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Study To Assess Pharmacokinetics, Safety & Efficacy of Anidulafungin When Treating Children With Invasive Candidiasis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00761267
Recruitment Status : Completed
First Posted : September 29, 2008
Results First Posted : September 14, 2018
Last Update Posted : April 4, 2019
Sponsor:
Information provided by (Responsible Party):
Pfizer

Brief Summary:
Prospective, open label study to assess the pharmacokinetics, safety & efficacy of anidulafungin when used to treat children (aged 1 month - <18 years) with invasive candidiasis, including candidemia (ICC).

Condition or disease Intervention/treatment Phase
Candidemia Drug: Anidulafungin Drug: Fluconazole Phase 3

Detailed Description:
Prospective, open label study to assess the pharmacokinetics, safety & efficacy of anidulafungin when used to treat children (aged 1 month - < 18 years) with invasive candidiasis, including candidemia (ICC). To participate in the study, at the time of enrollment subjects must (1) have either a confirmed diagnosis of ICC or mycological evidence highly suggestive of Candida sp or (2) in infants 1 month to < 2 years only, be at high risk of candidiasis. All subjects meeting screening criteria receive IV anidulafungin. Subjects will be stratified by age (1 month - < 2 years; 2 years - < 5 years; 5 years - < 18 years). Subjects may be switched to oral fluconazole, provided that the pre-specified criteria are met. Subjects with microbiologically confirmed ICC must have a minimum total treatment duration of 14 days. The maximum allowed treatment duration of anidulafungin is 35 days; the maximum total treatment duration for the study is 49 days. At selected centers, anidulafungin pharmacokinetics will be assessed in the first 6 subjects age 1 month - < 2 years to confirm the recommended dosage regimen. A population PK-PD analysis will be performed in all other enrolled subjects. Subjects will be followed for safety through 6 week FU visit. Efficacy for subjects with confirmed ICC will be assessed at EOIVT, EOT, 2-week FU and 6-week FU visits.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 70 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A PROSPECTIVE, OPEN-LABEL STUDY TO ASSESS THE PHARMACOKINETICS, SAFETY & EFFICACY OF ANIDULAFUNGIN WHEN USED TO TREAT CHILDREN WITH INVASIVE CANDIDIASIS, INCLUDING CANDIDEMIA
Actual Study Start Date : February 2009
Actual Primary Completion Date : February 2018
Actual Study Completion Date : February 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Yeast Infections

Arm Intervention/treatment
Experimental: Anidulafungin IV
All subjects meeting screening criteria will receive IV anidulafungin.
Drug: Anidulafungin

Day 1: loading dose of 3 mg/kg (not to exceed 200 mg) Day 2 onwards: maintain a dose of 1.5 mg/kg (not to exceed 100 mg). Minimum total treatment duration is 14 days. Minimum IV anidulafungin treatment duration is 10 days for subjects with microbiologically confirmed ICC and 5 days for subjects at risk of candidiasis; followed by oral fluconazole 6-12 mg/kg/day (not to exceed 800mg/day).

Maximum treatment duration with anidulafungin is 35 days.

Other Name: Eraxis

Drug: Fluconazole
Subjects may be switched to oral fluconazole [6-12 mg/kg/day (not to exceed 800mg/day] provided they meet specified criteria. Maximum total treatment duration is 49 days.
Other Name: Diflucan




Primary Outcome Measures :
  1. Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Baseline up to 6 weeks after EOT (up to 91 days) ]
    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 6 weeks after end of treatment (EOT) (up to 91 days) that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and non-SAEs. EOT visit defined as last day of study treatment (IV or oral).

  2. Number of Participants With Laboratory Abnormalities [ Time Frame: Baseline up to 6 weeks after EOT (up to 91 days) ]
    Criteria for laboratory abnormalities: Hematology parameters: red blood cell count: <0.8*lower limit of normal (LLN); reticulocytes count (absolute or percent): <0.5*LLN or greater than (>) 1.5*upper limit of normal (ULN); Platelets: <0.5*LLN or >1.75*ULN; white blood cell count: <0.6*LLN or >1.5*ULN; neutrophils (absolute or percent): <0.8*LLN or >1.2*ULN; basophils (absolute or percent): >1.2*ULN; lymphocytes (absolute or percent): <0.8*LLN or >1.2*ULN; monocytes (absolute or percent): >1.2*ULN. Serum Chemistry parameters: sodium: <0.95*LLN or >1.05*ULN, potassium, chloride, bicarbonate, calcium: <0.9*LLN or >1.1*ULN; magnesium: >1.1*ULN or <0.9*LLN; BUN (blood urea nitrogen): >1.3* ULN, creatinine: >1.3*ULN; aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase : >3.0*ULN ; total bilirubin: >1.5*ULN; albumin: <0.8*LLN or >1.2*ULN and glucose: <0.6*LLN or >1.5*ULN.EOT visit defined as last day of study treatment (IV or oral).


