Candidiasis
Conditions
Keywords
candidemia, invasive candidiasis, fungal bloodstream infection
Brief summary
The purpose of this study is to further evaluate the safety and effectiveness of intravenous anidulafungin (Eraxis™) in patients with a diagnosis of candidemia or invasive candidiasis, which is a fungus infection of the blood or tissue. Currently the drug is approved for treatment using a daily dose of IV medication until 14 days after the fungus disappears from the blood. This study will evaluate the effectiveness of intravenous anidulafungin when it is administered for 5-28 days followed by oral antifungal medication. Study patients will be assessed for response to treatment throughout the study drug treatment period.
Interventions
DRUGEraxis (anidulafungin)
Subjects will receive IV anidulafungin (200 mg loading dose followed by 100 mg maintenance doses QD) for 5-28 days. This will be followed by oral therapy with fluconazole at 400 mg once daily or voriconazole at 200 mg twice daily until 14 days after the last positive culture. Fluconazole will be used if the baseline cultures are positive for C. albicans or C. parapsilosis while voriconazole will be used if cultures are positive for C. glabrata or other non-albicans species.
DRUGDiflucan (fluconazole)
Subjects will receive IV anidulafungin (200 mg loading dose followed by 100 mg maintenance doses QD) for 5-28 days. This will be followed by oral therapy with fluconazole at 400 mg once daily or voriconazole at 200 mg twice daily until 14 days after the last positive culture. Fluconazole will be used if the baseline cultures are positive for C. albicans or C. parapsilosis.
DRUGVfend (voriconazole)
Subjects will receive IV anidulafungin (200 mg loading dose followed by 100 mg maintenance doses QD) for 5-28 days. This will be followed by oral therapy with fluconazole at 400 mg once daily or voriconazole at 200 mg twice daily until 14 days after the last positive culture. Fluconazole will be used if the baseline cultures are positive for C. albicans or C. parapsilosis while voriconazole will be used if cultures are positive for C. glabrata or other non-albicans species.
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female subjects \> or equal to 18 years of age. * Presence of candidemia (positive blood culture) or invasive candidiasis (histopathologic or cytopathologic examination of a needle aspiration or biopsy specimen from a normally sterile site excluding mucous membranes showing yeast cells) obtained within the prior 96 hours of the screening visit. * Subjects who received no more than one prior dose of an echinocandin or polyene.
Exclusion criteria
* Subjects with hypersensitivity to anidulafungin, other echinocandins or azoles. * Presence of confirmed or suspected Candida osteomyelitis, endocarditis or meningitis. * Subjects with infected prosthetic devices which cannot be removed within 24 hours
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Global Response of Success or Failure (Based on Clinical and Microbiological Response) at End of Treatment (EOT) | End of Treatment (Day 5 up to Day 42) | Success: Clinical response=Cure (no signs, symptoms \[s/s\] of Candida) or Improvement (significant, incomplete resolution of s/s) and Microbiological response=Eradication (follow up \[f/u\] culture negative) or Presumed Eradication (f/u culture not available \[n/a\] and response of clinical success). Failure: Clinical response=Failure (≥3 doses Anidulafungin with no significant improvement in s/s or death due to Candida) and Microbiological response=Persistence (positive culture for ≥1 baseline Candida species \[spp\]) or Presumed Persistence (f/u culture n/a and clinical outcome= failure). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Microbiological Response at EOT | End of Treatment (Day 5 up to Day 42) | Microbiological Success=Eradication: negative culture for baseline Candida spp or Presumed Eradication: f/u culture n/a and clinical outcome defined as success (cure or improvement); Microbiological Failure=Persistence: positive culture for at least 1 baseline Candida spp or Presumed Persistence: f/u culture n/a and clinical outcome defined as failure (≥3 doses Anidulafungin with no significant improvement in s/s or death due to Candida). |
| Number of Participants With Global Response of Success or Failure (Based on Clinical and Microbiological Response) at End of Intravenous Treatment (EOIV) | End of Intravenous treatment (Day 5 up to Day 28) | Success: Clinical response=Cure (s/s of Candida) or Improvement (significant, incomplete resolution of s/s) and Microbiological response=Eradication (f/u culture negative) or Presumed Eradication (f/u culture n/a and response of clinical success). Failure: Clinical response=Failure (≥3 doses Anidulafungin with no significant improvement in s/s or death due to Candida) and Microbiological response=Persistence (positive culture for ≥1 baseline Candida spp) or Presumed Persistence (f/u culture n/a and clinical outcome= failure). |
| Number of Participants With Clinical Response at EOIV | End of Intravenous treatment (Day 5 up to Day 28) | Clinical Success=Cure: resolution of Candida s/s or Improvement: significant but incomplete resolution of s/s; Clinical Failure: at least 3 doses Anidulafungin with no significant improvement in s/s or death due to Candida. |
| Number of Participants With Microbiological Response at EOIV | End of Intravenous treatment (Day 5 up to Day 28) | Microbiological Success=Eradication: negative culture for baseline Candida spp or Presumed Eradication: f/u culture n/a and clinical outcome defined as success (cure or improvement); Microbiological Failure=Persistence: positive culture for at least 1 baseline Candida spp or Presumed Persistence: f/u culture n/a and clinical outcome defined as failure (≥3 doses Anidulafungin with no significant improvement in s/s or death due to Candida). |
| Number of Participants With Sustained (Continued) Global Response of Success or Failure (Based on Clinical and Microbiological Response) at Week 2 Follow-up | Week 2 Follow-up | Success: Clinical response=Cure (s/s of Candida) or Improvement (significant, incomplete resolution of s/s) and Microbiological response=Eradication (f/u culture negative) or Presumed Eradication (f/u culture n/a and response of clinical success). Failure: Clinical response=Failure (≥3 doses Anidulafungin with no significant improvement in s/s or death due to Candida) and Microbiological response=Persistence (positive culture for ≥1 baseline Candida spp) or Presumed Persistence (f/u culture n/a and clinical outcome= failure). |
