An Evaluation Of The Effectiveness And Safety Of Anidulafungin Compared To Caspofungin For The Treatment Of Deep Tissue Infection Due To Candida

• Sponsor: Pfizer (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00805740
• Collaborator: (none)
• Enrollment: 41
• Locations: 18
• Arms: 2
• Duration (Months): 38
• Patients Per Site: 2.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to gather information on the use of anidulafungin for the treatment of serious Candida infection. It is expected that anidulafungin will be at least as safe and as effective as the comparator drug, caspofungin.

Condition or Disease	Intervention/Treatment	Phase
Candidiasis; Fungemia	Drug: Active anidulafungin; Drug: Active Caspofungin	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 41 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Efficacy And Safety Of Eraxis/Ecalta (Anidulafungin) Compared To Cancidas (Caspofungin) In Patients With Candida Deep Tissue Infection
• Study Start Date: Apr 1, 2009
• Actual Primary Completion Date: Jun 1, 2012
• Actual Study Completion Date: Jun 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Anidulafungin arm	Drug: Active anidulafungin; Subjects in this arm will receive active anidulafungin and placebo caspofungin
Experimental: Caspofungin arm	Drug: Active Caspofungin; Subjects in this arm will receive active caspofungin and placebo anidulafungin

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Global Response at End of Treatment (Day 14 To Day 42) [End of Treatment (Day 14 to Day 42)]

   Participants had successful global response if there was clinical response of cure/improvement,microbiological eradication/presumed eradication.Clinical cure:resolution of signs/symptoms (s/s) of Candida infection;no additional systemic/oral antifungal treatment needed.Clinical improvement:significant,but incomplete resolution of s/s of Candida infection;no additional systemic/oral antifungal treatment needed.Microbiological eradication/presumed eradication:baseline pathogen not isolated from original site culture,or culture data not available for participant with successful clinical outcome.

Secondary Outcome Measures

1. Percentage of Participants With Global Response at 2-week and 6-week Follow-up Visit [2-week follow-up (2 weeks after end of treatment [EOT]), 6-week follow-up (6 weeks after EOT)]

   Participants had successful global response if there was clinical response of cure/improvement,microbiological eradication/presumed eradication.Clinical cure:resolution of signs/symptoms (s/s) of Candida infection;no additional systemic/oral antifungal treatment needed.Clinical improvement:significant,but incomplete resolution of s/s of Candida infection;no additional systemic/oral antifungal treatment needed.Microbiological eradication/presumed eradication:baseline pathogen not isolated from original site culture,or culture data not available for participant with successful clinical outcome.

2. Percentage of Participants With Response Based on Clinical Cure and Microbiological Success [EOT (Day 14 to 42), 2-week follow-up (2 weeks after EOT), 6-week follow-up (6 weeks after EOT)]

   A participant had a successful response if there was clinical response of cure and microbiological success (eradication or presumed eradication). Clinical response of cure: resolution of signs and symptoms attributed to Candida infection; no additional systemic or oral antifungal treatment required to complete the course of therapy. Microbiological eradication or presumed eradication: baseline pathogen not isolated from original site culture, or culture data not available for a participant with successful clinical outcome.

3. Percentage of Participants With Clinical Response [Day 10]

   A participant had a successful clinical response if there was clinical response of cure or improvement. Clinical response of cure: resolution of signs and symptoms attributed to Candida infection; no additional systemic or oral antifungal treatment required to complete the course of therapy. Clinical response of improvement: significant, but incomplete resolution of signs and symptoms of Candida infection; no additional systemic or oral antifungal treatment required.

4. Percentage of Participants With Relapse [2-week follow-up (2 weeks after EOT), 6-week follow-up (6 weeks after EOT)]

   Relapse was defined as any baseline Candida sp. isolated following eradication (documented or presumed) or culture data not available for participants with a clinical response of failure after a previous response of success. Prophylactic treatment with oral antifungal agents was not sufficient to document a relapse.

5. Percentage of Participants With New Infection [2-week follow-up (2 weeks after EOT), 6-week follow-up (6 weeks after EOT)]

   New Infection: participant presenting with clinical failure with the emergence of new Candida sp. at the original site of infection or at a distant site of infection. Clinical failure: no significant improvement in signs and symptoms, or death due to Candida infection. Participants must have had received at least 3 doses of study drug to be classified as a failure.

6. Time to Negative Blood Culture [Baseline up to 6-week follow-up (6 weeks after EOT)]

   Negative blood culture referred to absence of Candida sp. in the blood sample of participants who had a positive blood culture at baseline. Time to negative blood culture (days) was calculated as date of first negative blood culture minus first treatment date plus 1.

7. Percentage of Participants With All-cause Mortality [Baseline to EOT (Day 14 to 42), After EOT to 2-week follow-up (2 weeks after EOT), After 2-week follow-up to 6-week follow-up (6 weeks after EOT)]

   All-cause mortality during study therapy and at follow-up visits reported as unique death at EOT, 2 week follow-up and 6 week follow-up.

8. Time to Death [Baseline up to 6-week follow-up (6 weeks after EOT)]

   Time to death (days) was assessed as date of death minus first treatment date plus 1.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 16 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosis of deep tissue Candida infection, defined as growth of Candida sp. from a culture specimen obtained from a normally sterile site accompanied by signs and symptoms of infection.

• Male or female ≥ 16 years of age.

• Expected hospitalization for at least fourteen (14) days.