Secondary Outcome Measures :
  1. Number of Participants With Global Response [ Time Frame: End of intravenous treatment (EOIVT) (maximum of 35 days), EOT (maximum of 49 days), during 2 week follow-up after EOT (up to 63 days) and during 6 week follow-up after EOT (up to 91 days) ]
    Global response categorized: success, failure, indeterminate.Success:clinical response(CR) of cure(resolution of sign, symptoms attributed to Candida infection[CI]; no additional systemic/oral antifungal) or improvement (significant but incomplete resolution of signs symptoms of CI; no additional systemic antifungal) and microbiological eradication/presumed eradication(Baseline pathogen not isolated from original site culture/culture data not available for participant with successful outcome).Failure:CR of failure(no significant improvement in signs symptoms/ death due to CI)and/or microbiological failure(persistence/new infection at follow-up/relapse of infection at follow-up). Indeterminate:CR of indeterminate(evaluation not made or failure assessment)and/or microbiological response of indeterminate(Culture data not available for participant with clinical outcome of indeterminate) and neither response was failure.EOT visit:last day of study treatment (IV or oral).

  2. Area Under the Plasma Concentration Versus Time Curve From Time Zero to 24 Hours (AUC24) of Anidulafungin for Pharmacokinetic (PK) Subgroup [ Time Frame: Day 2: Just prior to the start of infusion, 2 minutes before the end of infusion, 6, 12 and 24 hours after the start of infusion ]
    Non-compartmental PK analysis was performed on individual plasma anidulafungin concentration-time data collected by serial sampling from participants in the PK sub-study. AUC24 was calculated based on the trapezoidal rule.

  3. Maximum Plasma Concentration (Cmax) of Anidulafungin for Pharmacokinetic (PK) Subgroup [ Time Frame: Day 2: Just prior to the start of infusion, 2 minutes before the end of infusion, 6, 12, and 24 hours after the start of infusion ]
    Cmax was obtained directly from the observed concentration data on Day 2.

  4. Area Under the Plasma Concentration Versus Time Curve From Time Zero to 24 Hours (AUC24) of Polysorbate 80 (PS 80) Following Infusion of Anidulafungin for PK Subgroup [ Time Frame: Day 1: 0 to 2 hours post dose; Day 3 and Day 9:pre-dose; Day 5: 0 to 3 hours post dose; Day 7: 6 to 12 hours and 24 hours delayed post-dose ]
    Excipient PS 80 is a solubilizing agent contained in the IV formulation of anidulafungin. The lower limit of quantitation (LLOQ) for all the observations of PS 80 was 5.0 microgram per milliliter (mcg/mL). PK time points were assessed on Day 1, Day 3, Day 5, Day 7 and Day 9. Summarized data for all the time points was reported.

  5. Maximum Plasma Concentration (Cmax) of Polysorbate 80 (PS 80) Following Infusion of Anidulafungin for PK Subgroup [ Time Frame: Day 1: 0 to 2 hours post dose; Day 3 and Day 9:pre-dose; Day 5: 0 to 3 hours post dose; Day 7: 6 to 12 hours delayed post-dose ]
    Excipient PS 80 is a solubilizing agent contained in the IV formulation of anidulafungin. The lower limit of quantitation (LLOQ) for all the observations of PS 80 was 5.0 mcg/ml. PK time points were assessed on at Day 1, Day 3, Day 5, Day 7 and Day 9. Summarized data for all the time points was reported.

  6. Estimated Area Under the Plasma Curve Over a 24-Hour Dosing Interval at Steady State (AUC0-24ss) of Anidulafungin [ Time Frame: Sparse Sampling:Day 1:0-2 hr after end of infusion (EOI); Day3&9:pre-dose;Day 5:0-3hr post EOI; Day 7:6-12hr after EOI.For 1st 6 infants:< 2 years:Day 1:2 minutes before EOI; Day 2:pre infusion, 2 minutes before EOI, 6, 12,24 hours after start of infusion ]
    AUC24 values were calculated using the individual parameter estimates obtained from the final population PK model. PK time points were assessed on Days 1-3, Day 5, Day 7, and Day 9. Data for all time points were included in the model.

  7. Estimated Minimum Plasma Concentration (Cmin) of Anidulafungin [ Time Frame: Sparse Sampling:Day 1:0-2 hr after end of infusion (EOI); Day3&9:pre-dose;Day 5:0-3hr post EOI; Day 7:6-12hr after EOI.For 1st 6 infants:< 2 years:Day 1:2 minutes before EOI; Day 2:pre infusion, 2 minutes before EOI, 6, 12,24 hours after start of infusion ]
    Cmin values were calculated using the individual parameter estimates obtained from the final population PK model. PK time points were assessed on Days 1-3, Day 5, Day 7, and Day 9. Data for all time points were included in the model.

