Clinical trial NCT00761267: Study To Assess Pharmacokinetics, Safety & Efficacy of Anidulafungin When Treating Children With Invasive Candidiasis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Candidemia
Keywords: Anidulafungin
pediatrics
candidemia
invasive candidiasis
safety
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2008-09-29
Enrollment: 70
Sex: ALL
Minimum age (years): 1
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

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.

Eligibility 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.

Primary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline up to 6 weeks after EOT (up to 91 days)
measure: Number of Participants With Laboratory Abnormalities
timeFrame: Baseline up to 6 weeks after EOT (up to 91 days)
Secondary outcomes:
measure: Number of Participants With Global Response
timeFrame: 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)
measure: Area Under the Plasma Concentration Versus Time Curve From Time Zero to 24 Hours (AUC24) of Anidulafungin for Pharmacokinetic (PK) Subgroup
timeFrame: 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
measure: Maximum Plasma Concentration (Cmax) of Anidulafungin for Pharmacokinetic (PK) Subgroup
timeFrame: 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
measure: 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
timeFrame: 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
measure: Maximum Plasma Concentration (Cmax) of Polysorbate 80 (PS 80) Following Infusion of Anidulafungin for PK Subgroup
timeFrame: 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
measure: Estimated Area Under the Plasma Curve Over a 24-Hour Dosing Interval at Steady State (AUC0-24ss) of Anidulafungin
timeFrame: 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
measure: Estimated Minimum Plasma Concentration (Cmin) of Anidulafungin
timeFrame: 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
measure: Number of Participants With Greater Than or Equal to 1 Hepatic Adverse Event Categorized on the Basis of Exposure to Anidulafungin (AUC0-24,ss)
timeFrame: Baseline to End of intravenous treatment (EOIVT) (maximum of 35 days)
measure: 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)
timeFrame: Baseline to EOIVT (maximum of 35 days)
measure: Percentage of Participants With Global Response Categorized on the Basis of Exposure to Anidulafungin (AUC0-24,ss)
timeFrame: EOIVT (maximum of 35 days) and EOT (maximum of 49 days)
measure: Percentage of Participants With Relapsed Response
timeFrame: During 2 week follow-up after EOT (up to 63 days) and during 6 week follow-up after EOT (up to 91 days)
measure: Percentage of Participants With New Infection
timeFrame: During 2 week follow-up (up to 63 days) and 6 week follow-up (up to 91 days) after EOT
measure: All-Cause Mortality - Number of Participants Who Died During Overall Study Treatment Period and Follow-Up Visits
timeFrame: 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)
Other outcomes:
Locations:
city: Long Beach
country: United States
facility: Miller Children's Hospital Bickerstaff Pediatric Family Center
state: California
city: Los Angeles
country: United States
facility: University of California - Los Angeles
state: California
city: Los Angeles
country: United States
facility: University of California - Los Angeles - Ronald Reagan Medical Center
state: California
city: Los Angeles
country: United States
facility: University of California - Los Angeles - Ronald Reagan UCLA Medical Center
state: California
city: Oakland
country: United States
facility: Children's Hospital & Research Center Oakland (CHRCO)
state: California
city: Orange
country: United States
facility: Children's Hospital of Orange County - Inpatient Pharmacy
state: California
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: Miami
country: United States
facility: Miami Children's Hospital
state: Florida
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals of Cleveland Laboratory University Hospitals Case Medical Center
state: Ohio
city: Memphis
country: United States
facility: Le Bonheur Children's Hospital - 4th Floor
state: Tennessee
city: Memphis
country: United States
facility: Le Bonheur Children's Hospital - 7th Floor lab
