Download PDF

Clinical Trial Results:
A Prospective, Open-Label Study To Assess The Pharmacokinetics, Safety & Efficacy Of Anidulafungin When Used To Treat Children With Invasive Candidiasis, Including Candidemia

Summary
EudraCT number	2008-004150-32
Trial protocol	ES DE FR PT IT GR Outside EU/EEA GB
Global end of trial date	14 Feb 2018

Results information
Results version number	v2(current)
This version publication date	19 May 2019
First version publication date	30 Aug 2018
Other versions	v1
Version creation reason

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

A8851008

ISRCTN number

US NCT number

NCT00761267

WHO universal trial number (UTN)

Sponsor organisation name

Pfizer, Inc.

Sponsor organisation address

235 E 42nd Street, New York, United States, NY 10017

Public contact

Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc., 001 18007181021, ClinicalTrials.gov_Inquiries@pfizer.com

Scientific contact

Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc., 001 18007181021, ClinicalTrials.gov_Inquiries@pfizer.com

Is trial part of an agreed paediatric investigation plan (PIP)

Yes

EMA paediatric investigation plan number(s)

EMEA-000469-PIP01-08

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Yes

Analysis stage

Final

Date of interim/final analysis

17 May 2018

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

14 Feb 2018

Was the trial ended prematurely?

Main objective of the trial

To evaluate the safety and tolerability of anidulafungin in children 1 month to less than (<) 18 years of age with invasive candidiasis, including candidemia (ICC).

Protection of trial subjects

The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Council for Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.

Background therapy

Evidence for comparator

Actual start date of recruitment

27 Feb 2009

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Brazil: 17

Country: Number of subjects enrolled

Canada: 1

Country: Number of subjects enrolled

Spain: 1

Country: Number of subjects enrolled

Greece: 13

Country: Number of subjects enrolled

Italy: 4

Country: Number of subjects enrolled

Korea, Republic of: 3

Country: Number of subjects enrolled

Russian Federation: 7

Country: Number of subjects enrolled

Taiwan: 3

Country: Number of subjects enrolled

United States: 18

Country: Number of subjects enrolled

United Kingdom: 1

Worldwide total number of subjects

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

Screening details

The study was conducted in 10 countries between 27 Feb 2009 and 14 Feb 2018.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Anidulafungin:Subjects Aged 1 month to less than(<)2 Years

Arm description

Subjects received Anidulafungin loading dose of 3 milligrams per kg(mg/kg) intravenously(IV) on Day 1 and maintenance dose of 1.5mg/kg, every 24 hours for maximum 35 days.After >=10 days treatment, subjects with microbiologically confirmed invasive candidiasis/candidemia(ICC) and who fulfilled protocol specified criteria [1)afebrile for >=24 hours, 2)tolerate oral medication, 3)documentation of 2 blood cultures [24 hours apart] negative for Candida, 4)eradication/presumed eradication of Candida from other infection sites,identified at enrollment,5)specific Candida isolate susceptible/presumed susceptible to fluconazole, 6)switched to oral fluconazole if improvement in signs,symptoms of Candida infection] and after >=5 days treatment, subjects without microbiologically confirmed ICC,could switch to oral fluconazole(6-12 mg/kg/day,maximum 800mg/day) upto 49 days.First 6 subjects received second antifungal agent, if required at Investigator’s discretion.

Arm type

Experimental

Investigational medicinal product name

Anidulafungin

Investigational medicinal product code

PF-03910960

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Anidulafungin at loading dose of 3mg/kg, IV on Day 1, then maintenance dose of 1.5 mg/kg, every 24 hours for maximum of 35 days.

Anidulafungin: Subjects Aged 2 to <5 Years

Arm description

Subjects received Anidulafungin loading dose of 3mg/kg, IV on Day 1 and maintenance dose of 1.5mg/kg, every 24 hours for minimum 10 and maximum 35 days. After >=10 days treatment, subjects with microbiologically confirmed ICC and who fulfilled protocol specified criteria [1)afebrile for >=24 2hours, 2)tolerate oral medication, 3)documentation of 2 blood cultures [24 hours apart] negative for Candida, 4)eradication/presumed eradication of Candida from other infection sites,identified at enrollment,5)specific Candida isolate susceptible/presumed susceptible to fluconazole, 6)switched to oral fluconazole if improvement in signs,symptoms of Candida infection] and after >=5 days treatment, subjects without microbiologically confirmed ICC, could switch to oral fluconazole (6-12 mg/kg/day, maximum 800mg/day) for upto 49 days.

Arm type

Experimental

Investigational medicinal product name

Anidulafungin

Investigational medicinal product code

PF-03910960

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Anidulafungin at loading dose of 3 mg/kg, IV on Day 1, then maintenance dose of 1.5 mg/kg, every 24 hours for a minimum of 10 days and maximum of 35 days.

Anidulafungin: Subjects Aged 5 to <18 Years

Arm description

Subjects received Anidulafungin loading dose of 3mg/kg, IV on Day 1 and maintenance dose of 1.5mg/kg, every 24 hours for minimum 10 and maximum 35 days. After >=10 days treatment, subjects with microbiologically confirmed ICC and who fulfilled protocol specified criteria ([1)afebrile for >=24 hours, 2)tolerate oral medication, 3)documentation of 2 blood cultures [24 hours apart] negative for Candida, 4)eradication/presumed eradication of Candida from other infection sites,identified at enrollment,5)specific Candida isolate susceptible/presumed susceptible to fluconazole, 6)switched to oral fluconazole if improvement in signs,symptoms of Candida infection]and after >=5 days treatment, subjects without microbiologically confirmed ICC, could switch to oral fluconazole (6-12 mg/kg/day, maximum 800mg/day) upto 49 days.

Arm type

Experimental

Investigational medicinal product name

Anidulafungin

Investigational medicinal product code

PF-03910960

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Anidulafungin at loading dose of 3 mg/kg, IV on Day 1, then maintenance dose of 1.5 mg/kg, every 24 hours for a minimum of 10 days and maximum of 35 days.

Number of subjects in period 1	Anidulafungin:Subjects Aged 1 month to less than(<)2 Years	Anidulafungin: Subjects Aged 2 to <5 Years	Anidulafungin: Subjects Aged 5 to <18 Years
Started	19	19	30
Completed	18	16	24
Not completed	1	3	6
Consent withdrawn by subject	-	1	-
Lost to follow-up	-	-	1
Subject Died	1	2	5

Baseline characteristics

Top of page

Reporting group title

Anidulafungin:Subjects Aged 1 month to less than(<)2 Years

Reporting group description

Reporting group title

Anidulafungin: Subjects Aged 2 to <5 Years

Reporting group description

Reporting group title

Anidulafungin: Subjects Aged 5 to <18 Years

Reporting group description

Subjects received Anidulafungin loading dose of 3mg/kg, IV on Day 1 and maintenance dose of 1.5mg/kg, every 24 hours for minimum 10 and maximum 35 days. After >=10 days treatment, subjects with microbiologically confirmed ICC and who fulfilled protocol specified criteria ([1)afebrile for >=24 hours, 2)tolerate oral medication, 3)documentation of 2 blood cultures [24 hours apart] negative for Candida, 4)eradication/presumed eradication of Candida from other infection sites,identified at enrollment,5)specific Candida isolate susceptible/presumed susceptible to fluconazole, 6)switched to oral fluconazole if improvement in signs,symptoms of Candida infection]and after >=5 days treatment, subjects without microbiologically confirmed ICC, could switch to oral fluconazole (6-12 mg/kg/day, maximum 800mg/day) upto 49 days.