Exclusion Criteria:

• Pregnancy or breast feeding or planning to become pregnant during the study.

• Recent treatment with one of the study drugs over the last 30 days.

• Allergy to either study drug or to this class of drugs.

• Significant liver dysfunction.

• Suspected Candida osteomyelitis, endocarditis, meningitis or any other infections of the central nervous system.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Newark	Delaware	United States	19713
2	Pfizer Investigational Site	Newark	Delaware	United States	19718
3	Pfizer Investigational Site	Wilmington	Delaware	United States	19801
4	Pfizer Investigational Site	Detroit	Michigan	United States	48202
5	Pfizer Investigational Site	Antwerpen		Belgium	2060
6	Pfizer Investigational Site	Bruxelles		Belgium	1000
7	Pfizer Investigational Site	Bruxelles		Belgium	1070
8	Pfizer Investigational Site	Bruxelles		Belgium	1200
9	Pfizer Investigational Site	Sofia		Bulgaria	1606
10	Pfizer Investigational Site	Vancouver	British Columbia	Canada	V6Z 1Y6
11	Pfizer Investigational Site	Amsterdam		Netherlands	1081 HZ
12	Pfizer Investigational Site	Amsterdam		Netherlands	1091 AC
13	Pfizer Investigational Site	Nijmegen		Netherlands	6532 SZ
14	Pfizer Investigational Site	Coimbra		Portugal	3040-853
15	Pfizer Investigational Site	Lisboa		Portugal	1150-199
16	Pfizer Investigational Site	Bucuresti		Romania	014461
17	Pfizer Investigational Site	P/o Stepanovskoe, Krasnogorskiy District, Moscow Region		Russian Federation	143423
18	Pfizer Investigational Site	Geneve 14		Switzerland	CH-1211

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT00805740
• Other Study ID Numbers: A8851022
• First Posted: Dec 10, 2008
• Last Update Posted: Aug 1, 2013
• Last Verified: May 1, 2013

• Keywords provided by Pfizer: Candidiasis; Invasive Candidiasis; Deep Tissue Candidiasis; Candida; Candidemia; Fungal Infection
• Additional relevant MeSH terms: Infections; Candidiasis; Fungemia; Caspofungin; Anidulafungin

Study Results

Participant Flow

Arm/Group Title	Anidulafungin	Caspofungin
Arm/Group Description	Anidulafungin at a loading dose 200 milligram (mg) as two 100 mg consecutive infusions intravenously over 1.5 hours each, administered prior to or following placebo matched to caspofungin 70 mg infusion intravenously over 1 hour on Day 1. Anidulafungin 100 mg infusion intravenously over 1.5 hours once daily, administered prior to or following placebo matched to caspofungin 50 mg infusion intravenously over 1 hour once daily starting from Day 2 to end of treatment (Day 14 to Day 42).	Caspofungin at a loading dose 70 mg infusion intravenously over 1 hour, administered prior to or following 2 placebo infusions, each matched to anidulafungin 100 mg infusion, intravenously over 1.5 hours each on Day 1. Caspofungin 50 mg infusion intravenously over 1 hour once daily, administered prior to or following placebo matched to anidulafungin 100 mg infusion intravenously over 1.5 hours once daily starting from Day 2 to end of treatment (Day 14 to Day 42).
Period Title: Overall Study
STARTED	28	13
Treated	26	13
COMPLETED	17	9
NOT COMPLETED	11	4

Baseline Characteristics

Arm/Group Title	Anidulafungin	Caspofungin	Total
Arm/Group Description	Anidulafungin at a loading dose 200 milligram (mg) as two 100 mg consecutive infusions intravenously over 1.5 hours each, administered prior to or following placebo matched to caspofungin 70 mg infusion intravenously over 1 hour on Day 1. Anidulafungin 100 mg infusion intravenously over 1.5 hours once daily, administered prior to or following placebo matched to caspofungin 50 mg infusion intravenously over 1 hour once daily starting from Day 2 to end of treatment (Day 14 to Day 42).	Caspofungin at a loading dose 70 mg infusion intravenously over 1 hour, administered prior to or following 2 placebo infusions, each matched to anidulafungin 100 mg infusion, intravenously over 1.5 hours each on Day 1. Caspofungin 50 mg infusion intravenously over 1 hour once daily, administered prior to or following placebo matched to anidulafungin 100 mg infusion intravenously over 1.5 hours once daily starting from Day 2 to end of treatment (Day 14 to Day 42).	Total of all reporting groups
Overall Participants	26	13	39
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.3 (16.2)	63.4 (16.3)	58.6 (16.4)
Sex: Female, Male (Count of Participants)
Female	9 34.6%	5 38.5%	14 35.9%
Male	17 65.4%	8 61.5%	25 64.1%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Global Response at End of Treatment (Day 14 To Day 42)
Description	Participants had successful global response if there was clinical response of cure/improvement,microbiological eradication/presumed eradication.Clinical cure:resolution of signs/symptoms (s/s) of Candida infection;no additional systemic/oral antifungal treatment needed.Clinical improvement:significant,but incomplete resolution of s/s of Candida infection;no additional systemic/oral antifungal treatment needed.Microbiological eradication/presumed eradication:baseline pathogen not isolated from original site culture,or culture data not available for participant with successful clinical outcome.
Time Frame	End of Treatment (Day 14 to Day 42)

Outcome Measure Data

Analysis Population Description

Modified Intent-To-Treat (MITT) population included all participants who received at least 1 dose of study drug and had a positive culture for Candida species (sp.).

