An Evaluation Of The Effectiveness And Safety Of Anidulafungin Compared To Caspofungin For The Treatment Of Serious Fungal Infection Due To Candida In Patients With A Dysfunctional Immune System
Sponsor
Pfizer (Industry)
Overall Status
Terminated
CT.gov ID
NCT00806351
Collaborator
(none)
21
10
2
26
2.1
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 Candida infection in patients with an abnormal immune system. 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 |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
21 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 Neutropenic Patients With Invasive Candida Infection
Study Start Date
:
Aug 1, 2009
Actual Primary Completion Date
:
Oct 1, 2011
Actual Study Completion Date
:
Oct 1, 2011
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Anidulafungin Arm Subjects were randomized 2:1 (anidulafungin:caspofunin). |
Drug: Active Anidulafungin
Subjects in this arm will receive active anidulafungin and placebo caspofungin
|
| Experimental: Caspofungin Arm Subjects were randomized 2:1 (anidulafungin:caspofunin). |
Drug: Active Caspofungin
Subjects in this arm will receive active caspofungin and placebo anidulafungin
|
Outcome Measures
Primary Outcome Measures
- Global Response at End of Intravenous Treatment (EOIVT) [Day 10 up to Day 42]
Participant counts of global response of success, failure, or indeterminate. Success: clinical response of cure (no signs, symptoms [s/s] of Candida) or improvement (significant, incomplete resolution of s/s) and microbiological response of eradication (follow-up [f/u] culture negative) or presumed eradication (f/u culture not available and clinical success). Failure: clinical response of failure (greater than or equal to [≥3] doses study medication and no significant improvement of s/s or death due to Candida) and/or unsuccessful microbiological response of persistent(positive culture any Candida species [sp]), new infection or relapse at f/u. Indeterminate: clinical and/or microbiological response of indeterminate (evaluation could not be made due to withdrawal from study prior to assessment of cure or failure) and there was neither clinical response of failure nor unsuccessful microbiological response (persistence or new infection or relapse).
Secondary Outcome Measures
- Global Response at End of Treatment (EOT) [Day 14 up to Day 56]
Participant counts of global response of success, failure, or indeterminate. Success: clinical response of cure (no s/s of Candida) or improvement (significant, incomplete resolution of s/s) and microbiological response of eradication (f/u culture negative) or presumed eradication (f/u culture not available and clinical success). Failure: clinical response of failure (≥3 doses study medication and no significant improvement of s/s or death due to Candida) and/or unsuccessful microbiological response of persistent (positive culture any Candida sp), new infection or relapse at f/u. Indeterminate: clinical and/or microbiological response of indeterminate (evaluation could not be made due to withdrawal from study prior to assessment of cure or failure) and there was neither clinical response of failure nor unsuccessful microbiological response (persistence or new infection or relapse).
- Global Response at 2-Week Follow-Up Visit [2 weeks post treatment]
Participant counts of global response of success, failure, or indeterminate. Success: clinical response of cure (no s/s of Candida) or improvement (significant, incomplete resolution of s/s) and microbiological response of eradication (f/u culture negative) or presumed eradication (f/u culture not available and clinical success). Failure: clinical response of failure (≥3 doses study medication and no significant improvement of s/s or death due to Candida) and/or unsuccessful microbiological response of persistent (positive culture any Candida sp), new infection or relapse at f/u. Indeterminate: clinical and/or microbiological response of indeterminate (evaluation could not be made due to withdrawal from study prior to assessment of cure or failure) and there was neither clinical response of failure nor unsuccessful microbiological response (persistence or new infection or relapse).
- Global Response at 6-Week Follow-Up Visit [6 weeks post treatment]
Participant counts of global response of success, failure, or indeterminate. Success: clinical response of cure (no s/s of Candida) or improvement (significant, incomplete resolution of s/s) and microbiological response of eradication (f/u culture negative) or presumed eradication (f/u culture not available and clinical success). Failure: clinical response of failure (≥3 doses study medication and no significant improvement of s/s or death due to Candida) and/or unsuccessful microbiological response of persistent (positive culture any Candida sp), new infection or relapse at f/u. Indeterminate: clinical and/or microbiological response of indeterminate (evaluation could not be made due to withdrawal from study prior to assessment of cure or failure) and there was neither clinical response of failure nor unsuccessful microbiological response (persistence or new infection or relapse).
- Response Based on Clinical Cure and Microbiological Success at EOIVT [Day 10 up to Day 42]
Participant counts of clinical cure (no s/s of Candida) and microbiological success (eradication [f/u culture negative] or presumed eradication [f/u culture not available and a clinical response of cure]).
- Response Based on Clinical Cure and Microbiological Success at EOT [Day 14 up to Day 56]
Participant counts of clinical cure (no s/s of Candida) and microbiological success (eradication [f/u culture negative] or presumed eradication [f/u culture not available and a clinical response of cure]).
- Response Based on Clinical Cure and Microbiological Success at 2-Week Follow-Up Visit [2 weeks post treatment]
Participant counts of clinical cure (no s/s of Candida) and microbiological success (eradication [f/u culture negative] or presumed eradication [f/u culture not available and a clinical response of cure]).
- Response Based on Clinical Cure and Microbiological Success at 6-Week Follow-Up Visit [6 weeks post treatment]
Participant counts of clinical cure (no s/s of Candida) and microbiological success (eradication [f/u culture negative] or presumed eradication [f/u culture not available and a clinical response of cure]).
- Clinical Response at Day 10 [Day 10]
Participant counts of clinical response categorized as success, failure, or indeterminate. Success: no s/s of Candida (cure) or significant but incomplete resolution of s/s of Candida; no additional systemic or oral antifungal treatment required (improvement). Failure: worsening of s/s of the Candida infection. Indeterminate: evaluation could not be made due to withdrawal from study prior to assessment of cure or failure. Participants who received fewer than 3 doses of study medication were assigned a clinical efficacy response of indeterminate.
- Number of Participants With Recurrence [2 and 6 weeks post treatment]
Participant counts of microbiologic response of recurrence defined as any baseline Candida sp isolated following eradication, or culture data were not available for participants with a clinical response of failure after a previous response of success. Clinical failure defined as ≥3 doses study medication and no significant improvement of s/s or death due to Candida. Clinical success is resolution of s/s and no additional antifungal treatment needed.
- Number of Participants With New Infections [2 and 6 weeks post treatment]
Participant counts of microbiologic response of new infection defined as clinical failure with emergence of new Candida sp not identified at baseline at the original site of infection or at a distant site of infection. Clinical failure defined as ≥3 doses study medication and no significant improvement of s/s or death due to Candida.
- Time to First Negative Blood Culture for Candida Species [Baseline up to Day 56]
A participant had a negative blood culture, if having determined the day of the first negative blood culture, the subsequent blood culture was also negative, or if positive, the interval between the cultures was at least 2 days. For participants whose blood culture went from positive to negative, the time to negative blood culture defined as: date of first negative blood culture minus first treatment date plus 1.
- Time to Death [Day 1 up to Day 98]
Time to death defined as: date of death minus first treatment date plus 1.
- All-Cause Mortality [Baseline up to 6 weeks post treatment]
All-cause mortality during study therapy and at follow-up visits reported as unique deaths at EOIVT, end of oral treatment (EOT-oral), 2 Week Follow-Up and 6 Week Follow-Up
Eligibility Criteria
Criteria
Ages Eligible for Study:
16 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Dysfunctional immune system (reduced neutrophils).
