Anidulafungin In Treatment Of Candidemia In Asian Subjects

Study Overview
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Brief Summary
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The purpose of this study is to determine whether or not the Investigational Study Drug anidulafungin is safe and effective in the treatment of a fungal infection, candidemia, in Asian subjects.

Official Title
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A Phase IIIB Pilot Study Of Efficacy And Safety Of Anidulafungin In The Treatment Of Candidemia In Asian Patients

Conditions
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Candidemia

Intervention / Treatment
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* Drug: Anidulafungin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with at least one positive blood test for Candida pathogen from a blood sample taken within 96 hours prior to start of study treatment. Subjects with clinical evidence of candida infection within 48 hours prior to enrollment. Acute Physiology and Chronic Health Enquiry (APACHE) score less than or equal to 20. Exclusion Criteria: Prior exposure to systemic antifungals for more than 48 hours. Subjects who had, at any time, previously received anidulafungin. Subjects with poor venous (vein) access that would inhibit the administration of the intravenous study drug or withdrawing of multiple blood samples. Life expectancy < 72 hours.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Open<br>This is an open-label, multi-center, non-comparative 12 week study evaluating the efficacy and safety of anidulafungin in subjects with candidemia. | Drug: Anidulafungin<br>* Eligible subjects will be initiated on a single loading dose of 200 mg IV anidulafungin, followed by 100 mg IV anidulafungin once daily for a minimum of 5 days but not more than 42 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Global Response of Success at End of Treatment | Number of subjects with clinician assessed global response of success; defined as cure (resolution of signs and symptoms of Candida infection) or improvement (significant but incomplete resolution of signs and symptoms of Candida infection) on the clinical response in conjunction with eradication (follow up negative culture result for Candida species [spp]) or presumed eradication (follow up culture was not available and clinical outcome defined as success) on the microbiological response. | End of treatment (EOT) = Day 5 up to Day 42 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Global Response of Success at Endpoints | Number of subjects with clinician assessed global response of success. Defined as cure or improvement (cure/improvement): cure=resolution of signs and symptoms of Candida infection; improvement=significant but incomplete resolution of signs and symptoms of Candida infection on the clinical response in conjunction with eradication or presumed eradication (erad/presumed erad): erad=follow up negative culture result for Candida spp; presumed erad=follow up culture was not available and clinical outcome defined as success on the microbiological response. | End of intravenous treatment (EOIT), end of Week 2 after EOT (2 Wks post EOT), end of Week 6 after EOT (6 Wks post EOT), at end of 12 weeks after baseline (12 Wks post baseline) | 
| Number of Subjects With Clinical Response of Success at Endpoints | Number of subjects with clinician assessed clinical response (CR) of success. Defined as cure or improvement (cure/improvement): cure=resolution of signs and symptoms of Candida infection; improvement=significant but incomplete resolution of signs and symptoms of Candida infection on the clinical response. | EOIT, EOT (Day 5 up to Day 42), 2 Wks post EOT, 6 Wks post EOT, 12 Wks post baseline | 
| Number of Subjects With Microbiological Response of Success at Endpoints | Number of subjects with clinician assessed microbiological response (MR) of success. Defined as eradication or presumed eradication (erad/presumed erad): erad=follow up negative culture result for Candida spp; presumed eradication=follow up culture was not available and clinical outcome defined as success on the microbiological response. | EOIT, EOT (Day 5 up to Day 42), 2 Wks post EOT, 6 Wks post EOT, 12 Wks post baseline | 
| Time to Death From Any Cause | Time to death (median survival time in days) from any cause; time to death includes the first day (Day 1) of study drug (baseline and Day 1 allowed to occur on same day). EOT visit could occur anytime from Day 5 through Day 42; if a subject terminated early, the timeframe at end of 12 weeks after baseline could occur in the follow-up period (6 Wks post EOT or Week 12 post EOT). | Baseline through end of 12 weeks after baseline | 