| Number of Participants With Sustained (Continued) Clinical Response at Week 2 Follow-up | Week 2 follow-up | Clinical Success=Cure: resolution of Candida s/s or Improvement: significant but incomplete resolution of s/s; Clinical Failure: at least 3 doses Anidulafungin with no significant improvement in s/s or death due to Candida. |
| Number of Participants With Sustained (Continued) Microbiological Response at Week 2 Follow-up | Week 2 Follow-up | Microbiological Success=Eradication: negative culture for baseline Candida spp or Presumed Eradication: f/u culture n/a and clinical outcome defined as success (cure or improvement); Microbiological Failure=Persistence: positive culture for at least 1 baseline Candida spp or Presumed Persistence: f/u culture n/a and clinical outcome defined as failure (≥3 doses Anidulafungin with no significant improvement in s/s or death due to Candida). |
| Number of Participants With Sustained (Continued) Global Response of Success or Failure (Based on Clinical and Microbiological Response) at Week 6 Follow-up (End of Study [EOS]) | Week 6 Follow-up (EOS) | Success: Clinical response=Cure (s/s of Candida) or Improvement (significant, incomplete resolution of s/s) and Microbiological response=Eradication (f/u culture negative) or Presumed Eradication (f/u culture n/a and response of clinical success). Failure: Clinical response=Failure (≥3 doses Anidulafungin with no significant improvement in s/s or death due to Candida) and Microbiological response=Persistence (positive culture for ≥1 baseline Candida spp) or Presumed Persistence (f/u culture n/a and clinical outcome= failure). |
| Number of Participants With Sustained (Continued) Clinical Response at Week 6 Follow-up (EOS) | Week 6 follow-up (EOS) | Clinical Success=Cure: resolution of Candida s/s or Improvement: significant but incomplete resolution of s/s; Clinical Failure: at least 3 doses Anidulafungin with no significant improvement in s/s or death due to Candida. |
| Number of Participants With Sustained (Continued) Microbiological Response at Week 6 Follow-up (EOS) | Week 6 Follow-up (EOS) | Microbiological Success=Eradication: negative culture for baseline Candida spp or Presumed Eradication: f/u culture n/a and clinical outcome defined as success (cure or improvement); Microbiological Failure=Persistence: positive culture for at least 1 baseline Candida spp or Presumed Persistence: f/u culture n/a and clinical outcome defined as failure (≥3 doses Anidulafungin with no significant improvement in s/s or death due to Candida). |
| Number of Participants With Global Response of Success or Failure (Based on Clinical and Microbiological Response) at EOT for Participants With Non-albicans Candida at Baseline | End of Treatment (Day 5 up to Day 42) | Success: Clinical response=Cure (s/s of Candida) or Improvement (significant, incomplete resolution of s/s) and Microbiological response=Eradication (f/u culture negative) or Presumed Eradication (f/u culture n/a and response of clinical success). Failure: Clinical response=Failure (≥3 doses Anidulafungin with no significant improvement in s/s or death due to Candida) and Microbiological response=Persistence (positive culture for ≥1 baseline Candida spp) or Presumed Persistence (f/u culture n/a and clinical outcome= failure). |
| Number of Participants With Clinical Response at EOT | End of Treatment (Day 5 up to Day 42) | Clinical Success=Cure: resolution of Candida s/s or Improvement: significant but incomplete resolution of s/s; Clinical Failure: at least 3 doses Anidulafungin with no significant improvement in s/s or death due to Candida. |
| Number of Participants With Global Response of Success or Failure (Based on Clinical and Microbiological Response) at Week 2 Follow-up for Participants With Non-albicans Candida at Baseline | Week 2 Follow-up | Success: Clinical response=Cure (s/s of Candida) or Improvement (significant, incomplete resolution of s/s) and Microbiological response=Eradication (f/u culture negative) or Presumed Eradication (f/u culture n/a and response of clinical success). Failure: Clinical response=Failure (≥3 doses Anidulafungin with no significant improvement in s/s or death due to Candida) and Microbiological response=Persistence (positive culture for ≥1 baseline Candida spp) or Presumed Persistence (f/u culture n/a and clinical outcome= failure). |
| Number of Participants With Global Response of Success or Failure (Based on Clinical and Microbiological Response) at Week 6 Follow-up (EOS) for Participants With Non-albicans Candida at Baseline | Week 6 Follow-up (EOS) | Success: Clinical response=Cure (s/s of Candida) or Improvement (significant, incomplete resolution of s/s) and Microbiological response=Eradication (f/u culture negative) or Presumed Eradication (f/u culture n/a and response of clinical success). Failure: Clinical response=Failure (≥3 doses Anidulafungin with no significant improvement in s/s or death due to Candida) and Microbiological response=Persistence (positive culture for ≥1 baseline Candida spp) or Presumed Persistence (f/u culture n/a and clinical outcome= failure). |
| Time (75% Quartile Point Estimate) to Negative Blood and / or Tissue Culture for Candida Species | Baseline (Day 1) up to Week 6 Follow-up (EOS) | Participants with a negative culture on Day 1 were not included in the analysis. For participants with a positive culture on Day 1, the first day on which there was a negative culture was determined and then compared to the result of the next culture. If the next culture was also negative, or the next culture was positive but the interval between the 2 cultures was \> 3 days, the earlier of the 2 cultures was the day of first negative blood culture. If next culture was positive and taken within 3 days of the previous culture, the process was repeated with the next negative blood culture. |
| Medical Resource Utilization (MRU): Duration of Hospital Stay (Days) | Baseline up to 6 Week Follow-up (EOS) | Measured as time to dischargeable (medically dischargeable status) and as time to discharge (actual discharge). Analysis of length of hospital stay based on Kaplan-Meier survival techniques. |