-
Confirmed Candida infection, defined as growth of Candida from a normally sterile site accompanied by signs and symptoms of infection.
-
Male of female ≥16 years of age.
-
Expected hospitalization for at least ten (10) 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 | Sarajevo | Bosnia and Herzegovina | 71000 | |
| 2 | Pfizer Investigational Site | GRENOBLE Cedex 09 | France | 38043 | |
| 3 | Pfizer Investigational Site | Strasbourg Cedex | France | 67098 | |
| 4 | Pfizer Investigational Site | Bologna | Italy | 40138 | |
| 5 | Pfizer Investigational Site | Roma | Italy | 00133 | |
| 6 | Pfizer Investigational Site | Gdansk | Poland | 80-952 | |
| 7 | Pfizer Investigational Site | Warszawa | Poland | 02-776 | |
| 8 | Pfizer Investigational Site | Wroclaw | Poland | 50-367 | |
| 9 | Pfizer Investigational Site | Moscow | Russian Federation | 115478 | |
| 10 | Pfizer Investigational Site | Kosice | Slovakia | 04190 |
Sponsors and Collaborators
- Pfizer
Investigators
- Study Director: Pfizer CT.gov Call Center, Pfizer
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT00806351
Other Study ID Numbers:
- A8851021
First Posted:
Dec 10, 2008
Last Update Posted:
Dec 20, 2012
Last Verified:
Nov 1, 2012
Keywords provided by Pfizer
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Anidulafungin | Caspofungin |
|---|---|---|
| Arm/Group Description | Participants received anidulafungin (100 milligrams [mg]) followed by matched placebo-caspofungin once daily (QD) or participants received matched placebo-caspofungin followed by active anidulafungin (100 mg) QD. Anidulafungin loading dose on Day 1 was 200 mg. Study treatments given either entirely as intravenous (IV) therapy or if protocol-specified criteria met, as sequential IV (at least 10 days) then oral antifungal therapy (14 days). Dosage of antifungal therapy (fluconazole or voriconazole tablets) determined by the Investigator. A maximum of 42 days of IV study treatment and a maximum of 14 days of oral study treatment allowed. Thus, participants may have received up to a maximum of 56 days of study therapy. | Participants received caspofungin (35, 50, or 70 mg depending on participant's weight, baseline liver function, or receipt of an interacting drug) followed by matched placebo-anidulafungin QD or participants received matched placebo-anidulafungin followed by active caspofungin (35, 50, or 70 mg) QD. Caspofungin loading dose on Day 1 was 70 mg. Study treatments given either entirely as IV therapy or if protocol-specified criteria met, as sequential IV (at least 10 days) then oral antifungal therapy (14 days). Dosage of antifungal therapy (fluconazole or voriconazole tablets) determined by the Investigator. A maximum of 42 days of IV study treatment and a maximum of 14 days of oral study treatment allowed. Thus, participants may have received up to a maximum of 56 days of study therapy. |
| Period Title: Overall Study | ||
| STARTED | 15 | 6 |
| COMPLETED | 10 | 2 |
| NOT COMPLETED | 5 | 4 |
Baseline Characteristics
| Arm/Group Title | Anidulafungin | Caspofungin | Total |
|---|---|---|---|
| Arm/Group Description | Participants received anidulafungin (100 milligrams [mg]) followed by matched placebo-caspofungin once daily (QD) or participants received matched placebo-caspofungin followed by active anidulafungin (100 mg) QD. Anidulafungin loading dose on Day 1 was 200 mg. Study treatments given either entirely as intravenous (IV) therapy or if protocol-specified criteria met, as sequential IV (at least 10 days) then oral antifungal therapy (14 days). Dosage of antifungal therapy (fluconazole or voriconazole tablets) determined by the Investigator. A maximum of 42 days of IV study treatment and a maximum of 14 days of oral study treatment allowed. Thus, participants may have received up to a maximum of 56 days of study therapy. | Participants received caspofungin (35, 50, or 70 mg depending on participant's weight, baseline liver function, or receipt of an interacting drug) followed by matched placebo-anidulafungin QD or participants received matched placebo-anidulafungin followed by active caspofungin (35, 50, or 70 mg) QD. Caspofungin loading dose on Day 1 was 70 mg. Study treatments given either entirely as IV therapy or if protocol-specified criteria met, as sequential IV (at least 10 days) then oral antifungal therapy (14 days). Dosage of antifungal therapy (fluconazole or voriconazole tablets) determined by the Investigator. A maximum of 42 days of IV study treatment and a maximum of 14 days of oral study treatment allowed. Thus, participants may have received up to a maximum of 56 days of study therapy. | Total of all reporting groups |
| Overall Participants | 15 | 6 | 21 |
| Age, Customized (participants) [Number] | |||
| 18 to 44 years |
2
13.3%
|
2
33.3%
|
4
19%
|
| 45 to 64 years |
9
60%
|
2
33.3%
|
11
52.4%
|
| greater than or equal to (≥) 65 years |
4
26.7%
|
2
33.3%
|
6
28.6%
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
6
40%
|
3
50%
|
9
42.9%
|
| Male |
9
60%
|
3
50%
|
12
57.1%
|
Outcome Measures
| Title | Global Response at End of Intravenous Treatment (EOIVT) |
|---|---|
| Description | Participant counts of global response of success, failure, or indeterminate. Success: clinical response of cure (no signs, symptoms [s/s] of Candida) or improvement (significant, incomplete resolution of s/s) and microbiological response of eradication (follow-up [f/u] culture negative) or presumed eradication (f/u culture not available and clinical success). Failure: clinical response of failure (greater than or equal to [≥3] doses study medication and no significant improvement of s/s or death due to Candida) and/or unsuccessful microbiological response of persistent(positive culture any Candida species [sp]), new infection or relapse at f/u. Indeterminate: clinical and/or microbiological response of indeterminate (evaluation could not be made due to withdrawal from study prior to assessment of cure or failure) and there was neither clinical response of failure nor unsuccessful microbiological response (persistence or new infection or relapse). |
| Time Frame | Day 10 up to Day 42 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Modified Intent to Treat (MITT) Population: participants who received at least 1 dose of study medication and had positive culture for Candida sp isolated from cultures obtained from a normally sterile site within 96 hours prior to treatment initiation. A global response of failure at EOIVT was carried forward programmatically to subsequent visits. |
| Arm/Group Title | Anidulafungin | Caspofungin |
|---|---|---|