state: Tennessee
city: Memphis
country: United States
facility: LeBonheur Children's Hospital- Central Laboratory
state: Tennessee
city: Memphis
country: United States
facility: LeBonheur Children's Hospital
state: Tennessee
city: Memphis
country: United States
facility: Pediatric Clinical Research Unit University of Tennessee Health Science Center
state: Tennessee
city: Memphis
country: United States
facility: Pediatric Clinical Research Unit- 7th Floor Lab
state: Tennessee
city: Memphis
country: United States
facility: Pharmacy-University of Tennessee Health Science Center
state: Tennessee
city: Memphis
country: United States
facility: University of Tennessee Health Science Center
state: Tennessee
city: Memphis
country: United States
facility: University of Tennessee Medical Group Pediatrics
state: Tennessee
city: Memphis
country: United States
facility: University of Tennessee Health Science Center, Department of Ophthalmology
state: Tennessee
city: Fort Worth
country: United States
facility: Cook Children's Infectious Diseases Clinic
state: Texas
city: Fort Worth
country: United States
facility: Cook Children's Medical Center
state: Texas
city: Fort Worth
country: United States
facility: Infectious Diseases Clinic Cook Children's Medical Center
state: Texas
city: Milwaukee
country: United States
facility: Children's Hospital of Wisconsin
state: Wisconsin
city: Curitiba
country: Brazil
facility: Hospital de Clinicas da Universidade Federal do Parana
state: Paraná
city: Curitiba
country: Brazil
facility: Hospital Pequeno Principe
state: PR
city: Sao Paulo
country: Brazil
facility: Hospital Infantil Sabara / Fundacao Jose Luiz Egydio Setubal
state: SP
city: Sao Paulo
country: Brazil
facility: Instituto PENSI - Pesquisa e Ensino em Saúde Infantil
state: SP
city: Sao Paulo
country: Brazil
facility: Instituto de Oncologia Pediatrica - Grupo de Apoio ao Adolescente e a Crianca com Cancer
state: SP
city: Sao Paulo
country: Brazil
facility: Instituto de Oncologia Pediatrica - Grupo de Apoio ao Adolescente e a Crianca com Cancer
city: Edmonton
country: Canada
facility: Stollery Children's Hospital - University of Alberta
state: Alberta
city: Athens
country: Greece
facility: Aghia Sophia Childrens Hospital
city: Thessaloniki
country: Greece
facility: Hippokration Hospital
city: Roma
country: Italy
facility: Universita degli Studi di Roma La Sapienza
state: Province OF ROME
city: Roma
country: Italy
facility: IRCCS Ospedale Pediatrico Bambino Gesu
state: RM
city: Roma
country: Italy
facility: Universitario Ospedaliero IRCCS Ospedale Pediatrico Bambino Gesu
state: RM
city: Songpa-gu
country: Korea, Republic of
facility: Asan Medical Center
state: Seoul
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center, Department of Pharmacy
city: Moscow
country: Russian Federation
facility: National Cancer Research Center RAMS n.a. N.N. Blokhin; Laboratory Microbiological Diagnostics
city: Moscow
country: Russian Federation
facility: Fed. Scientific Center for Pediatric Hematology, Oncology and Immunology of Russian Healthcare Org.
city: Barcelona
country: Spain
facility: Hospital Vall D'Hebron
city: Kwei Shan Town
country: Taiwan
facility: Chang Gung Children's Hospital
state: Taoyuan County
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Nottingham
country: United Kingdom
facility: Nottingham Children's Hospital
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Roilides E, Carlesse F, Tawadrous M, Leister-Tebbe H, Conte U, Raber S, Swanson R, Yan JL, Aram JA, Queiroz-Telles F; Anidulafungin A8851008 Pediatric Study Group. Safety, Efficacy and Pharmacokinetics of Anidulafungin in Patients 1 Month to <2 Years of Age With Invasive Candidiasis, Including Candidemia. Pediatr Infect Dis J. 2020 Apr;39(4):305-309. doi: 10.1097/INF.0000000000002568.
citation: Roilides E, Carlesse F, Leister-Tebbe H, Conte U, Yan JL, Liu P, Tawadrous M, Aram JA, Queiroz-Telles F; Anidulafungin A8851008 Pediatric Study Group. A Prospective, Open-label Study to Assess the Safety, Tolerability and Efficacy of Anidulafungin in the Treatment of Invasive Candidiasis in Children 2 to <18 Years of Age. Pediatr Infect Dis J. 2019 Mar;38(3):275-279. doi: 10.1097/INF.0000000000002237.