Arm/Group Title	Anidulafungin	Caspofungin
Arm/Group Description	Anidulafungin at a loading dose 200 milligram (mg) as two 100 mg consecutive infusions intravenously over 1.5 hours each, administered prior to or following placebo matched to caspofungin 70 mg infusion intravenously over 1 hour on Day 1. Anidulafungin 100 mg infusion intravenously over 1.5 hours once daily, administered prior to or following placebo matched to caspofungin 50 mg infusion intravenously over 1 hour once daily starting from Day 2 to end of treatment (Day 14 to Day 42).	Caspofungin at a loading dose 70 mg infusion intravenously over 1 hour, administered prior to or following 2 placebo infusions, each matched to anidulafungin 100 mg infusion, intravenously over 1.5 hours each on Day 1. Caspofungin 50 mg infusion intravenously over 1 hour once daily, administered prior to or following placebo matched to anidulafungin 100 mg infusion intravenously over 1.5 hours once daily starting from Day 2 to end of treatment (Day 14 to Day 42).
Measure Participants	24	13
Number (95% Confidence Interval) [percentage of participants]	83.3 320.4%	61.5 473.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Anidulafungin, Caspofungin
	Comments	The 95 percent (%) confidence interval (CI) was calculated using method of exact unconditional confidence limits for the difference. Global response (rates of success) by using a 2-sided 95% CI for the true difference in efficacy (Anidulafungin minus Caspofungin) was calculated. Statistical testing was done at 2.5% alpha.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	21.8
	Confidence Interval	(2-Sided) 95%; -12.3 to 53.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percentage of Participants With Global Response at 2-week and 6-week Follow-up Visit
Description	Participants had successful global response if there was clinical response of cure/improvement,microbiological eradication/presumed eradication.Clinical cure:resolution of signs/symptoms (s/s) of Candida infection;no additional systemic/oral antifungal treatment needed.Clinical improvement:significant,but incomplete resolution of s/s of Candida infection;no additional systemic/oral antifungal treatment needed.Microbiological eradication/presumed eradication:baseline pathogen not isolated from original site culture,or culture data not available for participant with successful clinical outcome.
Time Frame	2-week follow-up (2 weeks after end of treatment [EOT]), 6-week follow-up (6 weeks after EOT)

Outcome Measure Data

Analysis Population Description

MITT population included all participants who received at least 1 dose of study drug and had a positive culture for Candida species. Only participants who completed therapy or who had global response of failure at EOT were evaluable for 2- and 6-week follow-up analysis.

Arm/Group Title	Anidulafungin	Caspofungin
Arm/Group Description	Anidulafungin at a loading dose 200 milligram (mg) as two 100 mg consecutive infusions intravenously over 1.5 hours each, administered prior to or following placebo matched to caspofungin 70 mg infusion intravenously over 1 hour on Day 1. Anidulafungin 100 mg infusion intravenously over 1.5 hours once daily, administered prior to or following placebo matched to caspofungin 50 mg infusion intravenously over 1 hour once daily starting from Day 2 to end of treatment (Day 14 to Day 42).	Caspofungin at a loading dose 70 mg infusion intravenously over 1 hour, administered prior to or following 2 placebo infusions, each matched to anidulafungin 100 mg infusion, intravenously over 1.5 hours each on Day 1. Caspofungin 50 mg infusion intravenously over 1 hour once daily, administered prior to or following placebo matched to anidulafungin 100 mg infusion intravenously over 1.5 hours once daily starting from Day 2 to end of treatment (Day 14 to Day 42).
Measure Participants	21	11
2-week follow-up	76.2 293.1%	54.5 419.2%
6-week follow-up	66.7 256.5%	54.5 419.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Anidulafungin, Caspofungin
	Comments	2-week follow-up: The 95% CI was calculated using method of exact unconditional confidence limits for the difference. Global response (rates of success) by using a 2-sided 95% CI for the true difference in efficacy (Anidulafungin minus Caspofungin) was calculated. Statistical testing was done at 2.5% alpha.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	21.6
	Confidence Interval	(2-Sided) 95%; -13.6 to 55.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Anidulafungin, Caspofungin
	Comments	6-week follow-up: The 95% CI was calculated using method of exact unconditional confidence limits for the difference. Global response (rates of success) by using a 2-sided 95% CI for the true difference in efficacy (Anidulafungin minus Caspofungin) was calculated. Statistical testing was done at 2.5% alpha.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	12.1
	Confidence Interval	(2-Sided) 95%; -23.3 to 47.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Percentage of Participants With Response Based on Clinical Cure and Microbiological Success
Description	A participant had a successful response if there was clinical response of cure and microbiological success (eradication or presumed eradication). Clinical response of cure: resolution of signs and symptoms attributed to Candida infection; no additional systemic or oral antifungal treatment required to complete the course of therapy. Microbiological eradication or presumed eradication: baseline pathogen not isolated from original site culture, or culture data not available for a participant with successful clinical outcome.
Time Frame	EOT (Day 14 to 42), 2-week follow-up (2 weeks after EOT), 6-week follow-up (6 weeks after EOT)

Outcome Measure Data

Analysis Population Description

MITT population. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure. Here, 'n' signifies those participants who were evaluable for this measure at given time points for each group respectively.