| Medical Resource Utilization (MRU): Duration of Intensive Care Unit or Critical Care Unit Stay (Days) | Baseline up to 6 Week Follow-up (EOS) | Analysis of length of hospital stay based on Kaplan-Meier survival techniques. |
| Medical Resource Utilization (MRU): Duration of Intravenous Therapy (Days) | Baseline up to End of Intravenous treatment (Day 5 up to Day 28) | Analysis of length of hospital stay based on Kaplan-Meier survival techniques. |
| Medical Resource Utilization (MRU): Duration of Overall Therapy (Days) | Baseline up to End of Treatment (Day 5 up to Day 42) | Overall therapy includes Intravenous and Oral therapy. Participants were to receive at least 5 days and a maximum of 28 days of IV anidulafungin. After that, participants could continue treatment with oral fluconazole or voriconazole for at least 14 days from the day of last positive culture. |
| Number of Participants Per Specified Cause of Death | Baseline up to Week 6 Follow-up (EOS) or 30 days after last dose of study drug (whichever was later) | Cause of death (includes all-cause and attributable to Candida infection) reported based on death due to Serious Adverse Events (SAEs). SAEs are any untoward medical occurrence at any dose that results in death, is life threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, results in congenital anomaly or birth defect. Participants may be counted with \> 1 cause of death if multiple causes were present. |
| Number of Participants With Non-serious and Serious Adverse Events | Baseline up to Week 6 Follow-up (EOS) or 30 days after last dose of study drug (whichever was later) | AEs are any untoward medical occurrence in a clinical investigation subject administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. SAEs are any untoward medical occurrence at any dose that results in death, is life threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, results in congenital anomaly or birth defect. |
| Number of Participants Who Died | Baseline up to Week 6 Follow-up (EOS) or 30 days after last dose of study drug (whichever was later) | — |
| Number of Participants With Global Response of Success or Failure (Based on Clinical and Microbiological Response) at EOIV for Participants With Non-albicans Candida at Baseline | End of Intravenous treatment (Day 5 up to Day 28) | Success: Clinical response=Cure (s/s of Candida) or Improvement (significant, incomplete resolution of s/s) and Microbiological response=Eradication (f/u culture negative) or Presumed Eradication (f/u culture n/a and response of clinical success). Failure: Clinical response=Failure (≥3 doses Anidulafungin with no significant improvement in s/s or death due to Candida) and Microbiological response=Persistence (positive culture for ≥1 baseline Candida spp) or Presumed Persistence (f/u culture n/a and clinical outcome= failure). |
Countries
South Korea, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Anidulafungin Anidulafungin 200 milligrams (mg) intravenous (IV) loading dose followed by 100 mg IV infusion once a day (QD) for a minimum of 5 days and up to a maximum of 28 days. Participants who complete a minimum of 5 days IV treatment may be switched to oral (PO) fluconazole or voriconazole therapy any day between Day 6 and 28 dependent on criteria that includes negative blood cultures. Participants will continue on antifungal treatment for a minimum of 14 days after last positive blood and / or tissue culture and resolution of signs and symptoms of fungal infection. | 282 |
| Total | 282 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 13 |
| Overall Study | Discontinued study due to death | 43 |
| Overall Study | Does not meet entrance criteria | 5 |
| Overall Study | Insufficient bacteriological response | 10 |
| Overall Study | Insufficient clinical response | 3 |
| Overall Study | Lost to Follow-up | 11 |
| Overall Study | Other | 14 |
| Overall Study | Pathogen not isolated baseline specimen | 4 |
| Overall Study | Protocol Violation | 8 |
| Overall Study | Withdrawal by Subject | 11 |
Baseline characteristics
| Characteristic | Anidulafungin |
|---|---|
| Age, Customized 18 to 44 years of age | 72 participants |
| Age, Customized 45 to 64 years of age | 116 participants |
| Age, Customized ≥ 65 years of age | 94 participants |
| Sex: Female, Male Female | 131 Participants |
| Sex: Female, Male Male | 151 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 132 / 282 |
| serious Total, serious adverse events | 134 / 282 |
Outcome results
Primary
Number of Participants With Global Response of Success or Failure (Based on Clinical and Microbiological Response) at End of Treatment (EOT)
Success: Clinical response=Cure (no signs, symptoms \[s/s\] of Candida) or Improvement (significant, incomplete resolution of s/s) and Microbiological response=Eradication (follow up \[f/u\] culture negative) or Presumed Eradication (f/u culture not available \[n/a\] and response of clinical success). Failure: Clinical response=Failure (≥3 doses Anidulafungin with no significant improvement in s/s or death due to Candida) and Microbiological response=Persistence (positive culture for ≥1 baseline Candida species \[spp\]) or Presumed Persistence (f/u culture n/a and clinical outcome= failure).
Time frame: End of Treatment (Day 5 up to Day 42)
Population: Modified Intent to Treat population (MITT): includes all participants who received at least 1 dose of study medication and with a positive baseline culture for a Candida spp. N=number of participants included in analysis (participants with missing outcome values were excluded from the analysis).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Anidulafungin | Number of Participants With Global Response of Success or Failure (Based on Clinical and Microbiological Response) at End of Treatment (EOT) | Success (Cure or Improvement) | 170 participants |
| Anidulafungin | Number of Participants With Global Response of Success or Failure (Based on Clinical and Microbiological Response) at End of Treatment (EOT) | Failure | 33 participants |
Comparison: Global response of Success (cure or improvement) at EOT95% CI: [78.7, 88.8]
Secondary
Medical Resource Utilization (MRU): Duration of Hospital Stay (Days)
Measured as time to dischargeable (medically dischargeable status) and as time to discharge (actual discharge). Analysis of length of hospital stay based on Kaplan-Meier survival techniques.