| Arm/Group Description | Participants received anidulafungin (100 milligrams [mg]) followed by matched placebo-caspofungin once daily (QD) or participants received matched placebo-caspofungin followed by active anidulafungin (100 mg) QD. Anidulafungin loading dose on Day 1 was 200 mg. Study treatments given either entirely as intravenous (IV) therapy or if protocol-specified criteria met, as sequential IV (at least 10 days) then oral antifungal therapy (14 days). Dosage of antifungal therapy (fluconazole or voriconazole tablets) determined by the Investigator. A maximum of 42 days of IV study treatment and a maximum of 14 days of oral study treatment allowed. Thus, participants may have received up to a maximum of 56 days of study therapy. | Participants received caspofungin (35, 50, or 70 mg depending on participant's weight, baseline liver function, or receipt of an interacting drug) followed by matched placebo-anidulafungin QD or participants received matched placebo-anidulafungin followed by active caspofungin (35, 50, or 70 mg) QD. Caspofungin loading dose on Day 1 was 70 mg. Study treatments given either entirely as IV therapy or if protocol-specified criteria met, as sequential IV (at least 10 days) then oral antifungal therapy (14 days). Dosage of antifungal therapy (fluconazole or voriconazole tablets) determined by the Investigator. A maximum of 42 days of IV study treatment and a maximum of 14 days of oral study treatment allowed. Thus, participants may have received up to a maximum of 56 days of study therapy. |
| Measure Participants | 11 | 3 |
| Success |
8
53.3%
|
3
50%
|
| Failure |
3
20%
|
0
0%
|
| Indeterminate |
0
0%
|
0
0%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Anidulafungin, Caspofungin |
|---|---|---|
| Comments | The 95 percent confidence interval (95% CI) was calculated using the 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 |
| Estimated Value | -27.3 | |
| Confidence Interval |
(2-Sided) 95% -80.9 to 40.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Global Response at End of Treatment (EOT) |
|---|---|
| Description | Participant counts of global response of success, failure, or indeterminate. Success: clinical response of cure (no s/s of Candida) or improvement (significant, incomplete resolution of s/s) and microbiological response of eradication (f/u culture negative) or presumed eradication (f/u culture not available and clinical success). Failure: clinical response of failure (≥3 doses study medication and no significant improvement of s/s or death due to Candida) and/or unsuccessful microbiological response of persistent (positive culture any Candida sp), new infection or relapse at f/u. Indeterminate: clinical and/or microbiological response of indeterminate (evaluation could not be made due to withdrawal from study prior to assessment of cure or failure) and there was neither clinical response of failure nor unsuccessful microbiological response (persistence or new infection or relapse). |
| Time Frame | Day 14 up to Day 56 |
Outcome Measure Data
| Analysis Population Description |
|---|
| MITT Population; A global response of failure at EOT was carried forward programmatically to all subsequent visits. |
| Arm/Group Title | Anidulafungin | Caspofungin |
|---|---|---|
| Arm/Group Description | Participants received anidulafungin (100 milligrams [mg]) followed by matched placebo-caspofungin once daily (QD) or participants received matched placebo-caspofungin followed by active anidulafungin (100 mg) QD. Anidulafungin loading dose on Day 1 was 200 mg. Study treatments given either entirely as intravenous (IV) therapy or if protocol-specified criteria met, as sequential IV (at least 10 days) then oral antifungal therapy (14 days). Dosage of antifungal therapy (fluconazole or voriconazole tablets) determined by the Investigator. A maximum of 42 days of IV study treatment and a maximum of 14 days of oral study treatment allowed. Thus, participants may have received up to a maximum of 56 days of study therapy. | Participants received caspofungin (35, 50, or 70 mg depending on participant's weight, baseline liver function, or receipt of an interacting drug) followed by matched placebo-anidulafungin QD or participants received matched placebo-anidulafungin followed by active caspofungin (35, 50, or 70 mg) QD. Caspofungin loading dose on Day 1 was 70 mg. Study treatments given either entirely as IV therapy or if protocol-specified criteria met, as sequential IV (at least 10 days) then oral antifungal therapy (14 days). Dosage of antifungal therapy (fluconazole or voriconazole tablets) determined by the Investigator. A maximum of 42 days of IV study treatment and a maximum of 14 days of oral study treatment allowed. Thus, participants may have received up to a maximum of 56 days of study therapy. |
| Measure Participants | 11 | 3 |
| Success |
8
53.3%
|
3
50%
|
| Failure |
3
20%
|
0
0%
|
| Indeterminate |
0
0%
|
0
0%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Anidulafungin, Caspofungin |
|---|---|---|
| Comments | The 95% CI was calculated using the 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 |
| Estimated Value | -27.3 | |
| Confidence Interval |
(2-Sided) 95% -80.9 to 40.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Global Response at 2-Week Follow-Up Visit |
|---|---|
| Description | Participant counts of global response of success, failure, or indeterminate. Success: clinical response of cure (no s/s of Candida) or improvement (significant, incomplete resolution of s/s) and microbiological response of eradication (f/u culture negative) or presumed eradication (f/u culture not available and clinical success). Failure: clinical response of failure (≥3 doses study medication and no significant improvement of s/s or death due to Candida) and/or unsuccessful microbiological response of persistent (positive culture any Candida sp), new infection or relapse at f/u. Indeterminate: clinical and/or microbiological response of indeterminate (evaluation could not be made due to withdrawal from study prior to assessment of cure or failure) and there was neither clinical response of failure nor unsuccessful microbiological response (persistence or new infection or relapse). |
| Time Frame | 2 weeks post treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| MITT Population; subset of participants who, according to the investigator, completed therapy and participants with global response of failure at EOIVT or EOT. A global response of failure at the 2-week and 6-week visits carried forward programmatically to all subsequent visits. Number of participants analyzed (N): participants with evaluable data. |
| Arm/Group Title | Anidulafungin | Caspofungin |
|---|---|---|
| Arm/Group Description | Participants received anidulafungin (100 milligrams [mg]) followed by matched placebo-caspofungin once daily (QD) or participants received matched placebo-caspofungin followed by active anidulafungin (100 mg) QD. Anidulafungin loading dose on Day 1 was 200 mg. Study treatments given either entirely as intravenous (IV) therapy or if protocol-specified criteria met, as sequential IV (at least 10 days) then oral antifungal therapy (14 days). Dosage of antifungal therapy (fluconazole or voriconazole tablets) determined by the Investigator. A maximum of 42 days of IV study treatment and a maximum of 14 days of oral study treatment allowed. Thus, participants may have received up to a maximum of 56 days of study therapy. | Participants received caspofungin (35, 50, or 70 mg depending on participant's weight, baseline liver function, or receipt of an interacting drug) followed by matched placebo-anidulafungin QD or participants received matched placebo-anidulafungin followed by active caspofungin (35, 50, or 70 mg) QD. Caspofungin loading dose on Day 1 was 70 mg. Study treatments given either entirely as IV therapy or if protocol-specified criteria met, as sequential IV (at least 10 days) then oral antifungal therapy (14 days). Dosage of antifungal therapy (fluconazole or voriconazole tablets) determined by the Investigator. A maximum of 42 days of IV study treatment and a maximum of 14 days of oral study treatment allowed. Thus, participants may have received up to a maximum of 56 days of study therapy. |
