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The purpose of this study is to provide anidulafungin and voriconazole to healthy subjects to determine the drug concentration in the lung.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| anidulafungin and voriconazole | Drug | Subjects will be admitted to the clinical research unit on Day 0. Subjects will receive anidulafungin intravenously in a loading dose of 200 mg on Day 1, followed by maintenance doses of 100 mg Q24h on Day 2 and Day 3. Simultaneously, using a separate intravenous access, subjects will receive voriconazole in a loading dose of 6 mg/kg Q12h on Day 1, followed by a maintenance dose of 4 mg/kg Q12h on Day 2, and a 4 mg/kg morning dose on Day 3. |
| Measure | Description | Time Frame |
|---|---|---|
| Plasma Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) | Cmax = maximum observed plasma concentration; measured in micrograms per milliliter (ug/mL). Observed directly from the data. Collected on Day 3. | 100 minutes (end of infusion), 2, 4, 8, 12, 24 hours after start of infusion |
| Plasma PK: Time to Reach Maximum Plasma Concentration (Tmax) | Tmax = time (hours) to maximum plasma concentration (Cmax). Observed directly from data as time of first occurrence. Collected on Day 3. | 100 minutes (end of infusion), 2, 4, 8, 12, 24 hours after start of infusion |
| Plasma PK: Area Under the Curve From Time Zero to Time = Tau (AUCtau) | AUCtau = area under the plasma concentration-time profile from time zero (0) to time = t (AUCt), the dosing interval, where t is 24 hours for anidulafungin and 12 hours for voriconazole; measured as micrograms times hours per milliliter (ug*hr/mL). Collected on Day 3. | 100 minutes (end of infusion), 2, 4, 8, 12, 24 hours after start of infusion |
| Plasma PK: Plasma Elimination Half-life (t1/2) | t1/2 = terminal elimination half-life in hours; Loge(2)/Kel, where Kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Collected on Day 3. | 100 minutes (end of infusion), 2, 4, 8, 12, 24 hours after start of infusion |
| Plasma PK: Total Clearance (CL Total) | CL total = total clearance calculated as dose divided by AUCt; measured as milliliters per minute (mL/min). Collected on Day 3. | 100 minutes (end of infusion), 2, 4, 8, 12, 24 hours after start of infusion |
| Plasma PK: Volume of Distribution at Steady-state (Vss) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Pfizer CT.gov Call Center | Pfizer | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Pfizer Investigational Site | Hartford | Connecticut | 06102 | United States |
Not provided
| Label | URL |
|---|---|
| To obtain contact information for a study center near you, click here. | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | Anidulafungin and Voriconazole | Anidulafungin (Eraxis™) intravenously (IV) in a loading dose of 200 milligrams (mg) on Day 1, followed by maintenance doses of 100 mg every 24 hours on Day 2 and Day 3. Simultaneously, using a separate intravenous access, subjects received voriconazole (Vfend®) in a loading dose of 6 milligrams per kilogram (mg/kg) every 12 hours on Day 1, followed by a maintenance dose of 4 mg/kg every 12 hours on Day 2, and a 4 mg/kg morning dose on Day 3. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Anidulafungin and Voriconazole | Anidulafungin (Eraxis™) intravenously (IV) in a loading dose of 200 milligrams (mg) on Day 1, followed by maintenance doses of 100 mg every 24 hours on Day 2 and Day 3. Simultaneously, using a separate intravenous access, subjects received voriconazole (Vfend®) in a loading dose of 6 milligrams per kilogram (mg/kg) every 12 hours on Day 1, followed by a maintenance dose of 4 mg/kg every 12 hours on Day 2, and a 4 mg/kg morning dose on Day 3. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Plasma Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) | Cmax = maximum observed plasma concentration; measured in micrograms per milliliter (ug/mL). Observed directly from the data. Collected on Day 3. | PK parameter analysis population | Posted | Mean | Standard Deviation | ug/mL | 100 minutes (end of infusion), 2, 4, 8, 12, 24 hours after start of infusion |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Anidulafungin and Voriconazole | Anidulafungin (Eraxis™) intravenously (IV) in a loading dose of 200 milligrams (mg) on Day 1, followed by maintenance doses of 100 mg every 24 hours on Day 2 and Day 3. Simultaneously, using a separate intravenous access, subjects received voriconazole (Vfend®) in a loading dose of 6 milligrams per kilogram (mg/kg) every 12 hours on Day 1, followed by a maintenance dose of 4 mg/kg every 12 hours on Day 2, and a 4 mg/kg morning dose on Day 3. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Photophobia | Eye disorders | MedDRA (12.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Pfizer ClinicalTrials.gov Call Center | Pfizer, Inc. | 1-800-718-1021 | ClinicalTrials.govCallCenter@pfizer.com |
