A Study of Caspofungin (MK-0991) in Japanese Children and Adolescents With Documented Candida or Aspergillus Infections (MK-0991-074)
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 2 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Participants with Esophageal Candidiasis Candida infection is strongly suspected based on clinical symptoms and the participant's clinical course, white moss (plaque) is observed on the esophageal mucosa, and therapy via intravenous infusion is judged to be suitable for the present episode of esophageal 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 7 and 28 days, respectively. |
Drug: Caspofungin
Other Names:
|
Experimental: Participants with Invasive Candidiasis Candida infection is strongly suspected based on the presence of refractory fever not responding to an antibiotic agent, or clinical symptoms at the site of disease, or the participant's clinical course. In addition, at least 1 of the following criteria must be met: 1) Candida infection is strongly suspected based on radiographic imaging findings and positive serological test for fungus, 2) yeast is observed by direct microscopy or histopathological test of tissue biopsied from the site of disease, or 3) Candida species are observed by culture test of specimens sampled from the site of disease. 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. |
Drug: Caspofungin
Other Names:
|
Experimental: Participants with Aspergillosis Aspergillus infection is strongly suspected based on clinical symptoms and the participant's clinical course, and characteristic radiographic imaging findings are observed. In addition, at least 1 of the following criteria must be met: 1) risk factors predisposing to an Aspergillus infection, 2) positive serological test for Aspergillus, 3) acute-branching mold with separated hyphae are observed by direct microscopy or histopathological test, or 4) Aspergillus species are observed by culture test. 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. |
Drug: Caspofungin
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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.
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Merck Sharp & Dohme LLC
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 0991-074
- 132240
Study Results
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 Detail | 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. |
Arm/Group Title | Participants With Invasive Candidiasis | Participants With Aspergillosis | Participants With Esophageal Candidiasis |
---|---|---|---|
Arm/Group Description | 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. | 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. | 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 7 and 28 days, respectively. |
Period Title: Overall Study | |||
STARTED | 12 | 8 | 0 |
COMPLETED | 9 | 4 | 0 |
NOT COMPLETED | 3 | 4 | 0 |
Baseline Characteristics
Arm/Group Title | Participants With Invasive Candidiasis | Participants With Aspergillosis | Total |
---|---|---|---|
Arm/Group Description | 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. | 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. | Total of all reporting groups |
Overall Participants | 12 | 8 | 20 |
Age (Years) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [Years] |
9.8
(5.2)
|
9.8
(5.2)
|
9.8
(5.0)
|
Age, Customized (Number) [Number] | |||
>=3 months and <2 years |
0
0%
|
1
12.5%
|
1
5%
|
>=2 years and <12 years |
8
66.7%
|
3
37.5%
|
11
55%
|
>=12 years and <18 years |
4
33.3%
|
4
50%
|
8
40%
|
Sex: Female, Male (Count of Participants) | |||
Female |
9
75%
|
6
75%
|
15
75%
|
Male |
3
25%
|
2
25%
|
5
25%
|
Outcome Measures
Title | Percentage of Participants With an Overall Favorable Response to Therapy |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Participants With Invasive Candidiasis | Participants With Aspergillosis |
---|---|---|
Arm/Group Description | 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 | 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 |
Measure Participants | 12 | 8 |
Number [Percentage of Participants] |
66.7
555.8%
|
62.5
781.3%
|
Title | Percentage of Participants With One or More Drug-Related Adverse Experiences |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Participants With Invasive Candidiasis | Participants With Aspergillosis |
---|---|---|
Arm/Group Description | 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 | 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 |
Measure Participants | 12 | 8 |
Number [Percentage of Participants] |
58.3
485.8%
|
37.5
468.8%
|
Adverse Events