Reporting group values	Anidulafungin:Subjects Aged 1 month to less than(<)2 Years	Anidulafungin: Subjects Aged 2 to <5 Years	Anidulafungin: Subjects Aged 5 to <18 Years	Total
Number of subjects	19	19	30	68
Age categorical
Units: Subjects
In utero	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0
Newborns (0-27 days)	0	0	0	0
Infants and toddlers (28 days-23 months)	19	0	0	19
Children (2-11 years)	0	19	20	39
Adolescents (12-17 years)	0	0	10	10
Adults (18-64 years)	0	0	0	0
From 65-84 years	0	0	0	0
85 years and over	0	0	0	0
Age Continuous
Units: years
arithmetic mean (standard deviation)	0.93 ( 0.52 )	3.09 ( 0.68 )	10.67 ( 3.68 )	-
Sex: Female, Male
Units: Subjects
Female	9	8	13	30
Male	10	11	17	38
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	0	0	0	0
Asian	0	2	4	6
Native Hawaiian or Other Pacific Islander	0	0	0	0
Black or African American	0	1	0	1
White	19	15	20	54
More than one race	0	0	0	0
Unknown or Not Reported	0	1	6	7

End points

Top of page

Reporting group title

Anidulafungin:Subjects Aged 1 month to less than(<)2 Years

Reporting group description

Reporting group title

Anidulafungin: Subjects Aged 2 to <5 Years

Reporting group description

Reporting group title

Anidulafungin: Subjects Aged 5 to <18 Years

Reporting group description

Subjects received Anidulafungin loading dose of 3mg/kg, IV on Day 1 and maintenance dose of 1.5mg/kg, every 24 hours for minimum 10 and maximum 35 days. After >=10 days treatment, subjects with microbiologically confirmed ICC and who fulfilled protocol specified criteria ([1)afebrile for >=24 hours, 2)tolerate oral medication, 3)documentation of 2 blood cultures [24 hours apart] negative for Candida, 4)eradication/presumed eradication of Candida from other infection sites,identified at enrollment,5)specific Candida isolate susceptible/presumed susceptible to fluconazole, 6)switched to oral fluconazole if improvement in signs,symptoms of Candida infection]and after >=5 days treatment, subjects without microbiologically confirmed ICC, could switch to oral fluconazole (6-12 mg/kg/day, maximum 800mg/day) upto 49 days.

Subject analysis set title

Anidulafungin: First 6 subjects aged 1 month to <2 years

Subject analysis set type

Sub-group analysis

Subject analysis set description

First 6 subjects received Anidulafungin at loading dose of 3 mg/kg, IV on Day 1, then maintenance dose of 1.5 mg/kg, every 24 hours for maximum of 35 days.

Subject analysis set title

Anidulafungin PK subgroup of last eight: 1 month to <2 Years

Subject analysis set type

Sub-group analysis

Subject analysis set description

Last eight subjects received Anidulafungin loading dose of 3 mg/kg, IV on Day 1, then maintenance dose of 1.5 mg/kg, every 24 hours for minimum of 10 days and maximum of 35 days. After >=10 days of IV treatment, participants with microbiologically confirmed ICC and who fulfilled protocol specified criterion [1) afebrile for >=24 hours, 2) tolerate oral medication, 3)documentation of 2 blood cultures (24 hours apart) negative for Candida species,4) Eradication/presumed eradication of Candida species from any other sites of infection if identified at enrollment, 5) Specific Candida isolate was susceptible/presumed susceptible to fluconazole, 6) switched to oral fluconazole if improvement in signs, symptoms of Candida infection] received oral fluconazole (6 to 12 mg/kg/day, maximum 800 mg/day) up to 49 days. Subjects received a second systemic antifungal agent, if required at the Investigator’s discretion.

Subject analysis set title

Exposure response: Hepatic adverse events

Subject analysis set type

Sub-group analysis

Subject analysis set description

Exposure (AUC0-24ss) response quantile analysis for subjects with evaluable PK and hepatic adverse events whilst on receiving Anidulafungin therapy.

Subject analysis set title

Exposure response: Gastrointestinal (GI) adverse events

Subject analysis set type

Sub-group analysis

Subject analysis set description

Exposure (AUC0-24ss) response quantile analysis for subjects with evaluable PK and gastrointestinal adverse events whilst on receiving Anidulafungin therapy.

Subject analysis set title

Exposure response: Efficacy

Subject analysis set type

Sub-group analysis

Subject analysis set description

Exposure (AUC0-24ss) response quantile analysis for subjects with success or failure outcome in Global Response at End of IV treatment (EOIVT) and End of treatment (EOT). Subjects with indeterminate outcome were excluded.

Primary: Number of Subjects With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

Top of page

End point title

Number of Subjects With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) ^[1]

End point description

An AE was any untoward medical occurrence in a subject 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). The safety population included all randomized subjects who received at least 1 dose of study medication.

End point type

Primary

End point timeframe

Baseline up to 6 weeks after EOT (up to 91 days)

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be analyzed for this endpoint.

End point values	Anidulafungin:Subjects Aged 1 month to less than(<)2 Years	Anidulafungin: Subjects Aged 2 to <5 Years	Anidulafungin: Subjects Aged 5 to <18 Years
Number of subjects analysed	19	19	30
Units: subjects
AEs\|	17	19	30
SAEs\|	7	10	13

No statistical analyses for this end point

Primary: Number of Subjects with Laboratory Abnormalities

Top of page

End point title

Number of Subjects with Laboratory Abnormalities ^[2]

End point description

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.Safety population:all randomized subjects who received at least 1 dose of study medication.

End point type

Primary

End point timeframe

Baseline up to 6 weeks after EOT (up to 91 days)

Notes
[2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be analyzed for this endpoint.

End point values	Anidulafungin:Subjects Aged 1 month to less than(<)2 Years	Anidulafungin: Subjects Aged 2 to <5 Years	Anidulafungin: Subjects Aged 5 to <18 Years
Number of subjects analysed	19	19	30
Units: subjects	19	18	30

No statistical analyses for this end point

Secondary: Number of Subjects With Global Response

Top of page

End point title

Number of Subjects With Global Response

End point description

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 subject with successful outcome).Failure:CR of failure(no significant improvement in signs,symptoms/death due to CI)and/or microbiological failure(persistence/new infection/relapse at follow-up).Indeterminate:CR of indeterminate(evaluation not made due to withdrawal from study prior to cure or failure assessment)and/or microbiological response of indeterminate(Culture data not available for subject with clinical outcome of indeterminate)and neither response was failure.mITT population:atleast 1 dose of study drug with confirmation of CI.