  8. Number of Participants With Greater Than or Equal to 1 Hepatic Adverse Event Categorized on the Basis of Exposure to Anidulafungin (AUC0-24,ss) [ Time Frame: Baseline to End of intravenous treatment (EOIVT) (maximum of 35 days) ]
    The probability of having at least one hepatic adverse event was compared with AUC0-24,ss quantile. Individual parameter estimates from the final PK model were used for estimation of Anidulafungin exposures.

  9. Number of Participants With Greater Than or Equal to 1 Gastro-Intestinal (GI) Adverse Event Categorized on the Basis of Exposure to Anidulafungin (AUC0-24,ss) [ Time Frame: Baseline to EOIVT (maximum of 35 days) ]
    The probability of having at least one GI adverse event whilst on Anidulafungin treatment was compared with AUC0-24,ss quantile. Individual parameter estimates from the final PK model were used for estimation of Anidulafungin exposures.

  10. Percentage of Participants With Global Response Categorized on the Basis of Exposure to Anidulafungin (AUC0-24,ss) [ Time Frame: EOIVT (maximum of 35 days) and EOT (maximum of 49 days) ]
    The probabilities of a global response of success or failure were compared with AUC0-24,ss quantile. Individual parameter estimates from the final PK model were used for estimation of Anidulafungin exposures. For the analysis of this outcome measure, global response was categorized as: success or failure. Success defined as clinical response (CR) of cure (resolution of signs, symptoms attributed to Candida infection [CI]). Failure defined as CR of failure (no significant improvement in signs symptoms/ death due to CI) and/or microbiological failure (persistence/new infection at follow-up/relapse of infection at follow-up).

  11. Percentage of Participants With Relapsed Response [ Time Frame: During 2 week follow-up after EOT (up to 63 days) and during 6 week follow-up after EOT (up to 91 days) ]
    Relapse was defined as any baseline Candida species isolated following eradication (documented or presumed); or culture data not available for a participant with a clinical response of failure after a previous response of success. Clinical response of failure was defined as no significant improvement in signs and symptoms, or death due to the Candida infection. Participants had received at least 3 doses of study medication to be classified as a failure. Clinical response of success was defined as resolution of sign and symptoms attributed to Candida infection occurred with no additional systemic or oral antifungal treatment required to complete the course of therapy. Eradication or presumed eradication: baseline pathogen not isolated from original site culture(s), or culture data are not available for a participant with successful clinical outcome. End of treatment visit defined as last day of study treatment (IV or oral).

  12. Percentage of Participants With New Infection [ Time Frame: During 2 week follow-up (up to 63 days) and 6 week follow-up (up to 91 days) after EOT ]
    New infection was defined as a participant presenting with clinical failure with the emergence of new Candida species at the original site of infection or at a distant site of infection. Clinical response of failure was defined as no significant improvement in signs and symptoms, or death due to the Candida infection occurred. Participants had received at least 3 doses of study medication to be classified as a failure. End of treatment visit defined as last day of study treatment (IV or oral).

  13. All-Cause Mortality - Number of Participants Who Died During Overall Study Treatment Period and Follow-Up Visits [ Time Frame: Overall treatment period (up to 49 days); during 2 week follow-up after EOT (up to 63 days) and during 6 week follow-up after EOT (up to 91 days) ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   1 Month to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subject must be either (1) at high risk for candidiasis (1 month - < 2 years ONLY) or (2) have a definitive diagnosis of invasive candidiasis/candidemia (ICC) (All age groups)
  • Male and female patients from 1 month to less than 18 years of age.

Exclusion Criteria:

  • Any patients with allergy to the drug; and any pregnant female or lactating.
  • Failed previous antifungal therapy or expected to live < 3 days.
  • Patients with documented or suspected Candida meningitis.

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): NCT00761267


Locations
Show Show 45 study locations
Sponsors and Collaborators
Pfizer
Investigators
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Study Director: Pfizer CT.gov Call Center Pfizer
  Study Documents (Full-Text)

Documents provided by Pfizer:
Study Protocol  [PDF] September 16, 2016
Statistical Analysis Plan  [PDF] October 5, 2016


Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00761267    
Other Study ID Numbers: A8851008
2008-004150-32 ( EudraCT Number )
First Posted: September 29, 2008    Key Record Dates
Results First Posted: September 14, 2018
Last Update Posted: April 4, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Pfizer:
Anidulafungin
pediatrics
candidemia
invasive candidiasis
safety
Additional relevant MeSH terms:
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Candidiasis
Candidemia
Candidiasis, Invasive
Mycoses
Fungemia
Sepsis
Infection
Invasive Fungal Infections
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes
Fluconazole
Anidulafungin
Antifungal Agents
Anti-Infective Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 CYP2C9 Inhibitors
Cytochrome P-450 CYP2C19 Inhibitors