Arm/Group Title	Anidulafungin	Caspofungin
Arm/Group Description	Anidulafungin at a loading dose 200 milligram (mg) as two 100 mg consecutive infusions intravenously over 1.5 hours each, administered prior to or following placebo matched to caspofungin 70 mg infusion intravenously over 1 hour on Day 1. Anidulafungin 100 mg infusion intravenously over 1.5 hours once daily, administered prior to or following placebo matched to caspofungin 50 mg infusion intravenously over 1 hour once daily starting from Day 2 to end of treatment (Day 14 to Day 42).	Caspofungin at a loading dose 70 mg infusion intravenously over 1 hour, administered prior to or following 2 placebo infusions, each matched to anidulafungin 100 mg infusion, intravenously over 1.5 hours each on Day 1. Caspofungin 50 mg infusion intravenously over 1 hour once daily, administered prior to or following placebo matched to anidulafungin 100 mg infusion intravenously over 1.5 hours once daily starting from Day 2 to end of treatment (Day 14 to Day 42).
Measure Participants	21	8
EOT (n=21,8)	81.0 311.5%	62.5 480.8%
2-week follow-up (n=16,6)	87.5 336.5%	100.0 769.2%
6-week follow-up (n=15,6)	93.3 358.8%	100.0 769.2%

4. Secondary Outcome

Title	Percentage of Participants With Clinical Response
Description	A participant had a successful clinical response if there was clinical response of cure or improvement. Clinical response of cure: resolution of signs and symptoms attributed to Candida infection; no additional systemic or oral antifungal treatment required to complete the course of therapy. Clinical response of improvement: significant, but incomplete resolution of signs and symptoms of Candida infection; no additional systemic or oral antifungal treatment required.
Time Frame	Day 10

Outcome Measure Data

Analysis Population Description

MITT population included all participants who received at least 1 dose of study drug and had a positive culture for Candida species.

Arm/Group Title	Anidulafungin	Caspofungin
Arm/Group Description	Anidulafungin at a loading dose 200 milligram (mg) as two 100 mg consecutive infusions intravenously over 1.5 hours each, administered prior to or following placebo matched to caspofungin 70 mg infusion intravenously over 1 hour on Day 1. Anidulafungin 100 mg infusion intravenously over 1.5 hours once daily, administered prior to or following placebo matched to caspofungin 50 mg infusion intravenously over 1 hour once daily starting from Day 2 to end of treatment (Day 14 to Day 42).	Caspofungin at a loading dose 70 mg infusion intravenously over 1 hour, administered prior to or following 2 placebo infusions, each matched to anidulafungin 100 mg infusion, intravenously over 1.5 hours each on Day 1. Caspofungin 50 mg infusion intravenously over 1 hour once daily, administered prior to or following placebo matched to anidulafungin 100 mg infusion intravenously over 1.5 hours once daily starting from Day 2 to end of treatment (Day 14 to Day 42).
Measure Participants	24	13
Number (95% Confidence Interval) [percentage of participants]	70.8 272.3%	76.9 591.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Anidulafungin, Caspofungin
	Comments	The 95% CI was calculated using method of exact unconditional confidence limits for the difference. Global response (rates of success) by using a 2-sided 95% CI for the true difference in efficacy (Anidulafungin minus Caspofungin) was calculated. Statistical testing was done at 2.5% alpha.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-6.1
	Confidence Interval	(2-Sided) 95%; -39.0 to 27.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Percentage of Participants With Relapse
Description	Relapse was defined as any baseline Candida sp. isolated following eradication (documented or presumed) or culture data not available for participants with a clinical response of failure after a previous response of success. Prophylactic treatment with oral antifungal agents was not sufficient to document a relapse.
Time Frame	2-week follow-up (2 weeks after EOT), 6-week follow-up (6 weeks after EOT)

Outcome Measure Data

Analysis Population Description

MITT population included all participants who received at least 1 dose of study drug and had a positive culture for Candida species.

Arm/Group Title	Anidulafungin	Caspofungin
Arm/Group Description	Anidulafungin at a loading dose 200 milligram (mg) as two 100 mg consecutive infusions intravenously over 1.5 hours each, administered prior to or following placebo matched to caspofungin 70 mg infusion intravenously over 1 hour on Day 1. Anidulafungin 100 mg infusion intravenously over 1.5 hours once daily, administered prior to or following placebo matched to caspofungin 50 mg infusion intravenously over 1 hour once daily starting from Day 2 to end of treatment (Day 14 to Day 42).	Caspofungin at a loading dose 70 mg infusion intravenously over 1 hour, administered prior to or following 2 placebo infusions, each matched to anidulafungin 100 mg infusion, intravenously over 1.5 hours each on Day 1. Caspofungin 50 mg infusion intravenously over 1 hour once daily, administered prior to or following placebo matched to anidulafungin 100 mg infusion intravenously over 1.5 hours once daily starting from Day 2 to end of treatment (Day 14 to Day 42).
Measure Participants	24	13
2-week follow-up	0 0%	0 0%
6-week follow-up	0 0%	0 0%

6. Secondary Outcome

Title	Percentage of Participants With New Infection
Description	New Infection: participant presenting with clinical failure with the emergence of new Candida sp. at the original site of infection or at a distant site of infection. Clinical failure: no significant improvement in signs and symptoms, or death due to Candida infection. Participants must have had received at least 3 doses of study drug to be classified as a failure.
Time Frame	2-week follow-up (2 weeks after EOT), 6-week follow-up (6 weeks after EOT)

Outcome Measure Data

Analysis Population Description

MITT population included all participants who received at least 1 dose of study drug and had a positive culture for Candida species.