End point type

Secondary

End point 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)

End point values	Anidulafungin:Subjects Aged 1 month to less than(<)2 Years	Anidulafungin: Subjects Aged 2 to <5 Years	Anidulafungin: Subjects Aged 5 to <18 Years
Number of subjects analysed	16	18	30
Units: subjects
EOIVT:Success	11	14	20
EOIVT:Failure	2	1	3
EOIVT:Indeterminate	3	3	7
EOIVT:Missing	0	0	0
EOT:Success	11	14	21
EOT:Failure	2	1	3
EOT:Indeterminate	3	3	6
EOT:Missing	0	0	0
2 week follow-up:Success	11	13	22
2 week follow-up:Failure	2	1	4
2 week follow-up:Indeterminate	3	1	0
2 week follow-up:Missing	0	3	4
6 week follow-up:Success	11	12	20
6 week follow-up:Failure	2	2	6
6 week follow-up:Indeterminate	3	2	0
6 week follow-up:Missing	0	2	4

No statistical analyses for this end point

Secondary: Area Under the Plasma Concentration Versus Time Curve From Time Zero to 24 Hours (AUC24) of Anidulafungin for Pharmacokinetic (PK) Subgroup

Top of page

End point title

Area Under the Plasma Concentration Versus Time Curve From Time Zero to 24 Hours (AUC24) of Anidulafungin for Pharmacokinetic (PK) Subgroup

End point description

Non-compartmental PK analysis was performed on individual plasma anidulafungin concentration-time data collected by serial sampling from subjects in the PK sub-study. AUC24 was calculated based on the trapezoidal rule. PK subgroup population included the first 6 subjects aged between 1 month to <2 years.

End point type

Secondary

End point 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

End point values	Anidulafungin: First 6 subjects aged 1 month to <2 years
Number of subjects analysed	6
Units: nanogramhour per milliliter (nghr/mL)
geometric mean (geometric coefficient of variation)	66449.1 ( 28 )

No statistical analyses for this end point

Secondary: Maximum Plasma Concentration (Cmax) of Anidulafungin for Pharmacokinetic (PK) Subgroup

Top of page

End point title

Maximum Plasma Concentration (Cmax) of Anidulafungin for Pharmacokinetic (PK) Subgroup

End point description

Cmax was obtained directly from the observed concentration data on Day 2. PK subgroup population included the first 6 subjects aged between 1 month to <2 years.

End point type

Secondary

End point 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

End point values	Anidulafungin: First 6 subjects aged 1 month to <2 years
Number of subjects analysed	6
Units: nanogram per milliliter (ng/mL)
geometric mean (geometric coefficient of variation)	5963.53 ( 29 )

No statistical analyses for this end point

Secondary: 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

Top of page

End point title

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 ^[3]

End point description

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). The geometric mean and coefficient of variation was not reported since only one value was above LLOQ, hence, AUC24 of polysorbate 80 could not be calculated and has been denoted by 99999. The PK subgroup population for PS80 included all subjects aged between 1 month to <2 years who had 1 or more PK sample available. PK time points were assessed on at Day 1, Day 2, Day 5, Day 7 and Day 9. Summarized data for all the time points was reported.

End point type

Secondary

End point 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

Notes
[3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only descriptive data was planned to be analyzed for this endpoint.

End point values	Anidulafungin:Subjects Aged 1 month to less than(<)2 Years
Number of subjects analysed	8
Units: ng*hr/mL
geometric mean (geometric coefficient of variation)	99999 ( 99999 )

No statistical analyses for this end point

Secondary: Maximum Plasma Concentration (Cmax) of Polysorbate 80 (PS 80) Following Infusion of Anidulafungin for PK Subgroup

Top of page

End point title

Maximum Plasma Concentration (Cmax) of Polysorbate 80 (PS 80) Following Infusion of Anidulafungin for PK Subgroup ^[4]

End point description

Excipient PS 80 is a solubilizing agent contained in the IV formulation of anidulafungin. The LLOQ for all the observations of PS 80 was 5.0 mcg/ml. The geometric mean and coefficient of variation was not reported since only one value was above LLOQ, hence, Cmax of polysorbate 80 could not be calculated and has been denoted by 99999. The PK subgroup population for PS80 included all subjects aged between 1 month to <2 years who had 1 or more PK sample available. PK time points were assessed on at Day 1, Day 2, Day 5, Day 7 and Day 9. Summarized data for all the time points was reported.

End point type

Secondary

End point 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

Notes
[4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only descriptive data was planned to be analyzed for this endpoint.

End point values	Anidulafungin:Subjects Aged 1 month to less than(<)2 Years
Number of subjects analysed	8
Units: ng/mL
geometric mean (geometric coefficient of variation)	99999 ( 99999 )

No statistical analyses for this end point

Secondary: Estimated Area Under the Plasma Curve Over a 24-Hour Dosing Interval at Steady State (AUC0-24ss) of Anidulafungin

Top of page

End point title

Estimated Area Under the Plasma Curve Over a 24-Hour Dosing Interval at Steady State (AUC0-24ss) of Anidulafungin

End point description

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. PK population included all those subjects who had 1 or more PK samples available.

End point type

Secondary

End point 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

End point values	Anidulafungin:Subjects Aged 1 month to less than(<)2 Years	Anidulafungin: Subjects Aged 2 to <5 Years	Anidulafungin: Subjects Aged 5 to <18 Years
Number of subjects analysed	17	19	30
Units: microgramhour per milliliter(mcghr/ml)
arithmetic mean (standard deviation)	69.87 ( 17.65 )	82.81 ( 31.9 )	86.77 ( 31.12 )

No statistical analyses for this end point

Secondary: Estimated Minimum Plasma Concentration (Cmin) of Anidulafungin

Top of page

End point title

Estimated Minimum Plasma Concentration (Cmin) of Anidulafungin

End point description

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.PK population included all those subjects who had 1 or more PK samples available.

End point type

Secondary

End point timeframe

End point values	Anidulafungin:Subjects Aged 1 month to less than(<)2 Years	Anidulafungin: Subjects Aged 2 to <5 Years	Anidulafungin: Subjects Aged 5 to <18 Years
Number of subjects analysed	17	19	30
Units: mcg/ml
arithmetic mean (standard deviation)	1.98 ( 0.58 )	2.51 ( 1.11 )	2.52 ( 0.96 )

No statistical analyses for this end point

Secondary: Number of Subjects with Greater Than or Equal to 1 Hepatic Adverse Event Categorized on the Basis of Exposure to Anidulafungin (AUC0-24,ss)

Top of page

End point title

Number of Subjects with Greater Than or Equal to 1 Hepatic Adverse Event Categorized on the Basis of Exposure to Anidulafungin (AUC0-24,ss)

End point description

In an analysis of subjects reporting one or more all-causality hepatic adverse event(s) versus AUC0-24ss (ug*hr/mL) in 5 quantiles, no exposure-response was observed, and has been denoted by '99999'. Analysis performed on all subjects who received at least one dose of the study treatment (Anidulafungin) and had paired PK and safety data available.

End point type

Secondary

End point timeframe

Baseline to End of intravenous treatment (EOIVT) (maximum of 35 days)

End point values	Exposure response: Hepatic adverse events
Number of subjects analysed	66
Units: subjects	99999

No statistical analyses for this end point

Secondary: Number of Subjects with Greater Than or Equal to 1 Gastro-Intestinal (GI) Adverse Event Categorized on the Basis of Exposure to Anidulafungin (AUC0-24,ss)

Top of page

End point title

Number of Subjects with Greater Than or Equal to 1 Gastro-Intestinal (GI) Adverse Event Categorized on the Basis of Exposure to Anidulafungin (AUC0-24,ss)

End point description

In an analysis of subjects reporting one or more all-causality gastrointestinal adverse event(s) versus AUC0-24ss (ug*hr/mL) in 5 quantiles, no exposure-response was observed, and has been denoted by '99999'. Analysis performed on all subjects who received at least one dose of the study treatment (Anidulafungin) and had paired PK and safety data available.

