- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03421002
Determination of Levels of Micafungin in Neonates Suffering From Systemic Candidiasis and/or Candida Meningitis
April 15, 2019 updated by: Astellas Pharma Global Development, Inc.
Determination of Plasmatic and CSF Levels of High Doses of Micafungin in Neonates Suffering From Systemic Candidiasis and/or Candida Meningitis
The primary purpose of this study is to evaluate the pharmacokinetic profile of micafungin administered to neonates suffering from systemic candidiasis.
This study will also evaluate the proportion of success and of failure of the therapy with micafungin among treated neonates and will identify a conversion factor to relate plasma levels of micafungin into capillary and venous blood measured through blood samples from the heel and from a peripheral vein, collected simultaneously.
Safety of micafungin in neonates will also be assessed.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
35
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
-
Rome, Italy, 00146
- Site IT39001
-
Rome, Italy, 00186
- Site IT39002
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
1 day to 5 months (CHILD)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Infection by systemic candidiasis Systemic candidiasis is diagnosed in case of worsening of clinical conditions while on therapy with antibiotics, in case of isolation of candida from at least one sample collected from a normally sterile site (Blood, CSF, Urine, Peritoneal Fluid) and/or from at least two non contiguous sites (tracheal aspirate, gastric aspirate, faeces) and/or positivity to candida through polymerase chain reaction (PCR)(Septifast test), associated with at least one clinical symptom (fever or hypothermia, mottled skin, feeding difficulties, muscular hypotonia or hypertonia, apnoea crisis, bradycardia, tachycardia, hypotension, dyspnea, polypnea, desaturation) and one laboratory symptom (white blood cell [WBC] ≤5000/mm3 or WBC ≥20.000/mm3, immature to total neutrophil ratio [I/T ratio] >2, Platelet count ≤100.000/mm3, C-reactive Protein >0,5 mg/dL, Standard Base Excess >-7 mmol/L, CSF pleocytosis-cells ≥ 6) and/or positivity to test Enzyme Linked Immuno-Sorbent Assay (ELISA) for the mannan antigen (≥125 pg/ml).
- Neonates affected by candida meningitis and/or hydrocephalus due to candida infection and/or bearing external ventricular derivation, until enrollment of at least 4 subjects with this characteristics.
- Parents of neonates, or legal representative, able to consent and comply with protocol requirements.
- Survival expectation not inferior to 3 days.
Exclusion Criteria:
- Acute hepatopathy (ammonium > 200 µg/dL) or chronic hepatopathy.
- Known allergy or hypersensitivity to echinocandins or any of the excipients present in the formulation of the investigational product.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Micafungin
Participants will receive micafungin 8 mg/kg per day via intravenous infusion for approximately 1 hour.
Micafungin will be administered for a minimum of 14 days until 1 of the following conditions applied: •Negative results (absence of Candida growth) from at least 2 consecutive blood cultures and/or resolution of clinical and laboratory symptoms and reduction of mannan antigen blood level (< 125 pg/mL) are obtained.
•In case of meningitis, hydrocephalus and external ventricular derivation, negative results (absence of Candida growth) from at least 2 consecutive cerebral spinal fluid (CSF) cultures associated with resolution of clinical and laboratory symptoms.
•Interruption (including addition or switch to another antifungal agent or dosage change of micafungin) due to demonstration of therapy failure.
|
Participants will receive micafungin 8 mg/kg per day via intravenous infusion for approximately 1 hour.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Concentration of Micafungin in Blood
Time Frame: Predose and after 1, 3, and 8 hours post-dose on one of treatment days from Day 3 to Day 10
|
Concentration will be determined from the pharmacokinetic (PK) blood samples collected via capillary micro-method (draws from the heel).
|
Predose and after 1, 3, and 8 hours post-dose on one of treatment days from Day 3 to Day 10
|
Concentration of Micafungin in Cerebral Spinal Fluid (CSF)
Time Frame: Predose and after 1, 3, and 8 hours post-dose on one of treatment days from Day 3 to Day 10
|
Concentration will be determined from the from the CSF samples collected.
|
Predose and after 1, 3, and 8 hours post-dose on one of treatment days from Day 3 to Day 10
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of Participants with a Response at End of Treatment (EOT) - Success of Therapy (SOT)
Time Frame: Up to day 14
|
For systemic candidiasis (SC) participants, SOT will be determined by survival associated with negative Candida test results of 2 consecutive blood cultures, completed at start of treatment, or resolution of clinical & laboratory symptoms together with reduction of mannan antigen blood level (MABL) (<125 pg/ml).
For Candida meningitis (CM), SOT will be determined by survival associated with negative Candida test results of at least 2 consecutive CSF cultures, completed at start of treatment and resolution of clinical and lab symptoms.
For hydrocephalus due to Candida infection (CI) and/or external ventricular derivation (EVD), SOT will be determined by survival associated with negative Candida test results of at least 2 consecutive CSF cultures, completed at start of treatment.
|
Up to day 14
|
Percentage of Participants with A Response at EOT - Failure of Therapy (FOT)
Time Frame: Up to day 14
|
For SC participants, FOT will be determined by death due to Candida sepsis, by confirmation of persistence of positive Candida test results from 1 blood culture completed by need to add/switch to another antifungal agent (AA) and/or change of micafungin dose for resolution of infection at any time or by the persistence of Candida colonization in different indicated sites associated with persistence of clinical and lab symptoms and with high (MABL) (≥ 125 pg/ml).
