Candidemia
Conditions
Keywords
Phase 3b, Efficacy and Safety evaluation of Anidulafungin, ICC
Brief summary
In the treatment of patients with candidemia and/or other forms of invasive candidiasis , Anidulafungin is at least as effective and safe as Fluconazole.
Detailed description
To support anidulafungin NDA in China Due to the challenges in subject recruitment resulting in protracted study course, Pfizer Inc. has decided to terminate trial A8851023 prematurely based on the recommendation by the senior management team on November 8, 2011. The decision to terminate the trial was not based on any safety concerns. All investigators were verbally informed by the study team since November 8, 2011 to stop the subject recruitment as soon as possible. All 17 enrolled subjects have been followed up on safety issues and no safety concerns were present by the data of these subjects.
Interventions
DRUGAnidulafungin/Fluconazole
Anidulafungin:IV,100 mg daily preceded by an initial 200 mg dose on Day 1, 14 - 42 days Fluconazole: IV/Oral, 400mg,QD,14 - 42 days
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Presence of candidemia or invasive candidiasis. * Presence of one or more of signs and symptoms of acute fungal infection.
Exclusion criteria
* Subjects who received greater than 48 hours of systemic antifungal treatment for the Candida infection for which they will be enrolled. * Subjects with hypersensitivity to echinocandins or azole therapy or drug excipients.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Global Response at End of Intravenous Treatment (EOIT) | End of Intravenous Treatment (Up to Day 42) | Global response included clinical and microbiological success or failure. Success - clinical success (defined as the resolution or significant improvement in signs and symptoms of invasive candidiasis) and microbiological success (defined as the eradication of Candida species present at baseline, as determined on follow-up culture, or the presumed eradication, if culture data were not available \[N/A\] for a participant with a successful clinical response). Failure - Any case that did not meet the criteria for success. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Clinical Response at EOIT | End of Intravenous Treatment (Up to Day 42) | Clinical response included success and failure. Success included Cure (resolution of signs and symptoms of the Candida infection) and Improvement (significant, but incomplete resolution of signs and symptoms of Candida infection). Failure defined as No significant improvement in signs and symptoms or death due to Candida infection or circumstances prevented an evaluation from being made. |
| Percentage of Participants With Clinical Response at EOT | End of Treatment (Up to Day 42) | Clinical response included success and failure. Success included Cure (resolution of signs and symptoms of the Candida infection) and Improvement (significant, but incomplete resolution of signs and symptoms of Candida infection). Failure defined as No significant improvement in signs and symptoms or death due to Candida infection or circumstances prevented an evaluation from being made. |
| Percentage of Participants With Clinical Response at Follow-Up | Post treatment follow-up visit (Up to Day 52) | Clinical response included success and failure. Success included Cure (resolution of signs and symptoms of the Candida infection) and Improvement (significant, but incomplete resolution of signs and symptoms of Candida infection). Failure defined as No significant improvement in signs and symptoms or death due to Candida infection or circumstances prevented an evaluation from being made. |
| Percentage of Participants With Global Response at End of Treatment (EOT) | End of Treatment (Up to Day 42) | Global response included clinical and microbiological success or failure. Success - clinical success (defined as the resolution or significant improvement in signs and symptoms of invasive candidiasis) and microbiological success (defined as the eradication of Candida species present at baseline, as determined on follow-up culture, or the presumed eradication, if culture data were N/A for a participant with a successful clinical response). Failure - Any case that did not meet the criteria for success. |
| Percentage of Participants With Microbiological Response at EOT | End of Treatment (Up to Day 42) | Microbiological Success implies Eradication: culture negative for all Candida species present at baseline (documented), or culture data N/A (presumed). Microbiological Failure implies (1) Persistence: baseline Candida species present in repeat cultures (documented), or culture data N/A (presumed); (2) Recurrence: baseline Candida species isolated following eradication (documented), or culture data N/A (presumed); or (3) Indeterminate: culture data N/A (loss to follow-up or death that was not due to candidiasis or candidemia). |