Arm/Group Title	Anidulafungin	Caspofungin
Arm/Group Description	Anidulafungin at a loading dose 200 milligram (mg) as two 100 mg consecutive infusions intravenously over 1.5 hours each, administered prior to or following placebo matched to caspofungin 70 mg infusion intravenously over 1 hour on Day 1. Anidulafungin 100 mg infusion intravenously over 1.5 hours once daily, administered prior to or following placebo matched to caspofungin 50 mg infusion intravenously over 1 hour once daily starting from Day 2 to end of treatment (Day 14 to Day 42).	Caspofungin at a loading dose 70 mg infusion intravenously over 1 hour, administered prior to or following 2 placebo infusions, each matched to anidulafungin 100 mg infusion, intravenously over 1.5 hours each on Day 1. Caspofungin 50 mg infusion intravenously over 1 hour once daily, administered prior to or following placebo matched to anidulafungin 100 mg infusion intravenously over 1.5 hours once daily starting from Day 2 to end of treatment (Day 14 to Day 42).
Measure Participants	24	13
2-week follow-up	0 0%	0 0%
6-week follow-up	0 0%	0 0%

7. Secondary Outcome

Title	Time to Negative Blood Culture
Description	Negative blood culture referred to absence of Candida sp. in the blood sample of participants who had a positive blood culture at baseline. Time to negative blood culture (days) was calculated as date of first negative blood culture minus first treatment date plus 1.
Time Frame	Baseline up to 6-week follow-up (6 weeks after EOT)

Outcome Measure Data

Analysis Population Description

A sub-set of MITT population included only those participants who had a positive blood culture for Candida species at baseline.

Arm/Group Title	Anidulafungin	Caspofungin
Arm/Group Description	Anidulafungin at a loading dose 200 milligram (mg) as two 100 mg consecutive infusions intravenously over 1.5 hours each, administered prior to or following placebo matched to caspofungin 70 mg infusion intravenously over 1 hour on Day 1. Anidulafungin 100 mg infusion intravenously over 1.5 hours once daily, administered prior to or following placebo matched to caspofungin 50 mg infusion intravenously over 1 hour once daily starting from Day 2 to end of treatment (Day 14 to Day 42).	Caspofungin at a loading dose 70 mg infusion intravenously over 1 hour, administered prior to or following 2 placebo infusions, each matched to anidulafungin 100 mg infusion, intravenously over 1.5 hours each on Day 1. Caspofungin 50 mg infusion intravenously over 1 hour once daily, administered prior to or following placebo matched to anidulafungin 100 mg infusion intravenously over 1.5 hours once daily starting from Day 2 to end of treatment (Day 14 to Day 42).
Measure Participants	3	4
Median (Full Range) [days]	2.0	3.5

8. Secondary Outcome

Title	Percentage of Participants With All-cause Mortality
Description	All-cause mortality during study therapy and at follow-up visits reported as unique death at EOT, 2 week follow-up and 6 week follow-up.
Time Frame	Baseline to EOT (Day 14 to 42), After EOT to 2-week follow-up (2 weeks after EOT), After 2-week follow-up to 6-week follow-up (6 weeks after EOT)

Outcome Measure Data

Analysis Population Description

Safety analysis set included all randomized participants who received at least 1 dose of study drug.

Arm/Group Title	Anidulafungin	Caspofungin
Arm/Group Description	Anidulafungin at a loading dose 200 milligram (mg) as two 100 mg consecutive infusions intravenously over 1.5 hours each, administered prior to or following placebo matched to caspofungin 70 mg infusion intravenously over 1 hour on Day 1. Anidulafungin 100 mg infusion intravenously over 1.5 hours once daily, administered prior to or following placebo matched to caspofungin 50 mg infusion intravenously over 1 hour once daily starting from Day 2 to end of treatment (Day 14 to Day 42).	Caspofungin at a loading dose 70 mg infusion intravenously over 1 hour, administered prior to or following 2 placebo infusions, each matched to anidulafungin 100 mg infusion, intravenously over 1.5 hours each on Day 1. Caspofungin 50 mg infusion intravenously over 1 hour once daily, administered prior to or following placebo matched to anidulafungin 100 mg infusion intravenously over 1.5 hours once daily starting from Day 2 to end of treatment (Day 14 to Day 42).
Measure Participants	26	13
Baseline to EOT	3.8 14.6%	15.4 118.5%
After EOT to 2-week follow-up	15.4 59.2%	15.4 118.5%
After 2-week follow-up to 6-week follow-up	7.7 29.6%	0.0 0%

9. Secondary Outcome

Title	Time to Death
Description	Time to death (days) was assessed as date of death minus first treatment date plus 1.
Time Frame	Baseline up to 6-week follow-up (6 weeks after EOT)

Outcome Measure Data

Analysis Population Description

Safety analysis set included all randomized participants who received at least 1 dose of study drug.