For CM, FOT will be determined by death due to CM, by persistence of CI from confirmation of positive CSF culture or by need to add/switch to another AA or dose change of micafungin for resolution of CI at any time.
For hydrocephalus due to CI and/or EVD, FOT will be determined by death due to CI, by need to add/switch to another AA or dose change of micafungin for resolution of CI at any time or by persistence of CI from confirmation of positive CSF culture.
|
Up to day 14
|
Number of Participants with Adverse Events (AEs)
Time Frame: From the first dose of study drug administration up 72 hours after the last dose, up to 17 days
|
An adverse event (AE) will be defined as any untoward medical occurrence in a participant administered a study drug or who will undergo study procedures which may not necessarily have a causal relationship with this treatment.
This includes abnormal laboratory tests, vital signs, electrocardiogram data or physical examinations that are defined as AEs if the abnormality will induce clinical signs or symptoms, require active intervention, interruption or discontinuation of study drug or may be clinically significant in the investigator's opinion.
The following standard with 3 grades will be used to measure the severity of AEs, including abnormal clinical laboratory values: ● Mild: No disruption of normal daily activities ● Moderate: Affected normal daily activities ● Severe: Inability to perform daily activities.
A treatment-emergent adverse event (TEAE) will be defined as an AE observed after starting administration of the test drug/comparative drug.
|
From the first dose of study drug administration up 72 hours after the last dose, up to 17 days
|
Comparison of Capillary and Venous Plasma Concentrations of Micafungin
Time Frame: Predose and after 1, 3, and 8 hours post-dose on one of treatment days from Day 3 to Day 10
|
Micafungin concentrations will be determined from the PK blood samples collected via both capillary micro-method (draws from the heel) and venous methods.
|
Predose and after 1, 3, and 8 hours post-dose on one of treatment days from Day 3 to Day 10
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (ACTUAL)
May 30, 2015
Primary Completion (ACTUAL)
April 10, 2018
Study Completion (ACTUAL)
April 10, 2018
Study Registration Dates
First Submitted
January 9, 2018
First Submitted That Met QC Criteria
January 29, 2018
First Posted (ACTUAL)
February 5, 2018
Study Record Updates
Last Update Posted (ACTUAL)
April 18, 2019
Last Update Submitted That Met QC Criteria
April 15, 2019
Last Verified
April 1, 2019
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 9463-CL-6001
- 2014-003087-20 (EUDRACT_NUMBER)
- 800_OPBG_2014 (OTHER: Ospedale Pediatrico Bambino Gesu Clinical & Research Center)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
IPD Plan Description
Access to anonymized individual participant level data will not be provided for this trial as it meets one or more of the exceptions described on www.clinicalstudydatarequest.com under "Sponsor Specific Details for Astellas."
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Candidiasis, Systemic
-
University Children's Hospital TuebingenCompletedSystemic Candidiasis | Systemic AspergillosisGermany
-
Astellas Pharma IncCompletedCandidemia | Invasive Candidiasis | Esophageal Candidiasis | Oropharyngeal CandidiasisUnited States, South Africa
-
Astellas Pharma IncCompletedCandidemia | Invasive Candidiasis | Esophageal Candidiasis | Oropharyngeal CandidiasisUnited States
-
Fujian Shengdi Pharmaceutical Co., Ltd.Not yet recruitingPatients With Candidemia and/or Invasive Candidiasis
-
Arkansas Children's Hospital Research InstituteChildren's Hospital of Philadelphia; St. Jude Children's Research Hospital; George... and other collaboratorsRecruitingInvasive CandidiasisUnited States
-
Basilea PharmaceuticaNot yet recruitingCandidemia | Candidiasis, Invasive
-
PfizerCompletedCandidemiaUnited States, Taiwan, Spain, United Kingdom, Korea, Republic of, Brazil, Greece, Canada, Italy, Russian Federation
-
Astellas Pharma IncCompletedCandidiasisUnited Kingdom, Austria, France, Germany, Italy, Poland, Spain, Sweden
-
PfizerTerminatedCandidemia | Invasive Candidiasis
Clinical Trials on Micafungin
-
Seoul National University HospitalUnknownNeutropenia | Fungal DiseaseKorea, Republic of
-
University Hospital, LimogesCompletedInvasive CandidiasisFrance
-
Radboud University Medical CenterCompletedInvasive Fungal InfectionNetherlands
-
Shandong Provincial HospitalRecruitingHematological Tumors Patients With High Risk Factors of Invasive Fungal DiseaseChina
-
Astellas Pharma IncCompletedCandidemia | Invasive Candidiasis | Esophageal Candidiasis | Oropharyngeal CandidiasisUnited States
-
Radboud University Medical CenterCompletedAllogeneic Stem Cell Transplant | Acute Myeloid Leucaemia | Myelo Dysplastic Syndrome | Acute Graft Versus Host Disease Grade II-IVNetherlands, Belgium
-
Astellas Pharma IncCompletedMycosesBelgium, Germany, Spain, France, Italy, Turkey, Austria, Switzerland, Hungary, United Kingdom, Israel, Denmark, Greece, Finland, Romania
-
Astellas Pharma Singapore Pte. Ltd.CompletedInvasive Fungal InfectionsHong Kong, Korea, Republic of, Singapore, Taiwan, Thailand
-
Eunice Kennedy Shriver National Institute of Child...Terminated
-
Gary E. Stein, Pharm.D.Astellas Pharma US, Inc.CompletedCandidemiaUnited States