| Measure Participants | 9 | 1 |
| Success |
6
40%
|
1
16.7%
|
| Failure |
3
20%
|
0
0%
|
| Indeterminate |
0
0%
|
0
0%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Anidulafungin, Caspofungin |
|---|---|---|
| Comments | The 95% CI was calculated using the 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 |
| Estimated Value | -40.0 | |
| Confidence Interval |
(2-Sided) 95% -97.5 to 63.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Global Response at 6-Week Follow-Up Visit |
|---|---|
| Description | Participant counts of global response of success, failure, or indeterminate. Success: clinical response of cure (no s/s of Candida) or improvement (significant, incomplete resolution of s/s) and microbiological response of eradication (f/u culture negative) or presumed eradication (f/u culture not available and clinical success). Failure: clinical response of failure (≥3 doses study medication and no significant improvement of s/s or death due to Candida) and/or unsuccessful microbiological response of persistent (positive culture any Candida sp), new infection or relapse at f/u. Indeterminate: clinical and/or microbiological response of indeterminate (evaluation could not be made due to withdrawal from study prior to assessment of cure or failure) and there was neither clinical response of failure nor unsuccessful microbiological response (persistence or new infection or relapse). |
| Time Frame | 6 weeks post treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| MITT Population; subset of participants who, according to the investigator, completed therapy and participants with global response of failure at EOIVT or EOT. A global response of failure at the 2-week and 6-week visits carried forward programmatically to all subsequent visits. Number of participants analyzed (N): participants with evaluable data. |
| Arm/Group Title | Anidulafungin | Caspofungin |
|---|---|---|
| Arm/Group Description | Participants received anidulafungin (100 milligrams [mg]) followed by matched placebo-caspofungin once daily (QD) or participants received matched placebo-caspofungin followed by active anidulafungin (100 mg) QD. Anidulafungin loading dose on Day 1 was 200 mg. Study treatments given either entirely as intravenous (IV) therapy or if protocol-specified criteria met, as sequential IV (at least 10 days) then oral antifungal therapy (14 days). Dosage of antifungal therapy (fluconazole or voriconazole tablets) determined by the Investigator. A maximum of 42 days of IV study treatment and a maximum of 14 days of oral study treatment allowed. Thus, participants may have received up to a maximum of 56 days of study therapy. | Participants received caspofungin (35, 50, or 70 mg depending on participant's weight, baseline liver function, or receipt of an interacting drug) followed by matched placebo-anidulafungin QD or participants received matched placebo-anidulafungin followed by active caspofungin (35, 50, or 70 mg) QD. Caspofungin loading dose on Day 1 was 70 mg. Study treatments given either entirely as IV therapy or if protocol-specified criteria met, as sequential IV (at least 10 days) then oral antifungal therapy (14 days). Dosage of antifungal therapy (fluconazole or voriconazole tablets) determined by the Investigator. A maximum of 42 days of IV study treatment and a maximum of 14 days of oral study treatment allowed. Thus, participants may have received up to a maximum of 56 days of study therapy. |
| Measure Participants | 9 | 1 |
| Success |
5
33.3%
|
1
16.7%
|
| Failure |
4
26.7%
|
0
0%
|
| Indeterminate |
0
0%
|
0
0%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Anidulafungin, Caspofungin |
|---|---|---|
| Comments | The 95% CI was calculated using the 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 |
| Estimated Value | -50.0 | |
| Confidence Interval |
(2-Sided) 95% -97.5 to 55.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Response Based on Clinical Cure and Microbiological Success at EOIVT |
|---|---|
| Description | Participant counts of clinical cure (no s/s of Candida) and microbiological success (eradication [f/u culture negative] or presumed eradication [f/u culture not available and a clinical response of cure]). |
| Time Frame | Day 10 up to Day 42 |
Outcome Measure Data
| Analysis Population Description |
|---|
| MITT Population; subset of participants with clinical cure or improvement and microbiological eradication or presumed eradication. A global response of failure at EOIVT was carried forward programmatically to all subsequent visits. |
| Arm/Group Title | Anidulafungin | Caspofungin |
|---|---|---|
| Arm/Group Description | Participants received anidulafungin (100 milligrams [mg]) followed by matched placebo-caspofungin once daily (QD) or participants received matched placebo-caspofungin followed by active anidulafungin (100 mg) QD. Anidulafungin loading dose on Day 1 was 200 mg. Study treatments given either entirely as intravenous (IV) therapy or if protocol-specified criteria met, as sequential IV (at least 10 days) then oral antifungal therapy (14 days). Dosage of antifungal therapy (fluconazole or voriconazole tablets) determined by the Investigator. A maximum of 42 days of IV study treatment and a maximum of 14 days of oral study treatment allowed. Thus, participants may have received up to a maximum of 56 days of study therapy. | Participants received caspofungin (35, 50, or 70 mg depending on participant's weight, baseline liver function, or receipt of an interacting drug) followed by matched placebo-anidulafungin QD or participants received matched placebo-anidulafungin followed by active caspofungin (35, 50, or 70 mg) QD. Caspofungin loading dose on Day 1 was 70 mg. Study treatments given either entirely as IV therapy or if protocol-specified criteria met, as sequential IV (at least 10 days) then oral antifungal therapy (14 days). Dosage of antifungal therapy (fluconazole or voriconazole tablets) determined by the Investigator. A maximum of 42 days of IV study treatment and a maximum of 14 days of oral study treatment allowed. Thus, participants may have received up to a maximum of 56 days of study therapy. |
| Measure Participants | 8 | 3 |
| Number [participants] |
7
46.7%
|
2
33.3%
|
| Title | Response Based on Clinical Cure and Microbiological Success at EOT |
|---|---|
| Description | Participant counts of clinical cure (no s/s of Candida) and microbiological success (eradication [f/u culture negative] or presumed eradication [f/u culture not available and a clinical response of cure]). |
| Time Frame | Day 14 up to Day 56 |
Outcome Measure Data
| Analysis Population Description |
|---|
| MITT Population; subset of participants with clinical cure or improvement and microbiological eradication or presumed eradication. A global response of failure at EOT was carried forward programmatically to all subsequent visits. |
| Arm/Group Title | Anidulafungin | Caspofungin |
|---|---|---|
