female | 9 Participants | 6 Participants | 15 Participants |
| Sex: Female, Male Male | 3 Participants | 2 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 10 / 12 | 5 / 8 |
| serious Total, serious adverse events | 1 / 12 | 2 / 8 |
Outcome results
Primary
Percentage of Participants With an Overall Favorable Response to Therapy
Invasive candidiasis: favorable overall response required resolved clinical findings and negative culture test for Candida species on follow-up. If Candida species were not observed in the baseline blood culture, favorable overall response required resolved clinical findings and resolved or improved radiographic findings. Aspergillosis: favorable overall response required resolved, improved, or unchanged clinical findings and resolved or improved radiographic findings, or resolved or improved clinical findings and resolved, improved, or stable radiographic findings.
Time frame: Invasive candidiasis: up to 56 days; aspergillosis: up to 84 days
Population: The full analysis set included all enrolled participants who received \>=1 dose of study drug. No participants with esophageal candidiasis were identified for inclusion in the study and assessment for response to therapy. Participants whose overall response assessment was unable to judge were counted as having an unfavorable response.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants With Invasive Candidiasis | Percentage of Participants With an Overall Favorable Response to Therapy | 66.7 Percentage of Participants |
| Participants With Aspergillosis | Percentage of Participants With an Overall Favorable Response to Therapy | 62.5 Percentage of Participants |
Primary
Percentage of Participants With One or More Drug-Related Adverse Experiences
An adverse experience (AE) is defined as any unfavorable or unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug. Any worsening of a preexisting condition which is temporally associated with the use of the study drug is also an AE. A drug-related AE is one judged to be definitely, probably, or possibly related to the study drug.
Time frame: Invasive candidiasis: up to 70 days; aspergillosis: up to 98 days
Population: The full analysis set included all enrolled participants who received \>=1 dose of study drug. No participants with esophageal candidiasis were identified for inclusion in the study and assessment for safety outcomes.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants With Invasive Candidiasis | Percentage of Participants With One or More Drug-Related Adverse Experiences | 58.3 Percentage of Participants |
| Participants With Aspergillosis | Percentage of Participants With One or More Drug-Related Adverse Experiences | 37.5 Percentage of Participants |