Time frame: Baseline up to 6 Week Follow-up (EOS)
Population: MITT; N=number of participants with analyzable data at observation. Time to dischargeable and time to discharge censored at Week 6 Follow-up (EOS).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Anidulafungin | Medical Resource Utilization (MRU): Duration of Hospital Stay (Days) | Time to dischargeable | 27.3 days | Standard Error 3.24 |
| Anidulafungin | Medical Resource Utilization (MRU): Duration of Hospital Stay (Days) | Time to discharge | 27.1 days | Standard Error 3.02 |
Secondary
Medical Resource Utilization (MRU): Duration of Intensive Care Unit or Critical Care Unit Stay (Days)
Analysis of length of hospital stay based on Kaplan-Meier survival techniques.
Time frame: Baseline up to 6 Week Follow-up (EOS)
Population: MITT; N=number of participants with analyzable data at observation. Length of hospital stay censored at Week 6 Follow-up (EOS).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Anidulafungin | Medical Resource Utilization (MRU): Duration of Intensive Care Unit or Critical Care Unit Stay (Days) | 18.4 days | Standard Error 2.11 |
Secondary
Medical Resource Utilization (MRU): Duration of Intravenous Therapy (Days)
Analysis of length of hospital stay based on Kaplan-Meier survival techniques.
Time frame: Baseline up to End of Intravenous treatment (Day 5 up to Day 28)
Population: MITT; N=number of participants with analyzable data at observation. Length of hospital stay censored at Week 6 Follow-up (EOS).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Anidulafungin | Medical Resource Utilization (MRU): Duration of Intravenous Therapy (Days) | 8.9 days | Standard Error 0.37 |
Secondary
Medical Resource Utilization (MRU): Duration of Overall Therapy (Days)
Overall therapy includes Intravenous and Oral therapy. Participants were to receive at least 5 days and a maximum of 28 days of IV anidulafungin. After that, participants could continue treatment with oral fluconazole or voriconazole for at least 14 days from the day of last positive culture.
Time frame: Baseline up to End of Treatment (Day 5 up to Day 42)
Population: Intent to Treat (ITT) population includes all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Anidulafungin | Medical Resource Utilization (MRU): Duration of Overall Therapy (Days) | 14.1 days | Standard Deviation 8.21 |
Secondary
Number of Participants Per Specified Cause of Death
Cause of death (includes all-cause and attributable to Candida infection) reported based on death due to Serious Adverse Events (SAEs). SAEs are any untoward medical occurrence at any dose that results in death, is life threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, results in congenital anomaly or birth defect. Participants may be counted with \> 1 cause of death if multiple causes were present.
Time frame: Baseline up to Week 6 Follow-up (EOS) or 30 days after last dose of study drug (whichever was later)
Population: Safety analysis set is the same as the Intent-to-Treat population (ITT) and includes all participants who had taken at least 1 dose of study medication. N=number of participants who died with cause of death reported as Serious Adverse Events.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Anidulafungin | Number of Participants Per Specified Cause of Death | Fungaemia | 1 participants |
| Anidulafungin | Number of Participants Per Specified Cause of Death | Acute myocardial infarction | 1 participants |
| Anidulafungin | Number of Participants Per Specified Cause of Death | Acute respiratory failure | 1 participants |
| Anidulafungin | Number of Participants Per Specified Cause of Death | Anastomotic complication | 1 participants |
| Anidulafungin | Number of Participants Per Specified Cause of Death | Ascites | 2 participants |
| Anidulafungin | Number of Participants Per Specified Cause of Death | Atrial flutter | 1 participants |
| Anidulafungin | Number of Participants Per Specified Cause of Death | Bile duct cancer | 1 participants |
| Anidulafungin | Number of Participants Per Specified Cause of Death | Brain oedema | 1 participants |
| Anidulafungin | Number of Participants Per Specified Cause of Death | Cardiac arrest | 5 participants |
| Anidulafungin | Number of Participants Per Specified Cause of Death | Cardiac failure congestive | 1 participants |
| Anidulafungin | Number of Participants Per Specified Cause of Death | Cardio-respiratory arrest | 1 participants |
| Anidulafungin | Number of Participants Per Specified Cause of Death | Chronic hepatic failure | 2 participants |
| Anidulafungin | Number of Participants Per Specified Cause of Death | Coagulopathy | 1 participants |
| Anidulafungin | Number of Participants Per Specified Cause of Death | Colon cancer | 1 participants |
| Anidulafungin | Number of Participants Per Specified Cause of Death | Convulsion | 1 participants |
| Anidulafungin | Number of Participants Per Specified Cause of Death | Deep vein thrombosis | 1 participants |
| Anidulafungin | Number of Participants Per Specified Cause of Death | Diabetes mellitus | 1 participants |
| Anidulafungin | Number of Participants Per Specified Cause of Death | Disease progression | 8 participants |
| Anidulafungin | Number of Participants Per Specified Cause of Death | Dyspnoea | 1 participants |
| Anidulafungin | Number of Participants Per Specified Cause of Death | Electromechanical dissociation | 1 participants |
| Anidulafungin | Number of Participants Per Specified Cause of Death | Endocarditis | 1 participants |
| Anidulafungin | Number of Participants Per Specified Cause of Death | Endotracheal intubation | 1 participants |
| Anidulafungin | Number of Participants Per Specified Cause of Death | Gastrointestinal haemorrhage | 1 participants |
| Anidulafungin | Number of Participants Per Specified Cause of Death | Gastrointestinal ischaemia | 1 participants |
| Anidulafungin | Number of Participants Per Specified Cause of Death | General physical health deterioration | 1 participants |
| Anidulafungin | Number of Participants Per Specified Cause of Death | Haemorrhage | 1 participants |
| Anidulafungin | Number of Participants Per Specified Cause of Death | Haemorrhage intracranial | 1 participants |
| Anidulafungin | Number of Participants Per Specified Cause of Death | Hepatic failure | 1 participants |