| Time to Death Due to Candidemia | Time to death (median survival time in days) due to candidemia; time to death includes the first day (Day 1) of study drug (baseline and Day 1 allowed to occur on same day). EOT visit could occur anytime from Day 5 through Day 42; if a subject terminated early, the timeframe at end of 12 weeks after baseline could occur in the follow-up period (6 Wks post EOT or Week 12 post EOT). | Baseline through end of 12 weeks after baseline | 
| Absolute Values for β-D-glucan Assay Results at Endpoints in Relation to Clinical Response Status of Success or Status of Failure at End of All Treatment | Absolute values for β-D-glucan (range 0 to 6000 picograms per milliliter [pg/mL]) summarized at all timeframe endpoints by subject's at end of all treatment clinical response status of success (Success at EOT) or failure (Failure at EOT) and as combined status of all subjects (All at EOT). Success: cure (resolution of signs and symptoms of Candida infection) or improvement (significant but incomplete resolution of signs and symptoms); failure: no significant improvement in signs and symptoms or death due to Candida infection; subjects must have received at least 3 doses of anidulafungin. | Baseline, Day 3, Day 5, Day 7, EOT (Day 5 up to Day 42) | 
| Change From Baseline for β-D-glucan Assay Results at Endpoints in Relation to Clinical Response Status of Success or Status of Failure at End of All Treatment | Change from baseline for β-D-glucan (range 0 to 6000 pg/mL) summarized at endpoints by subject's at end of all treatment clinical response status of Success at EOT or Failure at EOT and as combined status of All at EOT. Success=cure (resolution of signs, symptoms of Candida infection) or improvement (significant but incomplete resolution of signs, symptoms); failure=no significant improvement or death due to Candida infection; subject must have received at least 3 doses of anidulafungin. Percent change calculated as ([mean value of β-D-glucan at observation-baseline value]/baseline value*100). | Baseline, Day 3, Day 5, Day 7, EOT (Day 5 up to Day 42) | 
| Absolute Values for β-D-glucan Assay Results at Endpoints in Relation to Microbiological Response Status of Success or Status of Failure at End of All Treatment | Absolute values for β-D-glucan (range 0 to 6000 pg/mL) summarized at timeframe endpoints by subject's at end of all treatment microbiological response status of Success at EOT or Failure at EOT and as combined status of All at EOT. Success: eradication (follow up negative culture for Candida spp) or presumed eradication (follow up culture was not available and clinical outcome defined as success); failure: persistence (follow up culture was positive for at least 1 baseline Candida spp) or presumed persistence (follow up culture was not available and clinical outcome was defined as failure). | Baseline, Day 3, Day 5, Day 7, EOT (Day 5 up to Day 42) | 
| Change From Baseline for β-D-glucan Assay Results at Endpoints in Relation to Microbiological Response of Status of Success or Status of Failure at EOT | Change from baseline in β-D-glucan (range 0 to 6000 pg/mL) summarized at endpoints and by subject's EOT microbiological response status of Success at EOT or Failure at EOT and as combined status of All at EOT. Success=eradication (negative culture Candida spp or presumed eradication (culture not available, clinical outcome defined as success); failure=persistence (culture positive for at least 1 baseline Candida spp) or presumed persistence (culture not available, clinical outcome defined as failure). Percent change=([mean value of β-D-glucan at observation-baseline value]/baseline value*100). | Baseline, Day 3, Day 5, Day 7, EOT (Day 5 up to Day 42) | 
| Number of Subjects With Global Response of Success at EOT in Relation to Subject Subgroups | Number of subjects with clinician assessed global response of success at EOT (clinical=cure, improvement, microbiological=eradication, presumed eradication) in relation to subject subgroups (subject may be represented in >1 subgroup). Subgroups: Neutropenic status (absolute neutrophil count [ANC in cubic millimeters [cmm]); baseline pathogen; previous surgery (any surgery, abdominal surgery); organ transplantation (kidney, liver, heart); elderly; renal insufficiency (calculated creatinine clearance [CCC] in milliliters per minute [mL/min]); central venous catheter; receiving chemotherapy. | EOT (Day 5 up to Day 42) |