| Percentage of Participants With Microbiological Response at Follow-Up | Post treatment follow-up visit (Up to Day 52) | Microbiological Success implies Eradication: culture negative for all Candida species present at baseline (documented), or culture data N/A (presumed). Microbiological Failure implies (1) Persistence: baseline Candida species present in repeat cultures (documented), or culture data N/A (presumed); (2) Recurrence: baseline Candida species isolated following eradication (documented), or culture data N/A (presumed); or (3) Indeterminate: culture data N/A (loss to follow-up or death that was not due to candidiasis or candidemia). |
| Number of Participants Who Died | Baseline to Day 52 | — |
| Percentage of Participants With Microbiological Response at EOIT | End of Intravenous Treatment (Up to Day 42) | Microbiological Success implies Eradication: culture negative for all Candida species present at baseline (documented), or culture data N/A (presumed). Microbiological Failure implies (1) Persistence: baseline Candida species present in repeat cultures (documented), or culture data N/A (presumed); (2) Recurrence: baseline Candida species isolated following eradication (documented), or culture data N/A (presumed); or (3) Indeterminate: culture data N/A (loss to follow-up or death that was not due to candidiasis or candidemia). |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Anidulafungin Intravenous (IV) Anidulafungin loading dose of 200 mg on Day 1 and then 100 mg daily from Day 2. Participants who completed a minimum of 7 days of IV treatment may have continued with IV treatment or may have been switched to oral fluconazole 400 mg daily up to a maximum of Day 42. | 9 |
| Fluconazole IV fluconazole 400 mg daily dose from Day 1 (dose reduction according to the participant's tolerability). Participants who completed a minimum of 7 days of IV treatment may have continued with IV treatment or may have been switched to oral fluconazole 400 mg daily up to a maximum of Day 42. | 8 |
| Total | 17 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Insufficient clinical response | 2 | 2 |
| Overall Study | Insufficient mycological response | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Anidulafungin | Fluconazole | Total |
|---|---|---|---|
| Age, Customized Between 18 and 44 years | 1 participants | 4 participants | 5 participants |
| Age, Customized Between 45 and 64 years | 4 participants | 2 participants | 6 participants |
| Age, Customized More than 65 years | 4 participants | 2 participants | 6 participants |
| Presence of Signs and Symptoms of Candidemia Feeling hot | 4 participants | 4 participants | 8 participants |
| Presence of Signs and Symptoms of Candidemia Fever | 7 participants | 7 participants | 14 participants |
| Presence of Signs and Symptoms of Candidemia Hypothermia | 0 participants | 0 participants | 0 participants |
| Presence of Signs and Symptoms of Candidemia Localized erythema | 1 participants | 0 participants | 1 participants |
| Presence of Signs and Symptoms of Candidemia Mechanical ventilation | 1 participants | 1 participants | 2 participants |
| Presence of Signs and Symptoms of Candidemia Other | 2 participants | 1 participants | 3 participants |
| Presence of Signs and Symptoms of Candidemia Partial pressure of carbon dioxide (PCO2) decrease | 0 participants | 1 participants | 1 participants |
| Presence of Signs and Symptoms of Candidemia Purulence | 1 participants | 2 participants | 3 participants |
| Presence of Signs and Symptoms of Candidemia Respiratory rate increased | 2 participants | 1 participants | 3 participants |
| Presence of Signs and Symptoms of Candidemia Swelling | 1 participants | 2 participants | 3 participants |
| Presence of Signs and Symptoms of Candidemia Tachycardia | 3 participants | 2 participants | 5 participants |
| Presence of Signs and Symptoms of Candidemia White blood cell count decreased | 2 participants | 0 participants | 2 participants |
| Presence of Signs and Symptoms of Candidemia White blood cell count increased | 3 participants | 1 participants | 4 participants |
| Presence of Signs and Symptoms of Candidemia White blood cell morphology abnormal | 0 participants | 1 participants | 1 participants |
| Sex: Female, Male Female | 1 Participants | 3 Participants | 4 Participants |
| Sex: Female, Male Male | 8 Participants | 5 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / 9 | 6 / 8 |
| serious Total, serious adverse events | 2 / 9 | 0 / 8 |
Outcome results
Primary
Percentage of Participants With Global Response at End of Intravenous Treatment (EOIT)
Global response included clinical and microbiological success or failure. Success - clinical success (defined as the resolution or significant improvement in signs and symptoms of invasive candidiasis) and microbiological success (defined as the eradication of Candida species present at baseline, as determined on follow-up culture, or the presumed eradication, if culture data were not available \[N/A\] for a participant with a successful clinical response). Failure - Any case that did not meet the criteria for success.