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| ID | Term |
|---|---|
| D001228 | Aspergillosis |
| D058387 | Candidemia |
| D009181 | Mycoses |
| ID | Term |
|---|---|
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
| D058365 | Candidiasis, Invasive |
| D002177 | Candidiasis |
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| ID | Term |
|---|---|
| D000077612 | Anidulafungin |
| D065819 | Voriconazole |
| ID | Term |
|---|---|
| D054714 | Echinocandins |
| D010456 | Peptides, Cyclic |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
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|
Vss = volume of distribution at steady-state; measured as liters (L). Calculated as (CL multiplied by mean residence time extrapolated to infinity [MRTinf]). MRTinf = [(AUMCt plus t (AUCinf minus AUCt)) divided by AUCt] minus (infusion time divided by 2); AUMCt = area under the first moment curve from time zero to time t; AUCinf = area under the plasma concentration-time curve extrapolated to infinity. |
| 100 minutes (end of infusion), 2, 4, 8, 12, 24 hours after start of infusion |
| Epithelial Lining Fluid (ELF) PK: Cmax | Cmax=maximum observed plasma concentration. ELF collected by bronchoscopy and bronchoalveolar lavage (BAL) Day 3; determined from BAL sample using urea dilution method: [Drug ELF]=[Drug BAL] multiplied by [Urea SERUM] divided by [Urea BAL]. Drug ELF=anidulafungin or voriconazole (drug) concentration in ELF corrected for dilution; Drug BAL=assayed drug concentration in BAL; Urea SERUM and Urea BAL simultaneously collected. Summary parameters derived using average data for all subjects; associated to a single subject for reporting purposes (mean with standard deviation not calculated). | 4, 8, 12, 24 hours after start of infusion |
| ELF PK: Tmax | Tmax = time (hours) to maximum plasma concentration (Cmax). Observed directly from data as time of first occurrence. ELF collected by bronchoscopy and BAL on Day 3. | 4, 8, 12, 24 hours after start of infusion |
| ELF PK: AUCtau | AUCtau = area under the plasma concentration-time profile from time zero (0) to time = t (AUCt), the dosing interval, where t is 24 hours for anidulafungin and 12 hours for voriconazole. ELF collected by bronchoscopy and BAL on Day 3. Summary parameters were derived using average data for all subjects and associated to a single subject for reporting purposes (mean with standard deviation was not calculated). | 4, 8, 12, 24 hours after start of infusion |
| ELF PK: t1/2 | t1/2 = terminal elimination half-life in hours; Loge(2)/Kel, where Kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. ELF collected by bronchoscopy and BAL on Day 3. | 4, 8, 12, 24 hours after start of infusion |
| Alveolar Macrophages (AM): Cmax | Cmax = maximum observed plasma concentration; observed directly from the data. AM collected by bronchoscopy and BAL on Day 3. Summary parameters were derived using average data for all subjects and associated to a single subject for reporting purposes (mean with standard deviation was not calculated). | 4, 8, 12, 24 hours after start of infusion |
| AM: Tmax | Tmax = time (hours) to maximum plasma concentration (Cmax). Observed directly from data as time of first occurrence. AM collected by bronchoscopy and BAL on Day 3. | 4, 8, 12, 24 hours after start of infusion |
| AM: AUCtau | AUCtau = area under the plasma concentration-time profile from time zero (0) to time = t (AUCt), the dosing interval, where t is 24 hours for anidulafungin and 12 hours for voriconazole. AM collected by bronchoscopy and BAL on Day 3. Summary parameters were derived using average data for all subjects and associated to a single subject for reporting purposes (mean with standard deviation was not calculated). | 4, 8, 12, 24 hours after start of infusion |
| AM: t1/2 | t1/2 = terminal elimination half-life in hours; Loge(2)Kel, where Kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. AM collected by bronchoscopy and BAL on Day 3. | 4, 8, 12, 24 hours after start of infusion |
| Overall Drug Penetration Ratio in ELF | ELF collected by bronchoscopy and BAL on Day 3. ELF to plasma penetration ratio calculated by dividing area under the plasma concentration-time profile (AUC) in ELF by AUC in plasma from 20 subjects where t is 24 hours for anidulafungin and 12 hours for voriconazole. Summary parameters were derived using average data for all subjects and associated to a single subject for reporting purposes (mean with standard deviation was not calculated). | 4, 8, 12, 24 hours after start of infusion |