| Arm/Group Description | Participants received anidulafungin (100 milligrams [mg]) followed by matched placebo-caspofungin once daily (QD) or participants received matched placebo-caspofungin followed by active anidulafungin (100 mg) QD. Anidulafungin loading dose on Day 1 was 200 mg. Study treatments given either entirely as intravenous (IV) therapy or if protocol-specified criteria met, as sequential IV (at least 10 days) then oral antifungal therapy (14 days). Dosage of antifungal therapy (fluconazole or voriconazole tablets) determined by the Investigator. A maximum of 42 days of IV study treatment and a maximum of 14 days of oral study treatment allowed. Thus, participants may have received up to a maximum of 56 days of study therapy. | Participants received caspofungin (35, 50, or 70 mg depending on participant's weight, baseline liver function, or receipt of an interacting drug) followed by matched placebo-anidulafungin QD or participants received matched placebo-anidulafungin followed by active caspofungin (35, 50, or 70 mg) QD. Caspofungin loading dose on Day 1 was 70 mg. Study treatments given either entirely as IV therapy or if protocol-specified criteria met, as sequential IV (at least 10 days) then oral antifungal therapy (14 days). Dosage of antifungal therapy (fluconazole or voriconazole tablets) determined by the Investigator. A maximum of 42 days of IV study treatment and a maximum of 14 days of oral study treatment allowed. Thus, participants may have received up to a maximum of 56 days of study therapy. |
| Measure Participants | 8 | 3 |
| Number [participants] |
6
40%
|
3
50%
|
| Title | Response Based on Clinical Cure and Microbiological Success at 2-Week Follow-Up Visit |
|---|---|
| Description | Participant counts of clinical cure (no s/s of Candida) and microbiological success (eradication [f/u culture negative] or presumed eradication [f/u culture not available and a clinical response of cure]). |
| Time Frame | 2 weeks post treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| MITT Population; subset of participants with clinical cure or improvement and microbiological eradication or presumed eradication; Number of participants analyzed (N): participants with evaluable data a specified time point |
| Arm/Group Title | Anidulafungin | Caspofungin |
|---|---|---|
| Arm/Group Description | Participants received anidulafungin (100 milligrams [mg]) followed by matched placebo-caspofungin once daily (QD) or participants received matched placebo-caspofungin followed by active anidulafungin (100 mg) QD. Anidulafungin loading dose on Day 1 was 200 mg. Study treatments given either entirely as intravenous (IV) therapy or if protocol-specified criteria met, as sequential IV (at least 10 days) then oral antifungal therapy (14 days). Dosage of antifungal therapy (fluconazole or voriconazole tablets) determined by the Investigator. A maximum of 42 days of IV study treatment and a maximum of 14 days of oral study treatment allowed. Thus, participants may have received up to a maximum of 56 days of study therapy. | Participants received caspofungin (35, 50, or 70 mg depending on participant's weight, baseline liver function, or receipt of an interacting drug) followed by matched placebo-anidulafungin QD or participants received matched placebo-anidulafungin followed by active caspofungin (35, 50, or 70 mg) QD. Caspofungin loading dose on Day 1 was 70 mg. Study treatments given either entirely as IV therapy or if protocol-specified criteria met, as sequential IV (at least 10 days) then oral antifungal therapy (14 days). Dosage of antifungal therapy (fluconazole or voriconazole tablets) determined by the Investigator. A maximum of 42 days of IV study treatment and a maximum of 14 days of oral study treatment allowed. Thus, participants may have received up to a maximum of 56 days of study therapy. |
| Measure Participants | 6 | 1 |
| Number [participants] |
4
26.7%
|
1
16.7%
|
| Title | Response Based on Clinical Cure and Microbiological Success at 6-Week Follow-Up Visit |
|---|---|
| Description | Participant counts of clinical cure (no s/s of Candida) and microbiological success (eradication [f/u culture negative] or presumed eradication [f/u culture not available and a clinical response of cure]). |
| Time Frame | 6 weeks post treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| MITT Population; subset of participants with clinical cure or improvement and microbiological eradication or presumed eradication; Number of participants analyzed (N): participants with evaluable data a specified time point |
| Arm/Group Title | Anidulafungin | Caspofungin |
|---|---|---|
| Arm/Group Description | Participants received anidulafungin (100 milligrams [mg]) followed by matched placebo-caspofungin once daily (QD) or participants received matched placebo-caspofungin followed by active anidulafungin (100 mg) QD. Anidulafungin loading dose on Day 1 was 200 mg. Study treatments given either entirely as intravenous (IV) therapy or if protocol-specified criteria met, as sequential IV (at least 10 days) then oral antifungal therapy (14 days). Dosage of antifungal therapy (fluconazole or voriconazole tablets) determined by the Investigator. A maximum of 42 days of IV study treatment and a maximum of 14 days of oral study treatment allowed. Thus, participants may have received up to a maximum of 56 days of study therapy. | Participants received caspofungin (35, 50, or 70 mg depending on participant's weight, baseline liver function, or receipt of an interacting drug) followed by matched placebo-anidulafungin QD or participants received matched placebo-anidulafungin followed by active caspofungin (35, 50, or 70 mg) QD. Caspofungin loading dose on Day 1 was 70 mg. Study treatments given either entirely as IV therapy or if protocol-specified criteria met, as sequential IV (at least 10 days) then oral antifungal therapy (14 days). Dosage of antifungal therapy (fluconazole or voriconazole tablets) determined by the Investigator. A maximum of 42 days of IV study treatment and a maximum of 14 days of oral study treatment allowed. Thus, participants may have received up to a maximum of 56 days of study therapy. |
| Measure Participants | 6 | 1 |
| Number [participants] |
6
40%
|
1
16.7%
|
| Title | Clinical Response at Day 10 |
|---|---|
| Description | Participant counts of clinical response categorized as success, failure, or indeterminate. Success: no s/s of Candida (cure) or significant but incomplete resolution of s/s of Candida; no additional systemic or oral antifungal treatment required (improvement). Failure: worsening of s/s of the Candida infection. Indeterminate: evaluation could not be made due to withdrawal from study prior to assessment of cure or failure. Participants who received fewer than 3 doses of study medication were assigned a clinical efficacy response of indeterminate. |
| Time Frame | Day 10 |
Outcome Measure Data
| Analysis Population Description |
|---|
| MITT Population; Number of participants analyzed (N): participants with evaluable data |
| Arm/Group Title | Anidulafungin | Caspofungin |
|---|---|---|
