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

NCT00940017 | Completed Phase 4 Results

• 1 other identifier: A8851020
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Aspergillosis; Candidemia

Keywords

PK; fungal infection

Outcome Measures

Primary Outcomes (16)

• 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

Study Arms (1)

1

EXPERIMENTAL

Drug: anidulafungin and voriconazole

Interventions

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.

1

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy adult subjects willing to comply with the study requirement.

You may not qualify if:

• Clinical significant disease.
• Sensitive to study medication.
• Not willing to comply with the study requirement.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (1)

Pfizer Investigational Site

Hartford, Connecticut, 06102, United States

Location

Related Links

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

MeSH Terms

Conditions

Aspergillosis; Candidemia; Mycoses

Interventions

Anidulafungin; Voriconazole

Condition Hierarchy (Ancestors)

Bacterial Infections and Mycoses; Infections; Candidiasis, Invasive; Candidiasis; Invasive Fungal Infections; Fungemia; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Echinocandins; Peptides, Cyclic; Peptides; Amino Acids, Peptides, and Proteins; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.govCallCenter@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: July 13, 2009
• First Posted: July 15, 2009
• Study Start: September 1, 2008
• Primary Completion: October 1, 2008
• Study Completion: October 1, 2008
• Last Updated: February 9, 2010
• Results First Posted: February 9, 2010

Record last verified: 2010-01

Locations

US (1)