| Concentration Ratio in ELF to Plasma | Concentration ratio in ELF to plasma determined by a point estimate within each subject at the time-point where ELF data was available. | 4, 8, 12, 24 hours after start of infusion |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
|
|
| Primary | Plasma PK: Time to Reach Maximum Plasma Concentration (Tmax) | Tmax = time (hours) to maximum plasma concentration (Cmax). Observed directly from data as time of first occurrence. Collected on Day 3. | PK parameter analysis population | Posted | Median | Full Range | hours | 100 minutes (end of infusion), 2, 4, 8, 12, 24 hours after start of infusion |
|
|
|
| Primary | Plasma PK: Area Under the Curve From Time Zero to Time = Tau (AUCtau) | AUCtau = area under the plasma concentration-time profile from time zero (0) to time = t (AUCt), the dosing interval, where t is 24 hours for anidulafungin and 12 hours for voriconazole; measured as micrograms times hours per milliliter (ug*hr/mL). Collected on Day 3. | PK parameter analysis population defined as all subjects randomized and treated who had at least 1 of the PK parameters of primary interest. | Posted | Mean | Standard Deviation | ug*hr/mL | 100 minutes (end of infusion), 2, 4, 8, 12, 24 hours after start of infusion |
|
|
|
| Primary | Plasma PK: Plasma Elimination Half-life (t1/2) | t1/2 = terminal elimination half-life in hours; Loge(2)/Kel, where Kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Collected on Day 3. | PK parameter analysis population; (n) = number of subjects contributing to the mean | Posted | Mean | Standard Deviation | hours | 100 minutes (end of infusion), 2, 4, 8, 12, 24 hours after start of infusion |
|
|
|
| Primary | Plasma PK: Total Clearance (CL Total) | CL total = total clearance calculated as dose divided by AUCt; measured as milliliters per minute (mL/min). Collected on Day 3. | PK parameter analysis population | Posted | Mean | Standard Deviation | mL/min | 100 minutes (end of infusion), 2, 4, 8, 12, 24 hours after start of infusion |
|
|
|
| Primary | Plasma PK: Volume of Distribution at Steady-state (Vss) | Vss = volume of distribution at steady-state; measured as liters (L). Calculated as (CL multiplied by mean residence time extrapolated to infinity [MRTinf]). MRTinf = [(AUMCt plus t (AUCinf minus AUCt)) divided by AUCt] minus (infusion time divided by 2); AUMCt = area under the first moment curve from time zero to time t; AUCinf = area under the plasma concentration-time curve extrapolated to infinity. | PK parameter analysis population; (n) = number of subjects contributing to the mean. | Posted | Mean | Standard Deviation | L | 100 minutes (end of infusion), 2, 4, 8, 12, 24 hours after start of infusion |
|
|
|
| Primary | Epithelial Lining Fluid (ELF) PK: Cmax | Cmax=maximum observed plasma concentration. ELF collected by bronchoscopy and bronchoalveolar lavage (BAL) Day 3; determined from BAL sample using urea dilution method: [Drug ELF]=[Drug BAL] multiplied by [Urea SERUM] divided by [Urea BAL]. Drug ELF=anidulafungin or voriconazole (drug) concentration in ELF corrected for dilution; Drug BAL=assayed drug concentration in BAL; Urea SERUM and Urea BAL simultaneously collected. Summary parameters derived using average data for all subjects; associated to a single subject for reporting purposes (mean with standard deviation not calculated). | PK parameter analysis population; summary parameters derived using average data for all subjects. | Posted | Number | average concentration (ug/mL) | 4, 8, 12, 24 hours after start of infusion |
|
|
|
| Primary | ELF PK: Tmax | Tmax = time (hours) to maximum plasma concentration (Cmax). Observed directly from data as time of first occurrence. ELF collected by bronchoscopy and BAL on Day 3. | PK parameter analysis population; summary parameters derived using average data for all subjects. | Posted | Number | hours | 4, 8, 12, 24 hours after start of infusion |
|
|
|
| Primary | ELF PK: AUCtau | AUCtau = area under the plasma concentration-time profile from time zero (0) to time = t (AUCt), the dosing interval, where t is 24 hours for anidulafungin and 12 hours for voriconazole. ELF collected by bronchoscopy and BAL on Day 3. Summary parameters were derived using average data for all subjects and associated to a single subject for reporting purposes (mean with standard deviation was not calculated). | PK parameter analysis population; summary parameters derived using average data for all subjects. | Posted | Number | average concentration (ug*hr/mL) | 4, 8, 12, 24 hours after start of infusion |
|
|
|