End point type

Secondary

End point timeframe

Baseline to EOIVT (maximum of 35 days)

End point values	Exposure response: Gastrointestinal (GI) adverse events
Number of subjects analysed	66
Units: subjects	99999

No statistical analyses for this end point

Secondary: Percentage of Participants With Global Response Categorized on the Basis of Exposure to Anidulafungin (AUC0-24,ss)

Top of page

End point title

Percentage of Participants With Global Response Categorized on the Basis of Exposure to Anidulafungin (AUC0-24,ss)

End point description

In an analysis of success/failure versus AUC0-24ss (ug*hr/mL) in 5 quantiles, no exposure-response was observed, and has been denoted by '99999'. Success was defined as clinical response (CR) of cure (resolution of signs, symptoms attributed to Candida infection) whilst failure was defined as no CR (no significant improvement in signs symptoms or death due to Candida infection) and or microbiological failure (persistence). The mITT population was defined as all subjects who had received at least 1 dose of study drug and who had microbiological confirmation of Candida infection and those with paired PK and response of success or failure available (indeterminate response subjects were excluded). Here, ‘n' = Subjects evaluable for this endpoint at specified categories.

End point type

Secondary

End point timeframe

EOIVT (maximum of 35 days) and EOT (maximum of 49 days)

End point values	Exposure response: Efficacy
Number of subjects analysed	50
Units: percentage of subjects
number (not applicable)
EOIVT (n=49)	99999
EOT (n=50)	99999

No statistical analyses for this end point

Secondary: Percentage of Subjects With Relapsed Response

Top of page

End point title

Percentage of Subjects With Relapsed Response

End point description

Relapse:any baseline Candida species isolated following eradication (documented or presumed); or culture data not available for a subject with a clinical response of failure after a previous response of success. Clinical response of failure:no significant improvement in signs and symptoms, or death due to the Candida infection (CI). Subjects had received at least 3 doses of study medication to be classified as a failure. Clinical response of success: 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 subject with successful clinical outcome. End of treatment visit defined as last day of study treatment (IV or oral).mITT population:subjects who received at least 1 dose of study drug and had microbiological confirmation of CI.

End point type

Secondary

End point timeframe

During 2 week follow-up after EOT (up to 63 days) and during 6 week follow-up after EOT (up to 91 days)

End point values	Anidulafungin:Subjects Aged 1 month to less than(<)2 Years	Anidulafungin: Subjects Aged 2 to <5 Years	Anidulafungin: Subjects Aged 5 to <18 Years
Number of subjects analysed	16	18	30
Units: percentage of subjects
number (not applicable)
2 week follow-up\|	0.0	0.0	0.0
6 week follow-up\|	0.0	5.6	6.7

No statistical analyses for this end point

Secondary: Percentage of Subjects With New Infection

Top of page

End point title

Percentage of Subjects With New Infection

End point description

New infection was defined as a subject 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. Subjects 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). The mITT population was defined as all subjects who had received at least 1 dose of study drug and who had microbiological confirmation of Candida infection.

End point type

Secondary

End point timeframe

During 2 week follow-up after EOT (up to 63 days) and during 6 week follow-up after EOT (up to 91 days)

End point values	Anidulafungin:Subjects Aged 1 month to less than(<)2 Years	Anidulafungin: Subjects Aged 2 to <5 Years	Anidulafungin: Subjects Aged 5 to <18 Years
Number of subjects analysed	16	18	30
Units: percentage of subjects
number (not applicable)
2 week follow-up	0.0	0.0	0.0
6 week follow-up	0.0	0.0	0.0

No statistical analyses for this end point

Secondary: All-Cause Mortality - Number of Subjects Who Died During Overall Study Treatment Period and Follow-Up Visits

Top of page

End point title

All-Cause Mortality - Number of Subjects Who Died During Overall Study Treatment Period and Follow-Up Visits

End point description

The safety population included all randomized subjects who received at least 1 dose of study medication.

End point type

Secondary

End point 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)

End point values	Anidulafungin:Subjects Aged 1 month to less than(<)2 Years	Anidulafungin: Subjects Aged 2 to <5 Years	Anidulafungin: Subjects Aged 5 to <18 Years
Number of subjects analysed	19	19	30
Units: subjects
overall study treatment period	0	1	4
2 Week FU	0	0	1
6 Week FU	1	1	0

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

Baseline up to 6 weeks after end of treatment (up to 91 days)

Adverse event reporting additional description

Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as non-serious in another, or a subject may have experienced both a serious and non-serious event. Analysis performed on safety population.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

20.1

Reporting group title

Anidulafungin:Subjects Aged 1 month to less than(<)2 Years

Reporting group description

Subjects received Anidulafungin loading dose of 3 milligrams per kg(mg/kg) intravenously(IV) on Day 1 and maintenance dose of 1.5mg/kg, every 24 hours for minimum 10 and maximum 35 days.After >=10 days treatment, subjects with microbiologically confirmed invasive candidiasis/candidemia(ICC) and who fulfilled protocol specified criteria [1)afebrile for >=24 hours, 2)tolerate oral medication, 3)documentation of 2 blood cultures [24 hours apart] negative for Candida, 4)eradication/presumed eradication of Candida from other infection sites,identified at enrollment,5)specific Candida isolate susceptible/presumed susceptible to fluconazole, 6)switched to oral fluconazole if improvement in signs,symptoms of Candida infection] and after >=5 days treatment, subjects without microbiologically confirmed ICC,could switch to oral fluconazole(6-12 mg/kg/day,maximum 800mg/day) upto 49 days.First 6 subjects received second antifungal agent, if required at Investigator’s discretion.

Reporting group title

Anidulafungin: Subjects Aged 5 to <18 Years

Reporting group description

Subjects received Anidulafungin loading dose of 3mg/kg, IV on Day 1 and maintenance dose of 1.5mg/kg, every 24 hours for minimum 10 and maximum 35 days. After >=10 days treatment, subjects with microbiologically confirmed ICC and who fulfilled protocol specified criteria ([1)afebrile for >=24 hours, 2)tolerate oral medication, 3)documentation of 2 blood cultures [24 hours apart] negative for Candida, 4)eradication/presumed eradication of Candida from other infection sites,identified at enrollment,5)specific Candida isolate susceptible/presumed susceptible to fluconazole, 6)switched to oral fluconazole if improvement in signs,symptoms of Candida infection]and after >=5 days treatment, subjects without microbiologically confirmed ICC, could switch to oral fluconazole (6-12 mg/kg/day, maximum 800mg/day) upto 49 days.