| Arm/Group Description | Participants received anidulafungin (100 milligrams [mg]) followed by matched placebo-caspofungin once daily (QD) or participants received matched placebo-caspofungin followed by active anidulafungin (100 mg) QD. Anidulafungin loading dose on Day 1 was 200 mg. Study treatments given either entirely as intravenous (IV) therapy or if protocol-specified criteria met, as sequential IV (at least 10 days) then oral antifungal therapy (14 days). Dosage of antifungal therapy (fluconazole or voriconazole tablets) determined by the Investigator. A maximum of 42 days of IV study treatment and a maximum of 14 days of oral study treatment allowed. Thus, participants may have received up to a maximum of 56 days of study therapy. | Participants received caspofungin (35, 50, or 70 mg depending on participant's weight, baseline liver function, or receipt of an interacting drug) followed by matched placebo-anidulafungin QD or participants received matched placebo-anidulafungin followed by active caspofungin (35, 50, or 70 mg) QD. Caspofungin loading dose on Day 1 was 70 mg. Study treatments given either entirely as IV therapy or if protocol-specified criteria met, as sequential IV (at least 10 days) then oral antifungal therapy (14 days). Dosage of antifungal therapy (fluconazole or voriconazole tablets) determined by the Investigator. A maximum of 42 days of IV study treatment and a maximum of 14 days of oral study treatment allowed. Thus, participants may have received up to a maximum of 56 days of study therapy. |
| Measure Participants | 9 | 3 |
| Success |
7
46.7%
|
3
50%
|
| Failure |
0
0%
|
0
0%
|
| Indeterminate |
2
13.3%
|
0
0%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Anidulafungin, Caspofungin |
|---|---|---|
| Comments | The 95% CI was calculated using the 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 |
| Estimated Value | -36.4 | |
| Confidence Interval |
(2-Sided) 95% -90.6 to 31.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Number of Participants With Recurrence |
|---|---|
| Description | Participant counts of microbiologic response of recurrence defined as any baseline Candida sp isolated following eradication, or culture data were not available for participants with a clinical response of failure after a previous response of success. Clinical failure defined as ≥3 doses study medication and no significant improvement of s/s or death due to Candida. Clinical success is resolution of s/s and no additional antifungal treatment needed. |
| Time Frame | 2 and 6 weeks post treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| MITT Population |
| Arm/Group Title | Anidulafungin | Caspofungin |
|---|---|---|
| Arm/Group Description | Participants received anidulafungin (100 milligrams [mg]) followed by matched placebo-caspofungin once daily (QD) or participants received matched placebo-caspofungin followed by active anidulafungin (100 mg) QD. Anidulafungin loading dose on Day 1 was 200 mg. Study treatments given either entirely as intravenous (IV) therapy or if protocol-specified criteria met, as sequential IV (at least 10 days) then oral antifungal therapy (14 days). Dosage of antifungal therapy (fluconazole or voriconazole tablets) determined by the Investigator. A maximum of 42 days of IV study treatment and a maximum of 14 days of oral study treatment allowed. Thus, participants may have received up to a maximum of 56 days of study therapy. | Participants received caspofungin (35, 50, or 70 mg depending on participant's weight, baseline liver function, or receipt of an interacting drug) followed by matched placebo-anidulafungin QD or participants received matched placebo-anidulafungin followed by active caspofungin (35, 50, or 70 mg) QD. Caspofungin loading dose on Day 1 was 70 mg. Study treatments given either entirely as IV therapy or if protocol-specified criteria met, as sequential IV (at least 10 days) then oral antifungal therapy (14 days). Dosage of antifungal therapy (fluconazole or voriconazole tablets) determined by the Investigator. A maximum of 42 days of IV study treatment and a maximum of 14 days of oral study treatment allowed. Thus, participants may have received up to a maximum of 56 days of study therapy. |
| Measure Participants | 11 | 3 |
| 2 Weeks post treatment |
0
0%
|
0
0%
|
| 6 Weeks post treatment |
0
0%
|
0
0%
|
| Title | Number of Participants With New Infections |
|---|---|
| Description | Participant counts of microbiologic response of new infection defined as clinical failure with emergence of new Candida sp not identified at baseline at the original site of infection or at a distant site of infection. Clinical failure defined as ≥3 doses study medication and no significant improvement of s/s or death due to Candida. |
| Time Frame | 2 and 6 weeks post treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| MITT Population |
| Arm/Group Title | Anidulafungin | Caspofungin |
|---|---|---|
| Arm/Group Description | Participants received anidulafungin (100 milligrams [mg]) followed by matched placebo-caspofungin once daily (QD) or participants received matched placebo-caspofungin followed by active anidulafungin (100 mg) QD. Anidulafungin loading dose on Day 1 was 200 mg. Study treatments given either entirely as intravenous (IV) therapy or if protocol-specified criteria met, as sequential IV (at least 10 days) then oral antifungal therapy (14 days). Dosage of antifungal therapy (fluconazole or voriconazole tablets) determined by the Investigator. A maximum of 42 days of IV study treatment and a maximum of 14 days of oral study treatment allowed. Thus, participants may have received up to a maximum of 56 days of study therapy. | Participants received caspofungin (35, 50, or 70 mg depending on participant's weight, baseline liver function, or receipt of an interacting drug) followed by matched placebo-anidulafungin QD or participants received matched placebo-anidulafungin followed by active caspofungin (35, 50, or 70 mg) QD. Caspofungin loading dose on Day 1 was 70 mg. Study treatments given either entirely as IV therapy or if protocol-specified criteria met, as sequential IV (at least 10 days) then oral antifungal therapy (14 days). Dosage of antifungal therapy (fluconazole or voriconazole tablets) determined by the Investigator. A maximum of 42 days of IV study treatment and a maximum of 14 days of oral study treatment allowed. Thus, participants may have received up to a maximum of 56 days of study therapy. |
| Measure Participants | 11 | 3 |
| 2 weeks post treatment |
0
0%
|
0
0%
|
| 6 weeks post treatment |
0
0%
|
0
0%
|
| Title | Time to First Negative Blood Culture for Candida Species |
|---|---|
| Description | A participant had a negative blood culture, if having determined the day of the first negative blood culture, the subsequent blood culture was also negative, or if positive, the interval between the cultures was at least 2 days. For participants whose blood culture went from positive to negative, the time to negative blood culture defined as: date of first negative blood culture minus first treatment date plus 1. |
| Time Frame | Baseline up to Day 56 |
Outcome Measure Data
| Analysis Population Description |
|---|
| MITT Population; subset of participants who had a positive blood culture for Candida sp. on Day 1 of treatment. No participant in the Caspofungin treatment arm had a positive blood culture for Candida sp. on Day 1 of treatment. |