Time frame: End of Intravenous Treatment (Up to Day 42)
Population: Modified Intent-to-Treat (MITT) population: participants had confirmed diagnosis of candidemia or other forms of invasive candidiasis, received at least 1 dose of study medication treatment, had at least 1 post-baseline efficacy evaluation. N=number of participants with evaluable data; participants with missing or indeterminate data set to Failure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Anidulafungin | Percentage of Participants With Global Response at End of Intravenous Treatment (EOIT) | Success | 62.50 percentage of participants |
| Anidulafungin | Percentage of Participants With Global Response at End of Intravenous Treatment (EOIT) | Failure | 37.50 percentage of participants |
| Fluconazole | Percentage of Participants With Global Response at End of Intravenous Treatment (EOIT) | Success | 71.43 percentage of participants |
| Fluconazole | Percentage of Participants With Global Response at End of Intravenous Treatment (EOIT) | Failure | 28.57 percentage of participants |
Secondary
Number of Participants Who Died
Time frame: Baseline to Day 52
Population: Safety population: All participants who have received at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Anidulafungin | Number of Participants Who Died | 1 participants |
| Fluconazole | Number of Participants Who Died | 0 participants |
Secondary
Percentage of Participants With Clinical Response at EOIT
Clinical response included success and failure. Success included Cure (resolution of signs and symptoms of the Candida infection) and Improvement (significant, but incomplete resolution of signs and symptoms of Candida infection). Failure defined as No significant improvement in signs and symptoms or death due to Candida infection or circumstances prevented an evaluation from being made.
Time frame: End of Intravenous Treatment (Up to Day 42)
Population: MITT population. N=number of participants with evaluable data; participants with missing data set to Failure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Anidulafungin | Percentage of Participants With Clinical Response at EOIT | Success | 75.00 percentage of participants |
| Anidulafungin | Percentage of Participants With Clinical Response at EOIT | Failure | 25.00 percentage of participants |
| Fluconazole | Percentage of Participants With Clinical Response at EOIT | Success | 71.43 percentage of participants |
| Fluconazole | Percentage of Participants With Clinical Response at EOIT | Failure | 28.57 percentage of participants |
Secondary
Percentage of Participants With Clinical Response at EOT
Clinical response included success and failure. Success included Cure (resolution of signs and symptoms of the Candida infection) and Improvement (significant, but incomplete resolution of signs and symptoms of Candida infection). Failure defined as No significant improvement in signs and symptoms or death due to Candida infection or circumstances prevented an evaluation from being made.
Time frame: End of Treatment (Up to Day 42)
Population: MITT population. N=number of participants with evaluable data; participants with missing data set to Failure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Anidulafungin | Percentage of Participants With Clinical Response at EOT | Success | 75.00 percentage of participants |
| Anidulafungin | Percentage of Participants With Clinical Response at EOT | Failure | 25.00 percentage of participants |
| Fluconazole | Percentage of Participants With Clinical Response at EOT | Success | 57.14 percentage of participants |
| Fluconazole | Percentage of Participants With Clinical Response at EOT | Failure | 42.86 percentage of participants |
Secondary
Percentage of Participants With Clinical Response at Follow-Up
Clinical response included success and failure. Success included Cure (resolution of signs and symptoms of the Candida infection) and Improvement (significant, but incomplete resolution of signs and symptoms of Candida infection). Failure defined as No significant improvement in signs and symptoms or death due to Candida infection or circumstances prevented an evaluation from being made.
Time frame: Post treatment follow-up visit (Up to Day 52)
Population: MITT population. N=number of participants with evaluable data; participants with missing data set to Failure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Anidulafungin | Percentage of Participants With Clinical Response at Follow-Up | Failure | 25.00 percentage of participants |
| Anidulafungin | Percentage of Participants With Clinical Response at Follow-Up | Success | 75.00 percentage of participants |
| Fluconazole | Percentage of Participants With Clinical Response at Follow-Up | Success | 57.14 percentage of participants |
| Fluconazole | Percentage of Participants With Clinical Response at Follow-Up | Failure | 42.86 percentage of participants |
Secondary
Percentage of Participants With Global Response at End of Treatment (EOT)
Global response included clinical and microbiological success or failure. Success - clinical success (defined as the resolution or significant improvement in signs and symptoms of invasive candidiasis) and microbiological success (defined as the eradication of Candida species present at baseline, as determined on follow-up culture, or the presumed eradication, if culture data were N/A for a participant with a successful clinical response). Failure - Any case that did not meet the criteria for success.