Reporting group title

Anidulafungin: Subjects Aged 2 to <5 Years

Reporting group description

Serious adverse events	Anidulafungin:Subjects Aged 1 month to less than(<)2 Years	Anidulafungin: Subjects Aged 5 to <18 Years	Anidulafungin: Subjects Aged 2 to <5 Years
Total subjects affected by serious adverse events
subjects affected / exposed	7 / 19 (36.84%)	13 / 30 (43.33%)	10 / 19 (52.63%)
number of deaths (all causes)	1	5	2
number of deaths resulting from adverse events
Investigations
Aspiration bronchial
subjects affected / exposed	0 / 19 (0.00%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Transaminases increased
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Unintentional medical device removal
subjects affected / exposed	0 / 19 (0.00%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Vascular disorders
Brachiocephalic vein thrombosis
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Nervous system disorders
Haemorrhage intracranial
subjects affected / exposed	0 / 19 (0.00%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1
Seizure
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Febrile neutropenia
subjects affected / exposed	1 / 19 (5.26%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pancytopenia
subjects affected / exposed	1 / 19 (5.26%)	0 / 30 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Coagulopathy
subjects affected / exposed	1 / 19 (5.26%)	0 / 30 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
General physical health deterioration
subjects affected / exposed	0 / 19 (0.00%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
Gastrointestinal disorders
Gastrointestinal haemorrhage
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pancreatic pseudocyst
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Diarrhoea
subjects affected / exposed	1 / 19 (5.26%)	0 / 30 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
Acute respiratory failure
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
Respiratory distress
subjects affected / exposed	0 / 19 (0.00%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Respiratory failure
subjects affected / exposed	0 / 19 (0.00%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Mental status changes
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Infections and infestations
Abdominal sepsis
subjects affected / exposed	1 / 19 (5.26%)	0 / 30 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Device related infection
subjects affected / exposed	0 / 19 (0.00%)	0 / 30 (0.00%)	2 / 19 (10.53%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Herpes zoster
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	1 / 19 (5.26%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Meningitis
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Oral herpes
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pharyngitis streptococcal
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Sepsis
subjects affected / exposed	1 / 19 (5.26%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
Septic shock
subjects affected / exposed	0 / 19 (0.00%)	2 / 30 (6.67%)	1 / 19 (5.26%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 1
Staphylococcal bacteraemia
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	2 / 19 (10.53%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	1 / 19 (5.26%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Catheter site infection
subjects affected / exposed	0 / 19 (0.00%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Escherichia infection
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Lower respiratory tract infection
subjects affected / exposed	1 / 19 (5.26%)	0 / 30 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Streptococcal sepsis
subjects affected / exposed	1 / 19 (5.26%)	0 / 30 (0.00%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	1 / 19 (5.26%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Hypoglycaemia
subjects affected / exposed	0 / 19 (0.00%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Metabolic acidosis
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 0%