| Anidulafungin | Number of Participants Per Specified Cause of Death | Hypoglycaemia | 2 participants |
| Anidulafungin | Number of Participants Per Specified Cause of Death | Hyponatraemia | 1 participants |
| Anidulafungin | Number of Participants Per Specified Cause of Death | Hypotension | 2 participants |
| Anidulafungin | Number of Participants Per Specified Cause of Death | Infection | 1 participants |
| Anidulafungin | Number of Participants Per Specified Cause of Death | Ischaemic cardiomyopathy | 1 participants |
| Anidulafungin | Number of Participants Per Specified Cause of Death | Liver function test abnormal | 1 participants |
| Anidulafungin | Number of Participants Per Specified Cause of Death | Lymphoma | 3 participants |
| Anidulafungin | Number of Participants Per Specified Cause of Death | Mental status changes | 1 participants |
| Anidulafungin | Number of Participants Per Specified Cause of Death | Metastatic gastric cancer | 1 participants |
| Anidulafungin | Number of Participants Per Specified Cause of Death | Multi-organ disorder | 1 participants |
| Anidulafungin | Number of Participants Per Specified Cause of Death | Multi-organ failure | 4 participants |
| Anidulafungin | Number of Participants Per Specified Cause of Death | Multiple myeloma | 1 participants |
| Anidulafungin | Number of Participants Per Specified Cause of Death | Multiple sclerosis relapse | 1 participants |
| Anidulafungin | Number of Participants Per Specified Cause of Death | Myocardial infarction | 1 participants |
| Anidulafungin | Number of Participants Per Specified Cause of Death | Neoplasm malignant | 1 participants |
| Anidulafungin | Number of Participants Per Specified Cause of Death | Peritonitis | 1 participants |
| Anidulafungin | Number of Participants Per Specified Cause of Death | Peritonitis bacterial | 1 participants |
| Anidulafungin | Number of Participants Per Specified Cause of Death | Pneumonia | 3 participants |
| Anidulafungin | Number of Participants Per Specified Cause of Death | Pneumothorax | 1 participants |
| Anidulafungin | Number of Participants Per Specified Cause of Death | Pulmonary embolism | 1 participants |
| Anidulafungin | Number of Participants Per Specified Cause of Death | Pulmonary haemorrhage | 1 participants |
| Anidulafungin | Number of Participants Per Specified Cause of Death | Renal failure | 5 participants |
| Anidulafungin | Number of Participants Per Specified Cause of Death | Renal failure acute | 1 participants |
| Anidulafungin | Number of Participants Per Specified Cause of Death | Renal failure chronic | 1 participants |
| Anidulafungin | Number of Participants Per Specified Cause of Death | Respiratory arrest | 3 participants |
| Anidulafungin | Number of Participants Per Specified Cause of Death | Respiratory distress | 2 participants |
| Anidulafungin | Number of Participants Per Specified Cause of Death | Respiratory failure | 6 participants |
| Anidulafungin | Number of Participants Per Specified Cause of Death | Sepsis | 12 participants |
| Anidulafungin | Number of Participants Per Specified Cause of Death | Septic shock | 7 participants |
| Anidulafungin | Number of Participants Per Specified Cause of Death | Systemic candida | 1 participants |
| Anidulafungin | Number of Participants Per Specified Cause of Death | Thrombocytopenia | 1 participants |
| Anidulafungin | Number of Participants Per Specified Cause of Death | Wound dehiscence | 1 participants |
Secondary
Number of Participants Who Died
Time frame: Baseline up to Week 6 Follow-up (EOS) or 30 days after last dose of study drug (whichever was later)
Population: Safety analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Anidulafungin | Number of Participants Who Died | 65 participants |
Secondary
Number of Participants With Clinical Response at EOIV
Clinical Success=Cure: resolution of Candida s/s or Improvement: significant but incomplete resolution of s/s; Clinical Failure: at least 3 doses Anidulafungin with no significant improvement in s/s or death due to Candida.
Time frame: End of Intravenous treatment (Day 5 up to Day 28)
Population: MITT; N=number of participants included in analysis (participants with missing outcome values were excluded from the analysis).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Anidulafungin | Number of Participants With Clinical Response at EOIV | Cure | 159 participants |
| Anidulafungin | Number of Participants With Clinical Response at EOIV | Improvement | 57 participants |
| Anidulafungin | Number of Participants With Clinical Response at EOIV | Failure | 16 participants |
Comparison: Clinical response of Success (cure or improvement) at EOIV95% CI: [89.8, 96.4]
Secondary
Number of Participants With Clinical Response at EOT
Clinical Success=Cure: resolution of Candida s/s or Improvement: significant but incomplete resolution of s/s; Clinical Failure: at least 3 doses Anidulafungin with no significant improvement in s/s or death due to Candida.
Time frame: End of Treatment (Day 5 up to Day 42)
Population: MITT; N=number of participants included in analysis (participants with missing outcome values were excluded from the analysis).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Anidulafungin | Number of Participants With Clinical Response at EOT | Cure | 160 participants |
| Anidulafungin | Number of Participants With Clinical Response at EOT | Improvement | 14 participants |
| Anidulafungin | Number of Participants With Clinical Response at EOT | Failure | 13 participants |
Comparison: Clinical response of Success (cure or improvement) at EOT95% CI: [89.4, 96.7]
Secondary
Number of Participants With Global Response of Success or Failure (Based on Clinical and Microbiological Response) at End of Intravenous Treatment (EOIV)
Success: Clinical response=Cure (s/s of Candida) or Improvement (significant, incomplete resolution of s/s) and Microbiological response=Eradication (f/u culture negative) or Presumed Eradication (f/u culture n/a and response of clinical success). Failure: Clinical response=Failure (≥3 doses Anidulafungin with no significant improvement in s/s or death due to Candida) and Microbiological response=Persistence (positive culture for ≥1 baseline Candida spp) or Presumed Persistence (f/u culture n/a and clinical outcome= failure).
