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

A Phase 4, Open Label Study To Assess The Bronchopulmonary Pharmacokinetics Of Anidulafungin And Voriconazole Following Intravenous Administration In Healthy Subjects

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

Study Overview

• Status: Completed
• Conditions: Candidemia; Aspergillosis
• Intervention / Treatment: Drug: anidulafungin and voriconazole

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • Hartford, Connecticut, United States, 06102
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 1

Drug: anidulafungin and voriconazole; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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)	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

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (Actual): October 1, 2008
• Study Completion (Actual): October 1, 2008

Study Registration Dates

• First Submitted: July 13, 2009
• First Submitted That Met QC Criteria: July 14, 2009
• First Posted (Estimate): July 15, 2009

Study Record Updates

• Last Update Posted (Estimate): February 9, 2010
• Last Update Submitted That Met QC Criteria: January 5, 2010
• Last Verified: January 1, 2010

More Information

Terms related to this study

• Keywords: PK; fungal infection
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Bacterial Infections and Mycoses; Sepsis; Mycoses; Invasive Fungal Infections; Fungemia; Candidiasis; Candidiasis, Invasive; Candidemia; Aspergillosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Anidulafungin; Voriconazole
• Other Study ID Numbers: A8851020