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Determination of Levels of Micafungin in Neonates Suffering From Systemic Candidiasis and/or Candida Meningitis

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ClinicalTrials.gov Identifier: NCT03421002
Recruitment Status : Completed
First Posted : February 2, 2018
Last Update Posted : April 18, 2019
Sponsor:
Collaborator:
IRCCS, Ospedale Pediatrico Bambino Gesu
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Candidiasis, Systemic Candida Meningitis Drug: Micafungin Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 35 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Determination of Plasmatic and CSF Levels of High Doses of Micafungin in Neonates Suffering From Systemic Candidiasis and/or Candida Meningitis
Actual Study Start Date : May 30, 2015
Actual Primary Completion Date : April 10, 2018
Actual Study Completion Date : April 10, 2018

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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.
Drug: Micafungin
Participants will receive micafungin 8 mg/kg per day via intravenous infusion for approximately 1 hour.
Other Name: Mycamine




Primary Outcome Measures :
  1. 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).

  2. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.



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Ages Eligible for Study:   up to 180 Days   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03421002


Locations
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Italy
Site IT39001
Rome, Italy, 00146
Site IT39002
Rome, Italy, 00186
Sponsors and Collaborators
Astellas Pharma Global Development, Inc.
IRCCS, Ospedale Pediatrico Bambino Gesu
Investigators
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Study Director: Executive Medical Director Astellas Pharma Global Development, Inc.

Additional Information:
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Responsible Party: Astellas Pharma Global Development, Inc.
ClinicalTrials.gov Identifier: NCT03421002     History of Changes
Other Study ID Numbers: 9463-CL-6001
2014-003087-20 ( EudraCT Number )
800_OPBG_2014 ( Other Identifier: Ospedale Pediatrico Bambino Gesu Clinical & Research Center )
First Posted: February 2, 2018    Key Record Dates
Last Update Posted: April 18, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
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."

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. ):
candida meningitis
Mycamine
candidiasis, systemic
micafungin
Additional relevant MeSH terms:
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Candidiasis
Meningitis
Central Nervous System Diseases
Nervous System Diseases
Mycoses
Micafungin
Antifungal Agents
Anti-Infective Agents