Time frame: End of Intravenous treatment (Day 5 up to Day 28)
Population: MITT; N=number of participants included in analysis (participants with missing outcome values were excluded from the analysis).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Anidulafungin | Number of Participants With Global Response of Success or Failure (Based on Clinical and Microbiological Response) at End of Intravenous Treatment (EOIV) | Success (Cure or Improvement) | 208 participants |
| Anidulafungin | Number of Participants With Global Response of Success or Failure (Based on Clinical and Microbiological Response) at End of Intravenous Treatment (EOIV) | Failure | 27 participants |
Comparison: Global response of Success (cure or improvement) at EOIV95% CI: [84.4, 92.6]
Secondary
Number of Participants With Global Response of Success or Failure (Based on Clinical and Microbiological Response) at EOIV for Participants With Non-albicans Candida at Baseline
Success: Clinical response=Cure (s/s of Candida) or Improvement (significant, incomplete resolution of s/s) and Microbiological response=Eradication (f/u culture negative) or Presumed Eradication (f/u culture n/a and response of clinical success). Failure: Clinical response=Failure (≥3 doses Anidulafungin with no significant improvement in s/s or death due to Candida) and Microbiological response=Persistence (positive culture for ≥1 baseline Candida spp) or Presumed Persistence (f/u culture n/a and clinical outcome= failure).
Time frame: End of Intravenous treatment (Day 5 up to Day 28)
Population: MITT; N=number of participants in the MITT population where the pathogen isolated at baseline was a Candida spp. other than Candida albicans (participants with missing outcome values were excluded from the analysis).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Anidulafungin | Number of Participants With Global Response of Success or Failure (Based on Clinical and Microbiological Response) at EOIV for Participants With Non-albicans Candida at Baseline | Success (Cure or Improvement) | 119 participants |
| Anidulafungin | Number of Participants With Global Response of Success or Failure (Based on Clinical and Microbiological Response) at EOIV for Participants With Non-albicans Candida at Baseline | Failure | 20 participants |
Comparison: Global response of Success (cure or improvement) at EOIV95% CI: [79.8, 91.4]
Secondary
Number of Participants With Global Response of Success or Failure (Based on Clinical and Microbiological Response) at EOT for Participants With Non-albicans Candida at Baseline
Success: Clinical response=Cure (s/s of Candida) or Improvement (significant, incomplete resolution of s/s) and Microbiological response=Eradication (f/u culture negative) or Presumed Eradication (f/u culture n/a and response of clinical success). Failure: Clinical response=Failure (≥3 doses Anidulafungin with no significant improvement in s/s or death due to Candida) and Microbiological response=Persistence (positive culture for ≥1 baseline Candida spp) or Presumed Persistence (f/u culture n/a and clinical outcome= failure).
Time frame: End of Treatment (Day 5 up to Day 42)
Population: MITT; N=number of participants in the MITT population where the pathogen isolated at baseline was a Candida spp. other than Candida albicans (participants with missing outcome values were excluded from the analysis).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Anidulafungin | Number of Participants With Global Response of Success or Failure (Based on Clinical and Microbiological Response) at EOT for Participants With Non-albicans Candida at Baseline | Success (Cure or Improvement) | 99 participants |
| Anidulafungin | Number of Participants With Global Response of Success or Failure (Based on Clinical and Microbiological Response) at EOT for Participants With Non-albicans Candida at Baseline | Failure | 21 participants |
Comparison: Global response of Success (cure or improvement) at EOT95% CI: [75.7, 89.3]
Secondary
Number of Participants With Global Response of Success or Failure (Based on Clinical and Microbiological Response) at Week 2 Follow-up for Participants With Non-albicans Candida at Baseline
Success: Clinical response=Cure (s/s of Candida) or Improvement (significant, incomplete resolution of s/s) and Microbiological response=Eradication (f/u culture negative) or Presumed Eradication (f/u culture n/a and response of clinical success). Failure: Clinical response=Failure (≥3 doses Anidulafungin with no significant improvement in s/s or death due to Candida) and Microbiological response=Persistence (positive culture for ≥1 baseline Candida spp) or Presumed Persistence (f/u culture n/a and clinical outcome= failure).
Time frame: Week 2 Follow-up
Population: MITT; N=number of participants in the MITT population where the pathogen isolated at baseline was a Candida spp. other than Candida albicans (participants with missing outcome values were excluded from the analysis).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Anidulafungin | Number of Participants With Global Response of Success or Failure (Based on Clinical and Microbiological Response) at Week 2 Follow-up for Participants With Non-albicans Candida at Baseline | Success (Cure or Improvement) | 89 participants |
| Anidulafungin | Number of Participants With Global Response of Success or Failure (Based on Clinical and Microbiological Response) at Week 2 Follow-up for Participants With Non-albicans Candida at Baseline | Failure | 27 participants |
Comparison: Global response of Success (cure or improvement) at Week 2 Follow-up95% CI: [69, 84.4]
Secondary
Number of Participants With Global Response of Success or Failure (Based on Clinical and Microbiological Response) at Week 6 Follow-up (EOS) for Participants With Non-albicans Candida at Baseline
Success: Clinical response=Cure (s/s of Candida) or Improvement (significant, incomplete resolution of s/s) and Microbiological response=Eradication (f/u culture negative) or Presumed Eradication (f/u culture n/a and response of clinical success). Failure: Clinical response=Failure (≥3 doses Anidulafungin with no significant improvement in s/s or death due to Candida) and Microbiological response=Persistence (positive culture for ≥1 baseline Candida spp) or Presumed Persistence (f/u culture n/a and clinical outcome= failure).
