A Study of Caspofungin (MK-0991) in Japanese Children and Adolescents With Documented Candida or Aspergillus Infections (MK-0991-074)

Sponsor
Merck Sharp & Dohme LLC (Industry)
Overall Status
Completed
CT.gov ID
NCT01165320
Collaborator
(none)
20
3
38.4

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

Study Type:
Interventional
Actual Enrollment :
20 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Multicenter, Noncomparative, Open-label Study to Estimate the Safety, Efficacy, and Pharmacokinetics of MK-0991 (Caspofungin) in Japanese Children and Adolescents With Documented Candida or Aspergillus Infections
Actual Study Start Date :
Jul 6, 2010
Actual Primary Completion Date :
Sep 17, 2013
Actual Study Completion Date :
Sep 17, 2013

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:
  • MK-0991
  • CANCIDAS®
  • 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:
  • MK-0991
  • CANCIDAS®
  • 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:
  • MK-0991
  • CANCIDAS®
  • Outcome Measures

    Primary Outcome Measures

    1. 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.

    2. 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

    Ages Eligible for Study:
    3 Months to 17 Years
    Sexes Eligible for Study:
    All
    Accepts 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

    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.
    Responsible Party:
    Merck Sharp & Dohme LLC
    ClinicalTrials.gov Identifier:
    NCT01165320
    Other Study ID Numbers:
    • 0991-074
    • 132240
    First Posted:
    Jul 19, 2010
    Last Update Posted:
    Aug 27, 2018
    Last Verified:
    Jul 1, 2018
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Additional relevant MeSH terms:

    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

    1. Primary Outcome
    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%
    2. Primary Outcome
    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

    [Not Specified]

    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
    Email ClinicalTrialsDisclosure@merck.com
    Responsible Party:
    Merck Sharp & Dohme LLC
    ClinicalTrials.gov Identifier:
    NCT01165320
    Other Study ID Numbers:
    • 0991-074
    • 132240
    First Posted:
    Jul 19, 2010
    Last Update Posted:
    Aug 27, 2018
    Last Verified:
    Jul 1, 2018