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A Study To Assess The Anidulafungin And Voriconazole Concentration In Lung Following Intravenous Administration In Healthy Subjects

Phase 4
Completed
Conditions
Aspergillosis
Candidemia
Interventions
Registration Number
NCT00940017
Lead Sponsor
Pfizer
Brief Summary

The purpose of this study is to provide anidulafungin and voriconazole to healthy subjects to determine the drug concentration in the lung.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
24
Inclusion Criteria
  • Healthy adult subjects willing to comply with the study requirement.
Exclusion Criteria
  • Clinical significant disease.
  • Sensitive to study medication.
  • Not willing to comply with the study requirement.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
1anidulafungin and voriconazole-
Primary Outcome Measures
NameTimeMethod
Plasma Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax)100 minutes (end of infusion), 2, 4, 8, 12, 24 hours after start of infusion

Cmax = maximum observed plasma concentration; measured in micrograms per milliliter (ug/mL). Observed directly from the data. Collected on Day 3.

Plasma PK: Time to Reach Maximum Plasma Concentration (Tmax)100 minutes (end of infusion), 2, 4, 8, 12, 24 hours after start of infusion

Tmax = time (hours) to maximum plasma concentration (Cmax). Observed directly from data as time of first occurrence. Collected on Day 3.

Plasma PK: Area Under the Curve From Time Zero to Time = Tau (AUCtau)100 minutes (end of infusion), 2, 4, 8, 12, 24 hours after start of infusion

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.

Plasma PK: Plasma Elimination Half-life (t1/2)100 minutes (end of infusion), 2, 4, 8, 12, 24 hours after start of infusion

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.

Plasma PK: Total Clearance (CL Total)100 minutes (end of infusion), 2, 4, 8, 12, 24 hours after start of infusion

CL total = total clearance calculated as dose divided by AUCt; measured as milliliters per minute (mL/min). Collected on Day 3.

Plasma PK: Volume of Distribution at Steady-state (Vss)100 minutes (end of infusion), 2, 4, 8, 12, 24 hours after start of infusion

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.

Epithelial Lining Fluid (ELF) PK: Cmax4, 8, 12, 24 hours after start of infusion

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).

ELF PK: Tmax4, 8, 12, 24 hours after start of infusion

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.

ELF PK: AUCtau4, 8, 12, 24 hours after start of infusion

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).

ELF PK: t1/24, 8, 12, 24 hours after start of infusion

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.

Alveolar Macrophages (AM): Cmax4, 8, 12, 24 hours after start of infusion

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).

AM: Tmax4, 8, 12, 24 hours after start of infusion

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.

AM: AUCtau4, 8, 12, 24 hours after start of infusion

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).

AM: t1/24, 8, 12, 24 hours after start of infusion

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.

Overall Drug Penetration Ratio in ELF4, 8, 12, 24 hours after start of infusion

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).

Concentration Ratio in ELF to Plasma4, 8, 12, 24 hours after start of infusion

Concentration ratio in ELF to plasma determined by a point estimate within each subject at the time-point where ELF data was available.

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

Pfizer Investigational Site

🇺🇸

Hartford, Connecticut, United States

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