Non-serious adverse events	Anidulafungin:Subjects Aged 1 month to less than(<)2 Years	Anidulafungin: Subjects Aged 5 to <18 Years	Anidulafungin: Subjects Aged 2 to <5 Years
Total subjects affected by non serious adverse events
subjects affected / exposed	17 / 19 (89.47%)	30 / 30 (100.00%)	17 / 19 (89.47%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Endometrial neoplasm
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Vascular disorders
Hypertension
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Hypotension
subjects affected / exposed	0 / 19 (0.00%)	3 / 30 (10.00%)	2 / 19 (10.53%)
occurrences all number	0	3	3
Phlebitis
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Poor venous access
subjects affected / exposed	1 / 19 (5.26%)	0 / 30 (0.00%)	0 / 19 (0.00%)
occurrences all number	2	0	0
Shock
subjects affected / exposed	0 / 19 (0.00%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	1
Thrombophlebitis superficial
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Deep vein thrombosis
subjects affected / exposed	1 / 19 (5.26%)	0 / 30 (0.00%)	0 / 19 (0.00%)
occurrences all number	1	0	0
Haemorrhage
subjects affected / exposed	1 / 19 (5.26%)	0 / 30 (0.00%)	0 / 19 (0.00%)
occurrences all number	1	0	0
General disorders and administration site conditions
Catheter site erythema
subjects affected / exposed	0 / 19 (0.00%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	1
Catheter site haematoma
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Catheter site haemorrhage
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Catheter site inflammation
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Catheter site pain
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	1 / 19 (5.26%)
occurrences all number	0	1	1
Catheter site rash
subjects affected / exposed	0 / 19 (0.00%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	1
Catheter site related reaction
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Chest pain
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	1 / 19 (5.26%)
occurrences all number	0	1	1
Generalised oedema
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	1 / 19 (5.26%)
occurrences all number	0	1	1
Hyperpyrexia
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Hypothermia
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Infusion site extravasation
subjects affected / exposed	1 / 19 (5.26%)	0 / 30 (0.00%)	0 / 19 (0.00%)
occurrences all number	1	0	0
Malaise
subjects affected / exposed	0 / 19 (0.00%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	1
Pyrexia
subjects affected / exposed	4 / 19 (21.05%)	6 / 30 (20.00%)	3 / 19 (15.79%)
occurrences all number	6	6	4
Face oedema
subjects affected / exposed	1 / 19 (5.26%)	0 / 30 (0.00%)	0 / 19 (0.00%)
occurrences all number	1	0	0
Oedema
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Oedema peripheral
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	1 / 19 (5.26%)
occurrences all number	0	1	1
Pain
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Reproductive system and breast disorders
Genital erythema
subjects affected / exposed	0 / 19 (0.00%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	1
Penile oedema
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Scrotal oedema
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Uterine haematoma
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Vulvovaginal pain
subjects affected / exposed	0 / 19 (0.00%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	1
Respiratory, thoracic and mediastinal disorders
Atelectasis
subjects affected / exposed	1 / 19 (5.26%)	0 / 30 (0.00%)	0 / 19 (0.00%)
occurrences all number	1	0	0
Cough
subjects affected / exposed	0 / 19 (0.00%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	1
Dyspnoea
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Epistaxis
subjects affected / exposed	1 / 19 (5.26%)	5 / 30 (16.67%)	3 / 19 (15.79%)
occurrences all number	1	6	3
Haemoptysis
subjects affected / exposed	1 / 19 (5.26%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences all number	2	0	1
Hypoxia
subjects affected / exposed	0 / 19 (0.00%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	1
Lung disorder
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Oropharyngeal pain
subjects affected / exposed	0 / 19 (0.00%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	1
Pleural effusion
subjects affected / exposed	1 / 19 (5.26%)	0 / 30 (0.00%)	0 / 19 (0.00%)
occurrences all number	1	0	0
Pneumonia aspiration
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Productive cough
subjects affected / exposed	0 / 19 (0.00%)	0 / 30 (0.00%)	2 / 19 (10.53%)
occurrences all number	0	0	2
Respiratory distress
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Rhinalgia
subjects affected / exposed	0 / 19 (0.00%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	1
Rhinorrhoea
subjects affected / exposed	0 / 19 (0.00%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	1
Tachypnoea
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Bronchospasm
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	1 / 19 (5.26%)
occurrences all number	0	1	1
Laryngospasm
subjects affected / exposed	1 / 19 (5.26%)	0 / 30 (0.00%)	0 / 19 (0.00%)
occurrences all number	1	0	0
Respiratory disorder
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Tonsillar erythema
subjects affected / exposed	1 / 19 (5.26%)	0 / 30 (0.00%)	0 / 19 (0.00%)
occurrences all number	2	0	0
Psychiatric disorders
Agitation
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	3 / 19 (15.79%)
occurrences all number	0	1	3
Depression
subjects affected / exposed	0 / 19 (0.00%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	1
Irritability
subjects affected / exposed	1 / 19 (5.26%)	0 / 30 (0.00%)	0 / 19 (0.00%)
occurrences all number	1	0	0
Product issues
Device dislocation
subjects affected / exposed	1 / 19 (5.26%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences all number	1	0	1
Device malfunction
subjects affected / exposed	0 / 19 (0.00%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	2
Investigations
Alanine aminotransferase increased
subjects affected / exposed	2 / 19 (10.53%)	3 / 30 (10.00%)	2 / 19 (10.53%)
occurrences all number	3	3	2
Amylase increased
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Aspartate aminotransferase increased
subjects affected / exposed	2 / 19 (10.53%)	2 / 30 (6.67%)	1 / 19 (5.26%)
occurrences all number	4	2	1
Bacterial test positive
subjects affected / exposed	0 / 19 (0.00%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	1
C-reactive protein increased
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Enterobacter test positive
subjects affected / exposed	0 / 19 (0.00%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	1
Klebsiella test positive
subjects affected / exposed	0 / 19 (0.00%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	1
Liver function test abnormal
subjects affected / exposed	0 / 19 (0.00%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	1
Oxygen saturation decreased
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Platelet count increased
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Prothrombin time prolonged
subjects affected / exposed	0 / 19 (0.00%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	1
Transaminases increased
subjects affected / exposed	1 / 19 (5.26%)	2 / 30 (6.67%)	0 / 19 (0.00%)
occurrences all number	1	2	0
Urine output decreased
subjects affected / exposed	0 / 19 (0.00%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	1
Blood bicarbonate decreased
subjects affected / exposed	1 / 19 (5.26%)	0 / 30 (0.00%)	0 / 19 (0.00%)
occurrences all number	1	0	0
Blood lactate dehydrogenase increased
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Candida test positive
subjects affected / exposed	1 / 19 (5.26%)	0 / 30 (0.00%)	0 / 19 (0.00%)
occurrences all number	2	0	0
Carbon dioxide decreased
subjects affected / exposed	0 / 19 (0.00%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	1
Gamma-glutamyltransferase increased
subjects affected / exposed	1 / 19 (5.26%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	1	1	0
Liver function test increased
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Injury, poisoning and procedural complications
Arthropod bite
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Gastrointestinal stoma complication
subjects affected / exposed	1 / 19 (5.26%)	0 / 30 (0.00%)	0 / 19 (0.00%)
occurrences all number	1	0	0
Accidental overdose
subjects affected / exposed	1 / 19 (5.26%)	0 / 30 (0.00%)	0 / 19 (0.00%)
occurrences all number	1	0	0
Excoriation
subjects affected / exposed	0 / 19 (0.00%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	1
Post procedural haemorrhage
subjects affected / exposed	1 / 19 (5.26%)	0 / 30 (0.00%)	0 / 19 (0.00%)
occurrences all number	1	0	0
Cardiac disorders
Bradycardia
subjects affected / exposed	0 / 19 (0.00%)	2 / 30 (6.67%)	0 / 19 (0.00%)
occurrences all number	0	3	0
Sinus arrhythmia
subjects affected / exposed	0 / 19 (0.00%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	1
Tachycardia
subjects affected / exposed	0 / 19 (0.00%)	2 / 30 (6.67%)	0 / 19 (0.00%)
occurrences all number	0	2	0
Nervous system disorders
Areflexia
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Seizure
subjects affected / exposed	1 / 19 (5.26%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences all number	1	0	2
Headache
subjects affected / exposed	0 / 19 (0.00%)	6 / 30 (20.00%)	1 / 19 (5.26%)
occurrences all number	0	7	2
Loss of consciousness
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Tremor
subjects affected / exposed	0 / 19 (0.00%)	2 / 30 (6.67%)	0 / 19 (0.00%)
occurrences all number	0	2	0
Blood and lymphatic system disorders
Agranulocytosis
subjects affected / exposed	0 / 19 (0.00%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	2
Anaemia
subjects affected / exposed	5 / 19 (26.32%)	1 / 30 (3.33%)	3 / 19 (15.79%)
occurrences all number	9	1	5
Disseminated intravascular coagulation
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Febrile neutropenia
subjects affected / exposed	0 / 19 (0.00%)	2 / 30 (6.67%)	1 / 19 (5.26%)
occurrences all number	0	3	1
Leukopenia
subjects affected / exposed	1 / 19 (5.26%)	1 / 30 (3.33%)	1 / 19 (5.26%)
occurrences all number	1	1	2
Neutropenia
subjects affected / exposed	1 / 19 (5.26%)	3 / 30 (10.00%)	0 / 19 (0.00%)
occurrences all number	1	4	0
Pancytopenia
subjects affected / exposed	1 / 19 (5.26%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences all number	1	0	1
Splenomegaly
subjects affected / exposed	1 / 19 (5.26%)	0 / 30 (0.00%)	0 / 19 (0.00%)
occurrences all number	1	0	0
Thrombocytopenia
subjects affected / exposed	2 / 19 (10.53%)	2 / 30 (6.67%)	1 / 19 (5.26%)
occurrences all number	5	2	2
Thrombocytosis
subjects affected / exposed	1 / 19 (5.26%)	2 / 30 (6.67%)	0 / 19 (0.00%)
occurrences all number	1	2	0
Lymphadenopathy
subjects affected / exposed	0 / 19 (0.00%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	1
Eye disorders
Pupil fixed
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Strabismus
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Eye discharge
subjects affected / exposed	2 / 19 (10.53%)	0 / 30 (0.00%)	0 / 19 (0.00%)
occurrences all number	2	0	0
Eye irritation
subjects affected / exposed	0 / 19 (0.00%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	1
Eyelid oedema
subjects affected / exposed	1 / 19 (5.26%)	0 / 30 (0.00%)	0 / 19 (0.00%)
occurrences all number	1	0	0
Periorbital oedema
subjects affected / exposed	0 / 19 (0.00%)	0 / 30 (0.00%)	2 / 19 (10.53%)
occurrences all number	0	0	2
Gastrointestinal disorders
Abdominal distension