Arm/Group Title	Anidulafungin	Caspofungin
Arm/Group Description	Anidulafungin at a loading dose 200 milligram (mg) as two 100 mg consecutive infusions intravenously over 1.5 hours each, administered prior to or following placebo matched to caspofungin 70 mg infusion intravenously over 1 hour on Day 1. Anidulafungin 100 mg infusion intravenously over 1.5 hours once daily, administered prior to or following placebo matched to caspofungin 50 mg infusion intravenously over 1 hour once daily starting from Day 2 to end of treatment (Day 14 to Day 42).	Caspofungin at a loading dose 70 mg infusion intravenously over 1 hour, administered prior to or following 2 placebo infusions, each matched to anidulafungin 100 mg infusion, intravenously over 1.5 hours each on Day 1. Caspofungin 50 mg infusion intravenously over 1 hour once daily, administered prior to or following placebo matched to anidulafungin 100 mg infusion intravenously over 1.5 hours once daily starting from Day 2 to end of treatment (Day 14 to Day 42).
Measure Participants	26	13
Median (Full Range) [days]	23.0	11.5

Adverse Events

Adverse Event Reporting Description	The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Arm/Group Title	Anidulafungin		Caspofungin
Arm/Group Description	Anidulafungin at a loading dose 200 milligram (mg) as two 100 mg consecutive infusions intravenously over 1.5 hours each, administered prior to or following placebo matched to caspofungin 70 mg infusion intravenously over 1 hour on Day 1. Anidulafungin 100 mg infusion intravenously over 1.5 hours once daily, administered prior to or following placebo matched to caspofungin 50 mg infusion intravenously over 1 hour once daily starting from Day 2 to end of treatment (Day 14 to Day 42).		Caspofungin at a loading dose 70 mg infusion intravenously over 1 hour, administered prior to or following 2 placebo infusions, each matched to anidulafungin 100 mg infusion, intravenously over 1.5 hours each on Day 1. Caspofungin 50 mg infusion intravenously over 1 hour once daily, administered prior to or following placebo matched to anidulafungin 100 mg infusion intravenously over 1.5 hours once daily starting from Day 2 to end of treatment (Day 14 to Day 42).
All Cause Mortality
	Anidulafungin		Caspofungin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Anidulafungin		Caspofungin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/26 (46.2%)		7/13 (53.8%)
Blood and lymphatic system disorders
Haemorrhagic anaemia	1/26 (3.8%)		0/13 (0%)
Cardiac disorders
Bradycardia	0/26 (0%)		1/13 (7.7%)
Cardiac arrest	0/26 (0%)		2/13 (15.4%)
Gastrointestinal disorders
Abdominal pain	2/26 (7.7%)		0/13 (0%)
Duodenal ulcer	1/26 (3.8%)		0/13 (0%)
Gastrointestinal haemorrhage	1/26 (3.8%)		0/13 (0%)
Intestinal fistula	1/26 (3.8%)		0/13 (0%)
Intra-abdominal haemorrhage	1/26 (3.8%)		0/13 (0%)
General disorders
General physical health deterioration	1/26 (3.8%)		0/13 (0%)
Injury associated with device	1/26 (3.8%)		0/13 (0%)
Multi-organ failure	1/26 (3.8%)		0/13 (0%)
Infections and infestations
Abdominal infection	1/26 (3.8%)		0/13 (0%)
Abdominal sepsis	0/26 (0%)		1/13 (7.7%)
Infectious peritonitis	1/26 (3.8%)		0/13 (0%)
Infectious pleural effusion	1/26 (3.8%)		0/13 (0%)
Nosocomial infection	1/26 (3.8%)		0/13 (0%)
Peptostreptococcus infection	1/26 (3.8%)		0/13 (0%)
Peritonitis	0/26 (0%)		1/13 (7.7%)
Septic shock	1/26 (3.8%)		0/13 (0%)
Tracheobronchitis	1/26 (3.8%)		0/13 (0%)
Injury, poisoning and procedural complications
Splenic haematoma	0/26 (0%)		1/13 (7.7%)
Metabolism and nutrition disorders
Hypoglycaemia	0/26 (0%)		1/13 (7.7%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute leukaemia	1/26 (3.8%)		0/13 (0%)
Nervous system disorders
Hypoxic-ischaemic encephalopathy	0/26 (0%)		1/13 (7.7%)
Renal and urinary disorders