| Arm/Group Title | Anidulafungin |
|---|---|
| Arm/Group Description | Participants received anidulafungin (100 milligrams [mg]) followed by matched placebo-caspofungin once daily (QD) or participants received matched placebo-caspofungin followed by active anidulafungin (100 mg) QD. Anidulafungin loading dose on Day 1 was 200 mg. Study treatments given either entirely as intravenous (IV) therapy or if protocol-specified criteria met, as sequential IV (at least 10 days) then oral antifungal therapy (14 days). Dosage of antifungal therapy (fluconazole or voriconazole tablets) determined by the Investigator. A maximum of 42 days of IV study treatment and a maximum of 14 days of oral study treatment allowed. Thus, participants may have received up to a maximum of 56 days of study therapy. |
| Measure Participants | 5 |
| Median (Full Range) [days] |
2.0
|
| Title | Time to Death |
|---|---|
| Description | Time to death defined as: date of death minus first treatment date plus 1. |
| Time Frame | Day 1 up to Day 98 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population;subset of participants who died |
| Arm/Group Title | Anidulafungin | Caspofungin |
|---|---|---|
| Arm/Group Description | Participants received anidulafungin (100 milligrams [mg]) followed by matched placebo-caspofungin once daily (QD) or participants received matched placebo-caspofungin followed by active anidulafungin (100 mg) QD. Anidulafungin loading dose on Day 1 was 200 mg. Study treatments given either entirely as intravenous (IV) therapy or if protocol-specified criteria met, as sequential IV (at least 10 days) then oral antifungal therapy (14 days). Dosage of antifungal therapy (fluconazole or voriconazole tablets) determined by the Investigator. A maximum of 42 days of IV study treatment and a maximum of 14 days of oral study treatment allowed. Thus, participants may have received up to a maximum of 56 days of study therapy. | Participants received caspofungin (35, 50, or 70 mg depending on participant's weight, baseline liver function, or receipt of an interacting drug) followed by matched placebo-anidulafungin QD or participants received matched placebo-anidulafungin followed by active caspofungin (35, 50, or 70 mg) QD. Caspofungin loading dose on Day 1 was 70 mg. Study treatments given either entirely as IV therapy or if protocol-specified criteria met, as sequential IV (at least 10 days) then oral antifungal therapy (14 days). Dosage of antifungal therapy (fluconazole or voriconazole tablets) determined by the Investigator. A maximum of 42 days of IV study treatment and a maximum of 14 days of oral study treatment allowed. Thus, participants may have received up to a maximum of 56 days of study therapy. |
| Measure Participants | 5 | 4 |
| Median (Full Range) [days] |
34.0
|
15.5
|
| Title | All-Cause Mortality |
|---|---|
| Description | All-cause mortality during study therapy and at follow-up visits reported as unique deaths at EOIVT, end of oral treatment (EOT-oral), 2 Week Follow-Up and 6 Week Follow-Up |
| Time Frame | Baseline up to 6 weeks post treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population |
| Arm/Group Title | Anidulafungin | Caspofungin |
|---|---|---|
| Arm/Group Description | Participants received anidulafungin (100 milligrams [mg]) followed by matched placebo-caspofungin once daily (QD) or participants received matched placebo-caspofungin followed by active anidulafungin (100 mg) QD. Anidulafungin loading dose on Day 1 was 200 mg. Study treatments given either entirely as intravenous (IV) therapy or if protocol-specified criteria met, as sequential IV (at least 10 days) then oral antifungal therapy (14 days). Dosage of antifungal therapy (fluconazole or voriconazole tablets) determined by the Investigator. A maximum of 42 days of IV study treatment and a maximum of 14 days of oral study treatment allowed. Thus, participants may have received up to a maximum of 56 days of study therapy. | Participants received caspofungin (35, 50, or 70 mg depending on participant's weight, baseline liver function, or receipt of an interacting drug) followed by matched placebo-anidulafungin QD or participants received matched placebo-anidulafungin followed by active caspofungin (35, 50, or 70 mg) QD. Caspofungin loading dose on Day 1 was 70 mg. Study treatments given either entirely as IV therapy or if protocol-specified criteria met, as sequential IV (at least 10 days) then oral antifungal therapy (14 days). Dosage of antifungal therapy (fluconazole or voriconazole tablets) determined by the Investigator. A maximum of 42 days of IV study treatment and a maximum of 14 days of oral study treatment allowed. Thus, participants may have received up to a maximum of 56 days of study therapy. |
| Measure Participants | 15 | 6 |
| at EOIVT |
1
6.7%
|
1
16.7%
|
| at EOT - oral |
1
6.7%
|
0
0%
|
| at 2 Week Follow-Up Visit |
1
6.7%
|
3
50%
|
| at 6 Week Follow-Up Visit |
2
13.3%
|
0
0%
|
Adverse Events
| Time Frame | ||||
|---|---|---|---|---|
| Adverse Event Reporting Description | All-causality events reported. The same event may appear as both an adverse event (AE) and serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. | |||
| Arm/Group Title | Anidulafungin | Caspofungin | ||
| Arm/Group Description | Participants received anidulafungin (100 milligrams [mg]) followed by matched placebo-caspofungin once daily (QD) or participants received matched placebo-caspofungin followed by active anidulafungin (100 mg) QD. Anidulafungin loading dose on Day 1 was 200 mg. Study treatments given either entirely as intravenous (IV) therapy or if protocol-specified criteria met, as sequential IV (at least 10 days) then oral antifungal therapy (14 days). Dosage of antifungal therapy (fluconazole or voriconazole tablets) determined by the Investigator. A maximum of 42 days of IV study treatment and a maximum of 14 days of oral study treatment allowed. Thus, participants may have received up to a maximum of 56 days of study therapy. | Participants received caspofungin (35, 50, or 70 mg depending on participant's weight, baseline liver function, or receipt of an interacting drug) followed by matched placebo-anidulafungin QD or participants received matched placebo-anidulafungin followed by active caspofungin (35, 50, or 70 mg) QD. Caspofungin loading dose on Day 1 was 70 mg. Study treatments given either entirely as IV therapy or if protocol-specified criteria met, as sequential IV (at least 10 days) then oral antifungal therapy (14 days). Dosage of antifungal therapy (fluconazole or voriconazole tablets) determined by the Investigator. A maximum of 42 days of IV study treatment and a maximum of 14 days of oral study treatment allowed. Thus, participants may have received up to a maximum of 56 days of study therapy. | ||
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 | 5/15 (33.3%) | 4/6 (66.7%) | ||
| General disorders | ||||
| Drug ineffective | 1/15 (6.7%) | 0/6 (0%) | ||
| Multi-organ failure | 0/15 (0%) | 1/6 (16.7%) | ||
| Hepatobiliary disorders | ||||
| hepatotoxicity | 0/15 (0%) | 1/6 (16.7%) | ||
| Infections and infestations | ||||
| Candidiasis | 1/15 (6.7%) | 0/6 (0%) | ||
| Pneumonia | 1/15 (6.7%) | 0/6 (0%) | ||
| Sepsis | 0/15 (0%) | 2/6 (33.3%) | ||