Time Frame | Invasive candidiasis: up to 56 days; aspergillosis: up to 84 days | |||
---|---|---|---|---|
Adverse Event Reporting Description | No participants with esophageal candidiasis were identified for inclusion in the study and assessment for adverse events | |||
Arm/Group Title | Participants With Invasive Candidiasis | Participants With Aspergillosis | ||
Arm/Group Description | 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. | 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. | ||
All Cause Mortality |
||||
Participants With Invasive Candidiasis | Participants With Aspergillosis | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
Participants With Invasive Candidiasis | Participants With Aspergillosis | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 1/12 (8.3%) | 2/8 (25%) | ||
Infections and infestations | ||||
Pneumonia | 0/12 (0%) | 0 | 1/8 (12.5%) | 1 |
Sepsis | 1/12 (8.3%) | 1 | 1/8 (12.5%) | 1 |
Respiratory, thoracic and mediastinal disorders | ||||
Hyperventilation | 0/12 (0%) | 0 | 1/8 (12.5%) | 1 |
Other (Not Including Serious) Adverse Events |
||||
Participants With Invasive Candidiasis | Participants With Aspergillosis | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 10/12 (83.3%) | 5/8 (62.5%) | ||
Blood and lymphatic system disorders | ||||
Anaemia | 1/12 (8.3%) | 1 | 0/8 (0%) | 0 |
Bone Marrow Failure | 1/12 (8.3%) | 1 | 0/8 (0%) | 0 |
Febrile Neutropenia | 1/12 (8.3%) | 1 | 0/8 (0%) | 0 |
Eye disorders | ||||
Ocular Icterus | 1/12 (8.3%) | 1 | 0/8 (0%) | 0 |
Gastrointestinal disorders | ||||
Abdominal Discomfort | 1/12 (8.3%) | 1 | 0/8 (0%) | 0 |
Abdominal Pain | 1/12 (8.3%) | 1 | 0/8 (0%) | 0 |
Diarrhoea | 1/12 (8.3%) | 1 | 0/8 (0%) | 0 |
Haematochezia | 2/12 (16.7%) | 2 | 0/8 (0%) | 0 |
Hypoaesthesia Oral | 1/12 (8.3%) | 1 | 0/8 (0%) | 0 |
Lower Gastrointestinal Haemorrhage | 0/12 (0%) | 0 | 1/8 (12.5%) | 1 |
Nausea | 1/12 (8.3%) | 1 | 0/8 (0%) | 0 |
Vomiting | 3/12 (25%) | 4 | 0/8 (0%) | 0 |
General disorders | ||||
Malaise | 1/12 (8.3%) | 1 | 0/8 (0%) | 0 |
Oedema | 1/12 (8.3%) | 1 | 0/8 (0%) | 0 |
Puncture Site Pain | 1/12 (8.3%) | 1 | 0/8 (0%) | 0 |
Pyrexia | 3/12 (25%) | 4 | 0/8 (0%) | 0 |
Vessel Puncture Site Inflammation | 1/12 (8.3%) | 1 | 0/8 (0%) | 0 |
Hepatobiliary disorders | ||||
Hepatic Function Abnormal | 2/12 (16.7%) | 2 | 1/8 (12.5%) | 1 |
Infections and infestations | ||||
Bacterial Infection | 0/12 (0%) | 0 | 1/8 (12.5%) | 1 |
Pseudomembranous Colitis | 0/12 (0%) | 0 | 1/8 (12.5%) | 1 |
Injury, poisoning and procedural complications | ||||
Contusion | 1/12 (8.3%) | 1 | 0/8 (0%) | 0 |
Excoriation | 1/12 (8.3%) | 1 | 0/8 (0%) | 0 |
Investigations | ||||
Alanine Aminotransferase Increased | 4/12 (33.3%) | 5 | 1/8 (12.5%) | 1 |
Aspartate Aminotransferase Increased | 3/12 (25%) | 4 | 1/8 (12.5%) | 1 |
Blood Bilirubin Increased | 1/12 (8.3%) | 1 | 0/8 (0%) | 0 |
Blood Lactate Dehydrogenase Increased | 2/12 (16.7%) | 2 | 0/8 (0%) | 0 |
Blood Urine Present | 1/12 (8.3%) | 1 | 0/8 (0%) | 0 |
C-Reactive Protein Increased | 1/12 (8.3%) | 1 | 0/8 (0%) | 0 |
Gamma-Glutamyltransferase Increased | 3/12 (25%) | 3 | 0/8 (0%) | 0 |
Heart Rate Increased | 0/12 (0%) | 0 | 1/8 (12.5%) | 1 |
Platelet Count Increased | 1/12 (8.3%) | 1 | 0/8 (0%) | 0 |
White Blood Cell Count Increased | 1/12 (8.3%) | 1 | 0/8 (0%) | 0 |
Metabolism and nutrition disorders | ||||
Hyperkalaemia | 1/12 (8.3%) | 1 | 0/8 (0%) | 0 |
Hypocalcaemia | 0/12 (0%) | 0 | 1/8 (12.5%) | 1 |
Musculoskeletal and connective tissue disorders | ||||
Arthralgia | 1/12 (8.3%) | 1 | 1/8 (12.5%) | 1 |
Myalgia | 1/12 (8.3%) | 1 | 0/8 (0%) | 0 |
Nervous system disorders | ||||
Headache | 2/12 (16.7%) | 3 | 0/8 (0%) | 0 |
Renal and urinary disorders | ||||
Renal Impairment | 1/12 (8.3%) | 1 | 0/8 (0%) | 0 |
Respiratory, thoracic and mediastinal disorders | ||||
Cough | 1/12 (8.3%) | 1 | 0/8 (0%) | 0 |
Pulmonary Oedema | 1/12 (8.3%) | 1 | 0/8 (0%) | 0 |
Upper Respiratory Tract Inflammation | 0/12 (0%) | 0 | 1/8 (12.5%) | 1 |
Skin and subcutaneous tissue disorders | ||||
Pruritus | 1/12 (8.3%) | 1 | 0/8 (0%) | 0 |
Rash | 4/12 (33.3%) | 7 | 1/8 (12.5%) | 1 |
Vascular disorders | ||||
Angiopathy | 1/12 (8.3%) | 1 | 0/8 (0%) | 0 |
Venoocclusive Disease | 0/12 (0%) | 0 | 1/8 (12.5%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to publication or presentation. Any information identified by the sponsor as confidential must be deleted prior to submission.
Results Point of Contact
Name/Title | Senior Vice President, Global Clinical Development |
---|---|
Organization | Merck Sharp & Dohme Corp |
Phone | 1-800-672-6372 |
ClinicalTrialsDisclosure@merck.com |
- 0991-074
- 132240