Time frame: End of Treatment (Up to Day 42)
Population: MITT population. N=number of participants with evaluable data; participants with missing or indeterminate data set to Failure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Anidulafungin | Percentage of Participants With Global Response at End of Treatment (EOT) | Success | 62.50 percentage of participants |
| Anidulafungin | Percentage of Participants With Global Response at End of Treatment (EOT) | Failure | 37.50 percentage of participants |
| Fluconazole | Percentage of Participants With Global Response at End of Treatment (EOT) | Success | 42.86 percentage of participants |
| Fluconazole | Percentage of Participants With Global Response at End of Treatment (EOT) | Failure | 57.14 percentage of participants |
Secondary
Percentage of Participants With Microbiological Response at EOIT
Microbiological Success implies Eradication: culture negative for all Candida species present at baseline (documented), or culture data N/A (presumed). Microbiological Failure implies (1) Persistence: baseline Candida species present in repeat cultures (documented), or culture data N/A (presumed); (2) Recurrence: baseline Candida species isolated following eradication (documented), or culture data N/A (presumed); or (3) Indeterminate: culture data N/A (loss to follow-up or death that was not due to candidiasis or candidemia).
Time frame: End of Intravenous Treatment (Up to Day 42)
Population: MITT population. N=number of participants with evaluable data; participants with missing or indeterminate data are set Failure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Anidulafungin | Percentage of Participants With Microbiological Response at EOIT | Success | 75.00 percentage of participants |
| Anidulafungin | Percentage of Participants With Microbiological Response at EOIT | Failure | 25.00 percentage of participants |
| Fluconazole | Percentage of Participants With Microbiological Response at EOIT | Success | 85.71 percentage of participants |
| Fluconazole | Percentage of Participants With Microbiological Response at EOIT | Failure | 14.29 percentage of participants |
Secondary
Percentage of Participants With Microbiological Response at EOT
Microbiological Success implies Eradication: culture negative for all Candida species present at baseline (documented), or culture data N/A (presumed). Microbiological Failure implies (1) Persistence: baseline Candida species present in repeat cultures (documented), or culture data N/A (presumed); (2) Recurrence: baseline Candida species isolated following eradication (documented), or culture data N/A (presumed); or (3) Indeterminate: culture data N/A (loss to follow-up or death that was not due to candidiasis or candidemia).
Time frame: End of Treatment (Up to Day 42)
Population: MITT population. N=number of participants with evaluable data; participants with missing or indeterminate data are set to Failure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Anidulafungin | Percentage of Participants With Microbiological Response at EOT | Success | 75.00 percentage of participants |
| Anidulafungin | Percentage of Participants With Microbiological Response at EOT | Failure | 25.00 percentage of participants |
| Fluconazole | Percentage of Participants With Microbiological Response at EOT | Success | 57.14 percentage of participants |
| Fluconazole | Percentage of Participants With Microbiological Response at EOT | Failure | 42.86 percentage of participants |
Secondary
Percentage of Participants With Microbiological Response at Follow-Up
Microbiological Success implies Eradication: culture negative for all Candida species present at baseline (documented), or culture data N/A (presumed). Microbiological Failure implies (1) Persistence: baseline Candida species present in repeat cultures (documented), or culture data N/A (presumed); (2) Recurrence: baseline Candida species isolated following eradication (documented), or culture data N/A (presumed); or (3) Indeterminate: culture data N/A (loss to follow-up or death that was not due to candidiasis or candidemia).
Time frame: Post treatment follow-up visit (Up to Day 52)
Population: MITT population. N=number of participants with evaluable data; participants with missing or indeterminate data are set to Failure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Anidulafungin | Percentage of Participants With Microbiological Response at Follow-Up | Success | 62.50 percentage of participants |
| Anidulafungin | Percentage of Participants With Microbiological Response at Follow-Up | Failure | 37.50 percentage of participants |
| Fluconazole | Percentage of Participants With Microbiological Response at Follow-Up | Success | 57.14 percentage of participants |
| Fluconazole | Percentage of Participants With Microbiological Response at Follow-Up | Failure | 42.86 percentage of participants |