| Septic shock | 0/15 (0%) | 1/6 (16.7%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Acute leukaemia | 1/15 (6.7%) | 0/6 (0%) | ||
| Acute lymphocytic leukaemia | 0/15 (0%) | 1/6 (16.7%) | ||
| Leukaemia | 1/15 (6.7%) | 0/6 (0%) | ||
| Lymphoma | 0/15 (0%) | 1/6 (16.7%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Respiratory distress | 1/15 (6.7%) | 0/6 (0%) | ||
| Respiratory failure | 1/15 (6.7%) | 0/6 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Anidulafungin | Caspofungin | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 14/15 (93.3%) | 5/6 (83.3%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 1/15 (6.7%) | 1/6 (16.7%) | ||
| Lymphadenopathy | 1/15 (6.7%) | 0/6 (0%) | ||
| Lymphopenia | 1/15 (6.7%) | 0/6 (0%) | ||
| Neutropenia | 1/15 (6.7%) | 0/6 (0%) | ||
| Thrombocytopenia | 1/15 (6.7%) | 0/6 (0%) | ||
| Cardiac disorders | ||||
| Atrial fibrillation | 1/15 (6.7%) | 0/6 (0%) | ||
| Bradycardia | 1/15 (6.7%) | 0/6 (0%) | ||
| Supraventricular tachycardia | 1/15 (6.7%) | 0/6 (0%) | ||
| Tachycardia | 1/15 (6.7%) | 0/6 (0%) | ||
| Eye disorders | ||||
| Colour blindness acquired | 0/15 (0%) | 1/6 (16.7%) | ||
| Conjunctivitis | 1/15 (6.7%) | 0/6 (0%) | ||
| Phosphenes | 0/15 (0%) | 1/6 (16.7%) | ||
| Retinal exudates | 1/15 (6.7%) | 0/6 (0%) | ||
| Retinal haemorrhage | 1/15 (6.7%) | 0/6 (0%) | ||
| Visual brightness | 0/15 (0%) | 1/6 (16.7%) | ||
| Gastrointestinal disorders | ||||
| Abdominal distension | 0/15 (0%) | 1/6 (16.7%) | ||
| Abdominal pain | 3/15 (20%) | 0/6 (0%) | ||
| Constipation | 1/15 (6.7%) | 0/6 (0%) | ||
| Diarrhoea | 2/15 (13.3%) | 1/6 (16.7%) | ||
| Dry mouth | 1/15 (6.7%) | 0/6 (0%) | ||
| Dyspepsia | 0/15 (0%) | 1/6 (16.7%) | ||
| Gingival disorder | 1/15 (6.7%) | 0/6 (0%) | ||
| Melaena | 2/15 (13.3%) | 1/6 (16.7%) | ||
| Mouth haemorrhage | 0/15 (0%) | 1/6 (16.7%) | ||
| Nausea | 5/15 (33.3%) | 1/6 (16.7%) | ||
| Stomatitis | 1/15 (6.7%) | 0/6 (0%) | ||
| Vomiting | 0/15 (0%) | 1/6 (16.7%) | ||
| Palatal disorder | 1/15 (6.7%) | 0/6 (0%) | ||
| General disorders | ||||
| Asthenia | 1/15 (6.7%) | 0/6 (0%) | ||
| Catheter site inflammation | 1/15 (6.7%) | 0/6 (0%) | ||
| Chills | 1/15 (6.7%) | 0/6 (0%) | ||
| General physical health deterioration | 1/15 (6.7%) | 0/6 (0%) | ||
| Generalised oedema | 0/15 (0%) | 1/6 (16.7%) | ||
| Malaise | 1/15 (6.7%) | 0/6 (0%) | ||
| Mucosal inflammation | 1/15 (6.7%) | 1/6 (16.7%) | ||
| Oedema peripheral | 2/15 (13.3%) | 0/6 (0%) | ||
| Pain | 0/15 (0%) | 1/6 (16.7%) | ||
| Pyrexia | 6/15 (40%) | 1/6 (16.7%) | ||
| Hepatobiliary disorders | ||||
| Hyperbilirubinaemia | 1/15 (6.7%) | 0/6 (0%) | ||
| Infections and infestations | ||||
| Aspergillosis | 2/15 (13.3%) | 0/6 (0%) | ||
| Bronchopneumonia | 1/15 (6.7%) | 0/6 (0%) | ||
| Enterococcal bacteraemia | 1/15 (6.7%) | 1/6 (16.7%) | ||
| Enterococcal infection | 1/15 (6.7%) | 0/6 (0%) | ||
| Escherichia bacteraemia | 2/15 (13.3%) | 0/6 (0%) | ||
| Furuncle | 1/15 (6.7%) | 0/6 (0%) | ||
| Klebsiella bacteraemia | 1/15 (6.7%) | 0/6 (0%) | ||
| Oral fungal infection | 1/15 (6.7%) | 0/6 (0%) | ||
| Oral herpes | 1/15 (6.7%) | 0/6 (0%) | ||
| Postoperative wound infection | 0/15 (0%) | 1/6 (16.7%) | ||
| Pseudomonas infection | 1/15 (6.7%) | 0/6 (0%) | ||
| Sepsis | 1/15 (6.7%) | 0/6 (0%) | ||
| Staphylococcal bacteraemia | 1/15 (6.7%) | 0/6 (0%) | ||
| Streptococcal bacteraemia | 1/15 (6.7%) | 0/6 (0%) | ||
| Urinary tract infection enterococcal | 0/15 (0%) | 1/6 (16.7%) | ||
| Injury, poisoning and procedural complications | ||||
| Eschar | 1/15 (6.7%) | 0/6 (0%) | ||
| Investigations | ||||
| Alanine aminotransferase increased | 1/15 (6.7%) | 1/6 (16.7%) | ||
| Aspartate aminotransferase increased | 1/15 (6.7%) | 1/6 (16.7%) | ||
| Bacterial test positive | 1/15 (6.7%) | 0/6 (0%) | ||
| Blood alkaline phosphatase increased | 3/15 (20%) | 1/6 (16.7%) | ||
| Blood bilirubin increased | 1/15 (6.7%) | 1/6 (16.7%) | ||
| Blood creatine increased | 1/15 (6.7%) | 0/6 (0%) | ||
| Blood creatinine increased | 1/15 (6.7%) | 1/6 (16.7%) | ||
| Blood lactate dehydrogenase increased | 1/15 (6.7%) | 0/6 (0%) | ||
| Blood urea increased | 1/15 (6.7%) | 0/6 (0%) | ||
| Breath sounds abnormal | 1/15 (6.7%) | 0/6 (0%) | ||
| Fungal test positive | 2/15 (13.3%) | 0/6 (0%) | ||
| Gamma-glutamyltransferase increased | 1/15 (6.7%) | 2/6 (33.3%) | ||
| Weight increased | 1/15 (6.7%) | 0/6 (0%) | ||
| Metabolism and nutrition disorders | ||||
| Hyperkalaemia | 1/15 (6.7%) | 0/6 (0%) | ||
| Hypoalbuminaemia | 2/15 (13.3%) | 0/6 (0%) | ||
| Hypocalcaemia | 1/15 (6.7%) | 0/6 (0%) | ||
| Hypokalaemia | 2/15 (13.3%) | 1/6 (16.7%) | ||
| Hyponatraemia | 1/15 (6.7%) | 0/6 (0%) | ||
| Feeding disorder | 1/15 (6.7%) | 0/6 (0%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Pain in extremity | 1/15 (6.7%) | 0/6 (0%) | ||
| Soft tissue necrosis | 1/15 (6.7%) | 0/6 (0%) | ||
| Nervous system disorders | ||||
| Coma | 0/15 (0%) | 1/6 (16.7%) | ||
| Headache | 2/15 (13.3%) | 0/6 (0%) | ||
| Somnolence | 1/15 (6.7%) | 1/6 (16.7%) | ||
| Tremor | 1/15 (6.7%) | 0/6 (0%) | ||
| Psychiatric disorders | ||||
| Agitation | 0/15 (0%) | 1/6 (16.7%) | ||
| Anxiety | 1/15 (6.7%) | 0/6 (0%) | ||
| Confusional state | 2/15 (13.3%) | 0/6 (0%) | ||
| Insomnia | 1/15 (6.7%) | 0/6 (0%) | ||
| Renal and urinary disorders | ||||
| Anuria | 0/15 (0%) | 1/6 (16.7%) | ||
| Costovertebral angle tenderness | 1/15 (6.7%) | 0/6 (0%) | ||
| Haematuria | 1/15 (6.7%) | 0/6 (0%) | ||
| Renal failure | 1/15 (6.7%) | 0/6 (0%) | ||
| Urinary retention | 1/15 (6.7%) | 0/6 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Acute pulmonary oedema | 1/15 (6.7%) | 0/6 (0%) | ||
| Cough | 2/15 (13.3%) | 0/6 (0%) | ||
| Dyspnoea | 3/15 (20%) | 0/6 (0%) | ||
| Hypoventilation | 1/15 (6.7%) | 0/6 (0%) | ||
| Hypoxia | 1/15 (6.7%) | 0/6 (0%) | ||
| Pleural effusion | 3/15 (20%) | 0/6 (0%) | ||
| Pulmonary congestion | 0/15 (0%) | 1/6 (16.7%) | ||
| Rales | 3/15 (20%) | 1/6 (16.7%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Decubitus ulcer | 1/15 (6.7%) | 0/6 (0%) | ||
| Generalised erythema | 0/15 (0%) | 1/6 (16.7%) | ||
| Papule | 0/15 (0%) | 1/6 (16.7%) | ||
| Pruritus | 0/15 (0%) | 1/6 (16.7%) | ||
| Purpura | 1/15 (6.7%) | 0/6 (0%) | ||
| Rash | 2/15 (13.3%) | 0/6 (0%) | ||
| Rash generalised | 1/15 (6.7%) | 0/6 (0%) | ||
| Rash maculo-papular | 1/15 (6.7%) | 0/6 (0%) | ||
| Toxic skin eruption | 1/15 (6.7%) | 0/6 (0%) | ||
| Vascular disorders | ||||
| Haematoma | 1/15 (6.7%) | 0/6 (0%) | ||
| Hyperaemia | 1/15 (6.7%) | 0/6 (0%) | ||
| Hypotension | 1/15 (6.7%) | 1/6 (16.7%) | ||
Limitations/Caveats
Study prematurely terminated due to slow enrollment, not due to safety issues. Meaningful interpretation and comparison of treatment outcomes with caspofungin was difficult due to low number of participants (n=3) with confirmed Candida infection.
More Information
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.
Results Point of Contact
| Name/Title | Pfizer ClinicalTrials.gov Call Center |
|---|---|
| Organization | Pfizer, Inc. |
| Phone | 1-800-718-1021 |
| ClinicalTrials.gov_Inquiries@pfizer.com |
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT00806351
Other Study ID Numbers:
- A8851021
First Posted:
Dec 10, 2008
Last Update Posted:
Dec 20, 2012
Last Verified:
Nov 1, 2012