subjects affected / exposed	0 / 19 (0.00%)	3 / 30 (10.00%)	1 / 19 (5.26%)
occurrences all number	0	4	1
Abdominal pain
subjects affected / exposed	0 / 19 (0.00%)	3 / 30 (10.00%)	3 / 19 (15.79%)
occurrences all number	0	3	4
Anorectal discomfort
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Constipation
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Diarrhoea
subjects affected / exposed	3 / 19 (15.79%)	9 / 30 (30.00%)	2 / 19 (10.53%)
occurrences all number	3	12	4
Dry mouth
subjects affected / exposed	0 / 19 (0.00%)	0 / 30 (0.00%)	2 / 19 (10.53%)
occurrences all number	0	0	2
Dysphagia
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Flatulence
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Gastric haemorrhage
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Gastrointestinal motility disorder
subjects affected / exposed	0 / 19 (0.00%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	1
Gastrooesophageal reflux disease
subjects affected / exposed	1 / 19 (5.26%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	1	1	0
Abdominal pain upper
subjects affected / exposed	0 / 19 (0.00%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	1
Haematochezia
subjects affected / exposed	0 / 19 (0.00%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	3
Ileus
subjects affected / exposed	0 / 19 (0.00%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	1
Intra-abdominal haemorrhage
subjects affected / exposed	1 / 19 (5.26%)	0 / 30 (0.00%)	0 / 19 (0.00%)
occurrences all number	1	0	0
Mouth ulceration
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Nausea
subjects affected / exposed	0 / 19 (0.00%)	3 / 30 (10.00%)	1 / 19 (5.26%)
occurrences all number	0	3	1
Pancreatic disorder
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Pancreatic pseudocyst
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Pancreatitis acute
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Saliva altered
subjects affected / exposed	0 / 19 (0.00%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	1
Stomatitis
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	1 / 19 (5.26%)
occurrences all number	0	1	1
Upper gastrointestinal haemorrhage
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Vomiting
subjects affected / exposed	4 / 19 (21.05%)	5 / 30 (16.67%)	7 / 19 (36.84%)
occurrences all number	6	5	17
Food poisoning
subjects affected / exposed	0 / 19 (0.00%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	1
Oral pain
subjects affected / exposed	0 / 19 (0.00%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	1
Salivary hypersecretion
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Hepatobiliary disorders
Hepatitis acute
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Hepatomegaly
subjects affected / exposed	0 / 19 (0.00%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	1
Hyperbilirubinaemia
subjects affected / exposed	0 / 19 (0.00%)	2 / 30 (6.67%)	1 / 19 (5.26%)
occurrences all number	0	2	1
Cholestasis
subjects affected / exposed	1 / 19 (5.26%)	0 / 30 (0.00%)	0 / 19 (0.00%)
occurrences all number	1	0	0
Ocular icterus
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Skin and subcutaneous tissue disorders
Blister
subjects affected / exposed	1 / 19 (5.26%)	0 / 30 (0.00%)	0 / 19 (0.00%)
occurrences all number	1	0	0
Decubitus ulcer
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Dermatitis
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Ecchymosis
subjects affected / exposed	0 / 19 (0.00%)	2 / 30 (6.67%)	0 / 19 (0.00%)
occurrences all number	0	2	0
Erythema
subjects affected / exposed	1 / 19 (5.26%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences all number	1	0	1
Hyperhidrosis
subjects affected / exposed	0 / 19 (0.00%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	1
Livedo reticularis
subjects affected / exposed	0 / 19 (0.00%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	1
Petechiae
subjects affected / exposed	0 / 19 (0.00%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	1
Pruritus generalised
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Rash
subjects affected / exposed	2 / 19 (10.53%)	2 / 30 (6.67%)	2 / 19 (10.53%)
occurrences all number	3	2	2
Rash generalised
subjects affected / exposed	1 / 19 (5.26%)	0 / 30 (0.00%)	0 / 19 (0.00%)
occurrences all number	1	0	0
Rash macular
subjects affected / exposed	0 / 19 (0.00%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	1
Scar pain
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Skin discolouration
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Skin haemorrhage
subjects affected / exposed	0 / 19 (0.00%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	1
Skin hyperpigmentation
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Skin lesion
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Urticaria
subjects affected / exposed	0 / 19 (0.00%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	1
Dermatitis diaper
subjects affected / exposed	1 / 19 (5.26%)	0 / 30 (0.00%)	0 / 19 (0.00%)
occurrences all number	1	0	0
Toxic skin eruption
subjects affected / exposed	1 / 19 (5.26%)	0 / 30 (0.00%)	0 / 19 (0.00%)
occurrences all number	1	0	0
Renal and urinary disorders
Dysuria
subjects affected / exposed	0 / 19 (0.00%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	1
Henoch-Schonlein purpura nephritis
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Acute kidney injury
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Urinary retention
subjects affected / exposed	0 / 19 (0.00%)	2 / 30 (6.67%)	0 / 19 (0.00%)
occurrences all number	0	2	0
Endocrine disorders
Thyroiditis
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	1 / 19 (5.26%)
occurrences all number	0	1	1
Muscular weakness
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Musculoskeletal pain
subjects affected / exposed	0 / 19 (0.00%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	1
Myalgia
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Pain in extremity
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	1 / 19 (5.26%)
occurrences all number	0	1	1
Infections and infestations
Cellulitis
subjects affected / exposed	0 / 19 (0.00%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	1
Clostridium difficile colitis
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Clostridium difficile infection
subjects affected / exposed	0 / 19 (0.00%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	1
Conjunctivitis
subjects affected / exposed	0 / 19 (0.00%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	1
Enterococcal bacteraemia
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Enterococcal sepsis
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Gastroenteritis
subjects affected / exposed	1 / 19 (5.26%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	1	1	0
Herpes virus infection
subjects affected / exposed	0 / 19 (0.00%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	1
Liver abscess
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Lower respiratory tract infection
subjects affected / exposed	0 / 19 (0.00%)	2 / 30 (6.67%)	0 / 19 (0.00%)
occurrences all number	0	2	0
Otitis media acute
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	1 / 19 (5.26%)
occurrences all number	0	1	1
Pneumonia
subjects affected / exposed	0 / 19 (0.00%)	3 / 30 (10.00%)	0 / 19 (0.00%)
occurrences all number	0	3	0
Purulent discharge
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Relapsing fever
subjects affected / exposed	0 / 19 (0.00%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	1
Respiratory tract infection
subjects affected / exposed	1 / 19 (5.26%)	0 / 30 (0.00%)	0 / 19 (0.00%)
occurrences all number	1	0	0
Splenic abscess
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Staphylococcal bacteraemia
subjects affected / exposed	0 / 19 (0.00%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	1
Staphylococcal infection
subjects affected / exposed	0 / 19 (0.00%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	1
Systemic candida
subjects affected / exposed	0 / 19 (0.00%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	1
Tonsillitis
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Upper respiratory tract infection
subjects affected / exposed	1 / 19 (5.26%)	1 / 30 (3.33%)	2 / 19 (10.53%)
occurrences all number	1	1	2
Uterine abscess
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Viral infection
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Viral upper respiratory tract infection
subjects affected / exposed	1 / 19 (5.26%)	0 / 30 (0.00%)	0 / 19 (0.00%)
occurrences all number	1	0	0
Atypical pneumonia
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Bacteraemia
subjects affected / exposed	2 / 19 (10.53%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	2	1	0
Catheter site infection
subjects affected / exposed	0 / 19 (0.00%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	1
Bacterial infection
subjects affected / exposed	1 / 19 (5.26%)	0 / 30 (0.00%)	0 / 19 (0.00%)
occurrences all number	1	0	0
Bronchitis
subjects affected / exposed	1 / 19 (5.26%)	0 / 30 (0.00%)	0 / 19 (0.00%)
occurrences all number	1	0	0
catheter site cellulitis
subjects affected / exposed	1 / 19 (5.26%)	0 / 30 (0.00%)	0 / 19 (0.00%)
occurrences all number	1	0	0
Device related infection
subjects affected / exposed	1 / 19 (5.26%)	0 / 30 (0.00%)	0 / 19 (0.00%)
occurrences all number	1	0	0
Pseudomonas infection
subjects affected / exposed	1 / 19 (5.26%)	0 / 30 (0.00%)	0 / 19 (0.00%)
occurrences all number	1	0	0
Pyelonephritis
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Rash pustular
subjects affected / exposed	1 / 19 (5.26%)	0 / 30 (0.00%)	0 / 19 (0.00%)
occurrences all number	1	0	0
Rhinitis
subjects affected / exposed	1 / 19 (5.26%)	0 / 30 (0.00%)	0 / 19 (0.00%)
occurrences all number	1	0	0
Sepsis
subjects affected / exposed	1 / 19 (5.26%)	0 / 30 (0.00%)	0 / 19 (0.00%)
occurrences all number	1	0	0
Skin infection
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Urinary tract infection bacterial
subjects affected / exposed	0 / 19 (0.00%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	1
Metabolism and nutrition disorders
Acidosis
subjects affected / exposed	0 / 19 (0.00%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	1
Dehydration
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	1 / 19 (5.26%)
occurrences all number	0	1	1
Electrolyte imbalance
subjects affected / exposed	1 / 19 (5.26%)	0 / 30 (0.00%)	0 / 19 (0.00%)
occurrences all number	1	0	0
Hyperglycaemia
subjects affected / exposed	0 / 19 (0.00%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	1
Hypernatraemia
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Hyperuricaemia
subjects affected / exposed	0 / 19 (0.00%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	1
Hypoalbuminaemia
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	0 / 19 (0.00%)
occurrences all number	0	1	0
Hypocalcaemia
subjects affected / exposed	1 / 19 (5.26%)	2 / 30 (6.67%)	1 / 19 (5.26%)
occurrences all number	1	2	1
Hypoglycaemia
subjects affected / exposed	1 / 19 (5.26%)	1 / 30 (3.33%)	2 / 19 (10.53%)
occurrences all number	1	1	2
Hypokalaemia
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	1 / 19 (5.26%)
occurrences all number	0	1	1
Hypomagnesaemia
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	1 / 19 (5.26%)
occurrences all number	0	1	1
Hyponatraemia
subjects affected / exposed	0 / 19 (0.00%)	4 / 30 (13.33%)	0 / 19 (0.00%)
occurrences all number	0	5	0
Hypoproteinaemia
subjects affected / exposed	0 / 19 (0.00%)	1 / 30 (3.33%)	2 / 19 (10.53%)
occurrences all number	0	1	2
Metabolic acidosis
subjects affected / exposed	0 / 19 (0.00%)	0 / 30 (0.00%)	1 / 19 (5.26%)
occurrences all number	0	0	1