Time frame: Week 6 Follow-up (EOS)
Population: MITT; N=number of participants in the MITT population where the pathogen isolated at baseline was a Candida spp. other than Candida albicans (participants with missing outcome values were excluded from the analysis).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Anidulafungin | Number of Participants With Global Response of Success or Failure (Based on Clinical and Microbiological Response) at Week 6 Follow-up (EOS) for Participants With Non-albicans Candida at Baseline | Success (Cure or Improvement) | 75 participants |
| Anidulafungin | Number of Participants With Global Response of Success or Failure (Based on Clinical and Microbiological Response) at Week 6 Follow-up (EOS) for Participants With Non-albicans Candida at Baseline | Failure | 36 participants |
Comparison: Global response of Success (cure or improvement) at Week 6 Follow-up (EOS)95% CI: [58.9, 76.3]
Secondary
Number of Participants With Microbiological Response at EOIV
Microbiological Success=Eradication: negative culture for baseline Candida spp or Presumed Eradication: f/u culture n/a and clinical outcome defined as success (cure or improvement); Microbiological Failure=Persistence: positive culture for at least 1 baseline Candida spp or Presumed Persistence: f/u culture n/a and clinical outcome defined as failure (≥3 doses Anidulafungin with no significant improvement in s/s or death due to Candida).
Time frame: End of Intravenous treatment (Day 5 up to Day 28)
Population: MITT; N=number of participants included in analysis (participants with missing outcome values were excluded from the analysis).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Anidulafungin | Number of Participants With Microbiological Response at EOIV | Eradication | 163 participants |
| Anidulafungin | Number of Participants With Microbiological Response at EOIV | Presumed eradication | 61 participants |
| Anidulafungin | Number of Participants With Microbiological Response at EOIV | Persistence | 15 participants |
| Anidulafungin | Number of Participants With Microbiological Response at EOIV | Presumed persistence | 3 participants |
Comparison: Microbiological response of Success (eradication or presumed eradication) at EOIV95% CI: [89.3, 95.9]
Secondary
Number of Participants With Microbiological Response at EOT
Microbiological Success=Eradication: negative culture for baseline Candida spp or Presumed Eradication: f/u culture n/a and clinical outcome defined as success (cure or improvement); Microbiological Failure=Persistence: positive culture for at least 1 baseline Candida spp or Presumed Persistence: f/u culture n/a and clinical outcome defined as failure (≥3 doses Anidulafungin with no significant improvement in s/s or death due to Candida).
Time frame: End of Treatment (Day 5 up to Day 42)
Population: MITT; N=number of participants included in analysis (participants with missing outcome values were excluded from the analysis).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Anidulafungin | Number of Participants With Microbiological Response at EOT | Eradication | 124 participants |
| Anidulafungin | Number of Participants With Microbiological Response at EOT | Presumed eradication | 59 participants |
| Anidulafungin | Number of Participants With Microbiological Response at EOT | Persistence | 6 participants |
| Anidulafungin | Number of Participants With Microbiological Response at EOT | Presumed persistence | 3 participants |
Comparison: Microbiological response of Success (eradication or presumed eradication) at EOT95% CI: [92.3, 98.3]
Secondary
Number of Participants With Non-serious and Serious Adverse Events
AEs are any untoward medical occurrence in a clinical investigation subject administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. SAEs are any untoward medical occurrence at any dose that results in death, is life threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, results in congenital anomaly or birth defect.
Time frame: Baseline up to Week 6 Follow-up (EOS) or 30 days after last dose of study drug (whichever was later)
Population: Safety analysis set. An event may have been reported as both a serious and non-serious adverse event, however, what is presented are distinct events; participants may be counted as having experienced \> 1 event.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Anidulafungin | Number of Participants With Non-serious and Serious Adverse Events | Non-serious Adverse Events | 216 participants |
| Anidulafungin | Number of Participants With Non-serious and Serious Adverse Events | Serious Adverse Events | 134 participants |
Secondary
Number of Participants With Sustained (Continued) Clinical Response at Week 2 Follow-up
Clinical Success=Cure: resolution of Candida s/s or Improvement: significant but incomplete resolution of s/s; Clinical Failure: at least 3 doses Anidulafungin with no significant improvement in s/s or death due to Candida.
Time frame: Week 2 follow-up
Population: MITT; N=number of participants included in analysis (participants with missing outcome values were excluded from the analysis).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Anidulafungin | Number of Participants With Sustained (Continued) Clinical Response at Week 2 Follow-up | Cure | 155 participants |
| Anidulafungin | Number of Participants With Sustained (Continued) Clinical Response at Week 2 Follow-up | Improvement | 9 participants |
| Anidulafungin | Number of Participants With Sustained (Continued) Clinical Response at Week 2 Follow-up | Failure | 9 participants |
Comparison: Clinical response of Success (cure or improvement) at Week 2 Follow-up95% CI: [91.5, 98.1]
Secondary
Number of Participants With Sustained (Continued) Clinical Response at Week 6 Follow-up (EOS)
Clinical Success=Cure: resolution of Candida s/s or Improvement: significant but incomplete resolution of s/s; Clinical Failure: at least 3 doses Anidulafungin with no significant improvement in s/s or death due to Candida.
Time frame: Week 6 follow-up (EOS)
Population: MITT; N=number of participants included in analysis (participants with missing outcome values were excluded from the analysis).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Anidulafungin | Number of Participants With Sustained (Continued) Clinical Response at Week 6 Follow-up (EOS) | Cure | 138 participants |
| Anidulafungin | Number of Participants With Sustained (Continued) Clinical Response at Week 6 Follow-up (EOS) | Improvement | 8 participants |
| Anidulafungin | Number of Participants With Sustained (Continued) Clinical Response at Week 6 Follow-up (EOS) | Failure | 10 participants |
Comparison: Clinical response of Success (cure or improvement) at Week 6 Follow-up (EOS)95% CI: [89.7, 97.4]
Secondary
Number of Participants With Sustained (Continued) Global Response of Success or Failure (Based on Clinical and Microbiological Response) at Week 2 Follow-up
Success: Clinical response=Cure (s/s of Candida) or Improvement (significant, incomplete resolution of s/s) and Microbiological response=Eradication (f/u culture negative) or Presumed Eradication (f/u culture n/a and response of clinical success). Failure: Clinical response=Failure (≥3 doses Anidulafungin with no significant improvement in s/s or death due to Candida) and Microbiological response=Persistence (positive culture for ≥1 baseline Candida spp) or Presumed Persistence (f/u culture n/a and clinical outcome= failure).