Renal failure acute	0/26 (0%)		1/13 (7.7%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	0/26 (0%)		1/13 (7.7%)
Skin and subcutaneous tissue disorders
Pemphigoid	0/26 (0%)		1/13 (7.7%)
Vascular disorders
Hypotension	1/26 (3.8%)		0/13 (0%)
Other (Not Including Serious) Adverse Events
	Anidulafungin		Caspofungin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	23/26 (88.5%)		11/13 (84.6%)
Blood and lymphatic system disorders
Anaemia	1/26 (3.8%)		3/13 (23.1%)
Coagulopathy	0/26 (0%)		2/13 (15.4%)
Disseminated intravascular coagulation	1/26 (3.8%)		0/13 (0%)
Neutropenia	0/26 (0%)		1/13 (7.7%)
Cardiac disorders
Atrial fibrillation	1/26 (3.8%)		2/13 (15.4%)
Bradycardia	1/26 (3.8%)		0/13 (0%)
Cardiac failure	1/26 (3.8%)		0/13 (0%)
Cardiac failure chronic	0/26 (0%)		1/13 (7.7%)
Sinus tachycardia	0/26 (0%)		1/13 (7.7%)
Tachycardia	2/26 (7.7%)		1/13 (7.7%)
Ventricular tachycardia	1/26 (3.8%)		0/13 (0%)
Eye disorders
Eye disorder	0/26 (0%)		1/13 (7.7%)
Eye haemorrhage	0/26 (0%)		1/13 (7.7%)
Pupils unequal	0/26 (0%)		1/13 (7.7%)
Gastrointestinal disorders
Abdominal pain	1/26 (3.8%)		0/13 (0%)
Constipation	3/26 (11.5%)		1/13 (7.7%)
Diarrhoea	0/26 (0%)		2/13 (15.4%)
Gastric perforation	1/26 (3.8%)		0/13 (0%)
Gastrointestinal haemorrhage	1/26 (3.8%)		0/13 (0%)
Ileus paralytic	1/26 (3.8%)		1/13 (7.7%)
Localised intraabdominal fluid collection	0/26 (0%)		1/13 (7.7%)
Nausea	1/26 (3.8%)		2/13 (15.4%)
Oesophageal ulcer	1/26 (3.8%)		1/13 (7.7%)
Rectal haemorrhage	0/26 (0%)		1/13 (7.7%)
Vomiting	0/26 (0%)		3/13 (23.1%)
General disorders
Chest pain	1/26 (3.8%)		0/13 (0%)
Inflammation	1/26 (3.8%)		0/13 (0%)
Multi-organ failure	1/26 (3.8%)		0/13 (0%)
Oedema	2/26 (7.7%)		1/13 (7.7%)
Oedema peripheral	0/26 (0%)		2/13 (15.4%)
Pyrexia	1/26 (3.8%)		1/13 (7.7%)
Hepatobiliary disorders
Cholestasis	1/26 (3.8%)		0/13 (0%)
Infections and infestations
Abdominal abscess	0/26 (0%)		1/13 (7.7%)
Abdominal wall abscess	0/26 (0%)		1/13 (7.7%)
Abscess	0/26 (0%)		1/13 (7.7%)
Acinetobacter infection	1/26 (3.8%)		0/13 (0%)
Candidiasis	1/26 (3.8%)		0/13 (0%)
Clostridium colitis	0/26 (0%)		1/13 (7.7%)
Cytomegalovirus infection	0/26 (0%)		1/13 (7.7%)
Enterococcal infection	1/26 (3.8%)		0/13 (0%)
Enterococcal sepsis	1/26 (3.8%)		0/13 (0%)
Haematoma infection	1/26 (3.8%)		0/13 (0%)
Peritoneal candidiasis	1/26 (3.8%)		0/13 (0%)
Pneumonia	3/26 (11.5%)		2/13 (15.4%)
Pseudomonal bacteraemia	1/26 (3.8%)		0/13 (0%)
Sepsis	1/26 (3.8%)		0/13 (0%)
Septic shock	1/26 (3.8%)		0/13 (0%)
Skin infection	1/26 (3.8%)		0/13 (0%)
Staphylococcal infection	1/26 (3.8%)		0/13 (0%)
Superinfection bacterial	1/26 (3.8%)		0/13 (0%)
Urinary tract infection	0/26 (0%)		1/13 (7.7%)
Urinary tract infection fungal	1/26 (3.8%)		0/13 (0%)
Injury, poisoning and procedural complications
Open wound	1/26 (3.8%)		0/13 (0%)
Pancreatic leak	1/26 (3.8%)		0/13 (0%)
Pneumothorax traumatic	1/26 (3.8%)		0/13 (0%)
Post procedural haemorrhage	1/26 (3.8%)		1/13 (7.7%)
Procedural pain	1/26 (3.8%)		0/13 (0%)
Suture rupture	1/26 (3.8%)		0/13 (0%)
Weaning failure	1/26 (3.8%)		0/13 (0%)
Wound contamination	1/26 (3.8%)		0/13 (0%)
Investigations
Activated partial thromboplastin time prolonged	0/26 (0%)		1/13 (7.7%)
Alanine aminotransferase increased	0/26 (0%)		1/13 (7.7%)
Aspartate aminotransferase increased	1/26 (3.8%)		1/13 (7.7%)
Aspergillus test positive	1/26 (3.8%)		1/13 (7.7%)
Bacterial test	1/26 (3.8%)		0/13 (0%)
Bacterial test positive	2/26 (7.7%)		1/13 (7.7%)
Bacteroides test positive	0/26 (0%)		1/13 (7.7%)
Blood alkaline phosphatase increased	3/26 (11.5%)		2/13 (15.4%)
Blood bilirubin increased	0/26 (0%)		1/13 (7.7%)
Blood culture negative	1/26 (3.8%)		0/13 (0%)
Blood magnesium decreased	1/26 (3.8%)		0/13 (0%)
Blood potassium decreased	1/26 (3.8%)		2/13 (15.4%)