| Primary | ELF PK: t1/2 | t1/2 = terminal elimination half-life in hours; Loge(2)/Kel, where Kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. ELF collected by bronchoscopy and BAL on Day 3. | PK parameter analysis population; summary parameters derived using average data for all subjects. Data in ELF did not allow calculation of t1/2; not analyzed. | Posted | Number | hours | 4, 8, 12, 24 hours after start of infusion |
|
|
| Primary | Alveolar Macrophages (AM): Cmax | Cmax = maximum observed plasma concentration; observed directly from the data. AM collected by bronchoscopy and BAL on Day 3. Summary parameters were derived using average data for all subjects and associated to a single subject for reporting purposes (mean with standard deviation was not calculated). | PK parameter analysis population; summary parameters derived using average data for all subjects. | Posted | Number | average concentration (ug/mL) | 4, 8, 12, 24 hours after start of infusion |
|
|
|
| Primary | AM: Tmax | Tmax = time (hours) to maximum plasma concentration (Cmax). Observed directly from data as time of first occurrence. AM collected by bronchoscopy and BAL on Day 3. | PK parameter analysis population; summary parameters derived using average data for all subjects. | Posted | Number | hours | 4, 8, 12, 24 hours after start of infusion |
|
|
|
| Primary | AM: AUCtau | AUCtau = area under the plasma concentration-time profile from time zero (0) to time = t (AUCt), the dosing interval, where t is 24 hours for anidulafungin and 12 hours for voriconazole. AM collected by bronchoscopy and BAL on Day 3. Summary parameters were derived using average data for all subjects and associated to a single subject for reporting purposes (mean with standard deviation was not calculated). | PK parameter analysis population; summary parameters derived using average data for all subjects. | Posted | Number | average concentration (ug*hr/mL) | 4, 8, 12, 24 hours after start of infusion |
|
|
|
| Primary | AM: t1/2 | t1/2 = terminal elimination half-life in hours; Loge(2)Kel, where Kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. AM collected by bronchoscopy and BAL on Day 3. | PK parameter analysis population; summary parameters derived using average data for all subjects. Data in AM did not allow calculation of t1/2; not analyzed. | Posted | Number | hours | 4, 8, 12, 24 hours after start of infusion |
|
|
| Primary | Overall Drug Penetration Ratio in ELF | ELF collected by bronchoscopy and BAL on Day 3. ELF to plasma penetration ratio calculated by dividing area under the plasma concentration-time profile (AUC) in ELF by AUC in plasma from 20 subjects where t is 24 hours for anidulafungin and 12 hours for voriconazole. Summary parameters were derived using average data for all subjects and associated to a single subject for reporting purposes (mean with standard deviation was not calculated). | PK parameter analysis population; summary parameters derived using average data for all subjects. | Posted | Number | average ELF to plasma ratio | 4, 8, 12, 24 hours after start of infusion |
|
|
|
| Primary | Concentration Ratio in ELF to Plasma | Concentration ratio in ELF to plasma determined by a point estimate within each subject at the time-point where ELF data was available. | PK parameter analysis population; summary parameters derived using average data for all subjects. Subjects randomized to a single BAL procedure timepoint; bronchoscopy and BAL done for 5 different subjects at each timepoint. | Posted | Mean | Standard Deviation | ratio | 4, 8, 12, 24 hours after start of infusion |
|
|
|
| 0 |
| 21 |
| 15 |
| 21 |
| Visual impairment | Eye disorders | MedDRA (12.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
|
| Influenza like illness | General disorders | MedDRA (12.0) | Systematic Assessment |
|
| Hypersensitivity | Immune system disorders | MedDRA (12.0) | Systematic Assessment |
|
| Liver function test abnormal | Investigations | MedDRA (12.0) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (12.0) | Systematic Assessment |
|
| Hallucination, visual | Psychiatric disorders | MedDRA (12.0) | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA (12.0) | Systematic Assessment |
|
| Phlebitis | Vascular disorders | MedDRA (12.0) | Systematic Assessment |
|
Pfizer has the right to review disclosures, requesting a delay of < 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), < 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
| D000072742 |
| Invasive Fungal Infections |
| D016469 | Fungemia |
| D018805 | Sepsis |
| D018746 | Systemic Inflammatory Response Syndrome |
| D007249 | Inflammation |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D014230 |
| Triazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| Title | Measurements |
|---|---|
|
| Anidulafungin 24 hours |
|
| Voriconazole 4 hours |
|
| Voriconazole 8 hours |
|
| Voriconazole 12 hours |
|