Time frame: Week 2 Follow-up
Population: MITT; N=number of participants included in analysis (participants with missing outcome values were excluded from the analysis).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Anidulafungin | Number of Participants With Sustained (Continued) Global Response of Success or Failure (Based on Clinical and Microbiological Response) at Week 2 Follow-up | Success (Cure or Improvement) | 148 participants |
| Anidulafungin | Number of Participants With Sustained (Continued) Global Response of Success or Failure (Based on Clinical and Microbiological Response) at Week 2 Follow-up | Failure | 46 participants |
Comparison: Global response of Success (cure or improvement) at Week 2 Follow-up95% CI: [70.3, 82.3]
Secondary
Number of Participants With Sustained (Continued) Global Response of Success or Failure (Based on Clinical and Microbiological Response) at Week 6 Follow-up (End of Study [EOS])
Success: Clinical response=Cure (s/s of Candida) or Improvement (significant, incomplete resolution of s/s) and Microbiological response=Eradication (f/u culture negative) or Presumed Eradication (f/u culture n/a and response of clinical success). Failure: Clinical response=Failure (≥3 doses Anidulafungin with no significant improvement in s/s or death due to Candida) and Microbiological response=Persistence (positive culture for ≥1 baseline Candida spp) or Presumed Persistence (f/u culture n/a and clinical outcome= failure).
Time frame: Week 6 Follow-up (EOS)
Population: MITT; N=number of participants included in analysis (participants with missing outcome values were excluded from the analysis).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Anidulafungin | Number of Participants With Sustained (Continued) Global Response of Success or Failure (Based on Clinical and Microbiological Response) at Week 6 Follow-up (End of Study [EOS]) | Success (Cure or Improvement) | 131 participants |
| Anidulafungin | Number of Participants With Sustained (Continued) Global Response of Success or Failure (Based on Clinical and Microbiological Response) at Week 6 Follow-up (End of Study [EOS]) | Failure | 56 participants |
Comparison: Global response of Success (cure or improvement) at Week 6 Follow-up (EOS)95% CI: [63.5, 76.6]
Secondary
Number of Participants With Sustained (Continued) Microbiological Response at Week 2 Follow-up
Microbiological Success=Eradication: negative culture for baseline Candida spp or Presumed Eradication: f/u culture n/a and clinical outcome defined as success (cure or improvement); Microbiological Failure=Persistence: positive culture for at least 1 baseline Candida spp or Presumed Persistence: f/u culture n/a and clinical outcome defined as failure (≥3 doses Anidulafungin with no significant improvement in s/s or death due to Candida).
Time frame: Week 2 Follow-up
Population: MITT; N=number of participants included in analysis (participants with missing outcome values were excluded from the analysis).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Anidulafungin | Number of Participants With Sustained (Continued) Microbiological Response at Week 2 Follow-up | Eradication | 30 participants |
| Anidulafungin | Number of Participants With Sustained (Continued) Microbiological Response at Week 2 Follow-up | Presumed eradication | 135 participants |
| Anidulafungin | Number of Participants With Sustained (Continued) Microbiological Response at Week 2 Follow-up | Persistence | 3 participants |
| Anidulafungin | Number of Participants With Sustained (Continued) Microbiological Response at Week 2 Follow-up | Presumed persistence | 5 participants |
Comparison: Microbiological response of Success (eradication or presumed eradication) at Week 2 Follow-up95% CI: [92.2, 98.5]
Secondary
Number of Participants With Sustained (Continued) Microbiological Response at Week 6 Follow-up (EOS)
Microbiological Success=Eradication: negative culture for baseline Candida spp or Presumed Eradication: f/u culture n/a and clinical outcome defined as success (cure or improvement); Microbiological Failure=Persistence: positive culture for at least 1 baseline Candida spp or Presumed Persistence: f/u culture n/a and clinical outcome defined as failure (≥3 doses Anidulafungin with no significant improvement in s/s or death due to Candida).
Time frame: Week 6 Follow-up (EOS)
Population: MITT; N=number of participants included in analysis (participants with missing outcome values were excluded from the analysis).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Anidulafungin | Number of Participants With Sustained (Continued) Microbiological Response at Week 6 Follow-up (EOS) | Presumed eradication | 134 participants |
| Anidulafungin | Number of Participants With Sustained (Continued) Microbiological Response at Week 6 Follow-up (EOS) | Eradication | 12 participants |
| Anidulafungin | Number of Participants With Sustained (Continued) Microbiological Response at Week 6 Follow-up (EOS) | Persistence | 2 participants |
| Anidulafungin | Number of Participants With Sustained (Continued) Microbiological Response at Week 6 Follow-up (EOS) | Presumed persistence | 8 participants |
Comparison: Microbiological response of Success (eradication or presumed eradication) at Week 6 Follow-up (EOS)95% CI: [89.7, 97.4]
Secondary
Time (75% Quartile Point Estimate) to Negative Blood and / or Tissue Culture for Candida Species
Participants with a negative culture on Day 1 were not included in the analysis. For participants with a positive culture on Day 1, the first day on which there was a negative culture was determined and then compared to the result of the next culture. If the next culture was also negative, or the next culture was positive but the interval between the 2 cultures was \> 3 days, the earlier of the 2 cultures was the day of first negative blood culture. If next culture was positive and taken within 3 days of the previous culture, the process was repeated with the next negative blood culture.
Time frame: Baseline (Day 1) up to Week 6 Follow-up (EOS)
Population: MITT; Confidence interval (CI) for the median could not be calculated by the software because no event time met the criteria for inclusion into the CI.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Anidulafungin | Time (75% Quartile Point Estimate) to Negative Blood and / or Tissue Culture for Candida Species | 3.0000 days |