Blood triglycerides increased	0/26 (0%)		1/13 (7.7%)
C-reactive protein increased	0/26 (0%)		1/13 (7.7%)
Citrobacter test positive	0/26 (0%)		1/13 (7.7%)
Corynebacterium test positive	0/26 (0%)		1/13 (7.7%)
Cytomegalovirus test positive	0/26 (0%)		1/13 (7.7%)
Electrocardiogram QT prolonged	1/26 (3.8%)		0/13 (0%)
Electrocardiogram T wave abnormal	1/26 (3.8%)		0/13 (0%)
Electrocardiogram T wave inversion	0/26 (0%)		1/13 (7.7%)
Enterobacter test positive	1/26 (3.8%)		1/13 (7.7%)
Enterococcus test positive	0/26 (0%)		2/13 (15.4%)
Escherichia test positive	0/26 (0%)		2/13 (15.4%)
Fungal test positive	0/26 (0%)		1/13 (7.7%)
Haematocrit decreased	0/26 (0%)		1/13 (7.7%)
Haemoglobin decreased	2/26 (7.7%)		1/13 (7.7%)
Klebsiella test positive	0/26 (0%)		1/13 (7.7%)
Oxygen saturation decreased	1/26 (3.8%)		0/13 (0%)
Platelet count increased	0/26 (0%)		1/13 (7.7%)
Proteus test positive	0/26 (0%)		1/13 (7.7%)
Prothrombin time prolonged	1/26 (3.8%)		0/13 (0%)
Pseudomonas test positive	1/26 (3.8%)		0/13 (0%)
Staphylococcus test positive	1/26 (3.8%)		3/13 (23.1%)
Stenotrophomonas test positive	1/26 (3.8%)		0/13 (0%)
Streptococcus test positive	1/26 (3.8%)		3/13 (23.1%)
Urine output decreased	0/26 (0%)		1/13 (7.7%)
Weight decreased	2/26 (7.7%)		0/13 (0%)
Metabolism and nutrition disorders
Hypercalcaemia	1/26 (3.8%)		0/13 (0%)
Hyperkalaemia	0/26 (0%)		1/13 (7.7%)
Hypernatraemia	0/26 (0%)		1/13 (7.7%)
Hypertriglyceridaemia	1/26 (3.8%)		0/13 (0%)
Hypoglycaemia	0/26 (0%)		1/13 (7.7%)
Hypokalaemia	1/26 (3.8%)		1/13 (7.7%)
Hyponatraemia	0/26 (0%)		1/13 (7.7%)
Metabolic acidosis	1/26 (3.8%)		1/13 (7.7%)
Metabolic alkalosis	1/26 (3.8%)		1/13 (7.7%)
Musculoskeletal and connective tissue disorders
Fistula	1/26 (3.8%)		0/13 (0%)
Groin pain	0/26 (0%)		1/13 (7.7%)
Muscle haemorrhage	0/26 (0%)		1/13 (7.7%)
Muscle spasms	1/26 (3.8%)		0/13 (0%)
Myalgia	1/26 (3.8%)		0/13 (0%)
Nervous system disorders
Dyskinesia	1/26 (3.8%)		0/13 (0%)
Headache	2/26 (7.7%)		0/13 (0%)
Nervous system disorder	1/26 (3.8%)		0/13 (0%)
Psychiatric disorders
Anxiety	1/26 (3.8%)		1/13 (7.7%)
Catatonia	0/26 (0%)		1/13 (7.7%)
Confusional state	1/26 (3.8%)		1/13 (7.7%)
Delirium	1/26 (3.8%)		1/13 (7.7%)
Depression	2/26 (7.7%)		1/13 (7.7%)
Insomnia	0/26 (0%)		2/13 (15.4%)
Sleep disorder	1/26 (3.8%)		1/13 (7.7%)
Renal and urinary disorders
Hydronephrosis	1/26 (3.8%)		0/13 (0%)
Pollakiuria	1/26 (3.8%)		0/13 (0%)
Renal failure acute	1/26 (3.8%)		0/13 (0%)
Urinoma	0/26 (0%)		1/13 (7.7%)
Respiratory, thoracic and mediastinal disorders
Bronchospasm	1/26 (3.8%)		0/13 (0%)
Chronic obstructive pulmonary disease	0/26 (0%)		1/13 (7.7%)
Dyspnoea	1/26 (3.8%)		1/13 (7.7%)
Hyperventilation	0/26 (0%)		1/13 (7.7%)
Laryngeal oedema	0/26 (0%)		1/13 (7.7%)
Pleural effusion	1/26 (3.8%)		4/13 (30.8%)
Pulmonary embolism	0/26 (0%)		1/13 (7.7%)
Pulmonary oedema	1/26 (3.8%)		0/13 (0%)
Respiratory alkalosis	0/26 (0%)		2/13 (15.4%)
Respiratory failure	2/26 (7.7%)		1/13 (7.7%)
Sputum increased	1/26 (3.8%)		0/13 (0%)
Tachypnoea	0/26 (0%)		1/13 (7.7%)
Wheezing	1/26 (3.8%)		1/13 (7.7%)
Skin and subcutaneous tissue disorders
Decubitus ulcer	1/26 (3.8%)		0/13 (0%)
Dry skin	1/26 (3.8%)		0/13 (0%)
Night sweats	1/26 (3.8%)		0/13 (0%)
Rash	0/26 (0%)		2/13 (15.4%)
Skin necrosis	0/26 (0%)		1/13 (7.7%)
Vascular disorders
Deep vein thrombosis	0/26 (0%)		1/13 (7.7%)
Haematoma	1/26 (3.8%)		0/13 (0%)
Haemodynamic instability	0/26 (0%)		1/13 (7.7%)
Hypertension	4/26 (15.4%)		2/13 (15.4%)
Hypotension	3/26 (11.5%)		3/13 (23.1%)
Jugular vein thrombosis	1/26 (3.8%)		0/13 (0%)
Phlebitis	2/26 (7.7%)		2/13 (15.4%)
Shock	1/26 (3.8%)		1/13 (7.7%)

Limitations/Caveats

The study was prematurely terminated due to slow enrollment. The study was not terminated due to any safety issues or concerns.

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.