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

12 Mar 2008

Exclusion criterion to exclude premature neonates born at gestation of less than 36 weeks (unless the sum of gestational age plus chronological age was at least 44 weeks) was added, as well as a new section on central venous catheter management.

19 Aug 2010

(1)Enrollment of subjects with Candida endocarditis on the basis of at least 1 positive blood culture for Candida spp. and evidence of endocarditis on echocardiogram, and, enrollment of subjects with Candida osteomyelitis on the basis of at least 1 positive culture for Candida spp. from a bone biopsy or aspirate and evidence of osteomyelitis on Magnetic Resonance Imaging (MRI) was allowed; (2) Subjects in the PK subgroup (ie, the first 6 subjects between 1 month and <2 years of age enrolled at selected centers) could be given anidulafungin as either monotherapy or in combination with a second antifungal treatment, at the Investigator’s discretion; (3) Clarified maximum total duration of treatment in the study was 49 days, and the maximum allowed treatment duration with anidulafungin was 35 days; (4) Modified oral fluconazole switch criteria, such that in addition to other criteria currently listed in the protocol, switching to fluconazole could occur if microbiological eradication was presumed based on clinical signs and symptoms, and if susceptibility to fluconazole was presumed based on the Candida species, identified and based on local Candida resistance patterns; (5) Clarified that subjects could have at least 1 clinical criterion present either at the time of study entry or within 96 hours prior to study entry.

08 Dec 2011

At the request of the Korean authorities, the Sponsor removed all aspects of the protocol related to the enrollment of subjects with Candida endocarditis and Candida osteomyelitis; study centers in Korea were not permitted to enroll subjects with these conditions.

07 Jan 2013

The protocol was updated to include: (1) the Sponsor’s recent standard protocol template text, including language regarding females and males of childbearing potential, pregnancy testing and contraception; (2) expected SAEs and additional SAE reporting requirements; (3) medication error reporting requirements and (4) Portugal opted out of enrolling Candida endocarditis and Candida osteomyelitis subjects.

06 Jul 2015

Included measurement of plasma levels of the excipient polysorbate 80, a solubilizing agent contained in the intravenous (IV) formulation of anidulafungin, due to the lack of excipient exposure/response data of polysorbate 80 in very young children (eg, <2 years of age).

16 Sep 2016

(1) Study population was broadened to include children aged 1 month to <2 years only who were at high risk for candidiasis; (2)Amended exclusion criteria, including those related to prior systemic antifungal therapy and removal of prosthetic devices and/or vascular catheters at the suspected site of infection; (3) Added an interim analysis; (4) Reduced the volume of blood required for polysorbate 80 PK samples and added details for preferred sample collection times; (5) Provided instructions for withdrawal of subjects without microbiologically confirmed invasive candidiasis, including ICC.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

Since there was no exposure response relationship, a tabular presentation has not been displayed as in the US Basic Results/ posting because of limitations with the EU posting structure.

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

Clinical Trial Results: A Prospective, Open-Label Study To Assess The Pharmacokinetics, Safety & Efficacy Of Anidulafungin When Used To Treat Children With Invasive Candidiasis, Including Candidemia

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Number of Subjects With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

Primary: Number of Subjects With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

Primary: Number of Subjects with Laboratory Abnormalities

Primary: Number of Subjects with Laboratory Abnormalities

Secondary: Number of Subjects With Global Response

Secondary: Number of Subjects With Global Response

Secondary: Area Under the Plasma Concentration Versus Time Curve From Time Zero to 24 Hours (AUC24) of Anidulafungin for Pharmacokinetic (PK) Subgroup

Secondary: Area Under the Plasma Concentration Versus Time Curve From Time Zero to 24 Hours (AUC24) of Anidulafungin for Pharmacokinetic (PK) Subgroup

Secondary: Maximum Plasma Concentration (Cmax) of Anidulafungin for Pharmacokinetic (PK) Subgroup

Secondary: Maximum Plasma Concentration (Cmax) of Anidulafungin for Pharmacokinetic (PK) Subgroup

Secondary: 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

Secondary: 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

Secondary: Maximum Plasma Concentration (Cmax) of Polysorbate 80 (PS 80) Following Infusion of Anidulafungin for PK Subgroup

Secondary: Maximum Plasma Concentration (Cmax) of Polysorbate 80 (PS 80) Following Infusion of Anidulafungin for PK Subgroup

Secondary: Estimated Area Under the Plasma Curve Over a 24-Hour Dosing Interval at Steady State (AUC0-24ss) of Anidulafungin

Secondary: Estimated Area Under the Plasma Curve Over a 24-Hour Dosing Interval at Steady State (AUC0-24ss) of Anidulafungin

Secondary: Estimated Minimum Plasma Concentration (Cmin) of Anidulafungin

Secondary: Estimated Minimum Plasma Concentration (Cmin) of Anidulafungin

Secondary: Number of Subjects with Greater Than or Equal to 1 Hepatic Adverse Event Categorized on the Basis of Exposure to Anidulafungin (AUC0-24,ss)

Secondary: Number of Subjects with Greater Than or Equal to 1 Hepatic Adverse Event Categorized on the Basis of Exposure to Anidulafungin (AUC0-24,ss)

Secondary: Number of Subjects with Greater Than or Equal to 1 Gastro-Intestinal (GI) Adverse Event Categorized on the Basis of Exposure to Anidulafungin (AUC0-24,ss)

Secondary: Number of Subjects with Greater Than or Equal to 1 Gastro-Intestinal (GI) Adverse Event Categorized on the Basis of Exposure to Anidulafungin (AUC0-24,ss)

Secondary: Percentage of Participants With Global Response Categorized on the Basis of Exposure to Anidulafungin (AUC0-24,ss)

Secondary: Percentage of Participants With Global Response Categorized on the Basis of Exposure to Anidulafungin (AUC0-24,ss)

Secondary: Percentage of Subjects With Relapsed Response

Secondary: Percentage of Subjects With Relapsed Response

Secondary: Percentage of Subjects With New Infection

Secondary: Percentage of Subjects With New Infection

Secondary: All-Cause Mortality - Number of Subjects Who Died During Overall Study Treatment Period and Follow-Up Visits

Secondary: All-Cause Mortality - Number of Subjects Who Died During Overall Study Treatment Period and Follow-Up Visits

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Prospective, Open-Label Study To Assess The Pharmacokinetics, Safety & Efficacy Of Anidulafungin When Used To Treat Children With Invasive Candidiasis, Including Candidemia