Trial Outcomes & Findings for To Determine The Amount Of Voriconazole In The Brain After 2 Loading Doses And 3 Maintenance Doses Over 3 Days (NCT NCT00300677)

Last Updated: 2009-10-14

Results Overview

Mean plasma voriconazole concentrations (nanograms per milliliter \[ng/mL\]) pre-dose (Cmin) and two hours post-dose (C2h). Plasma samples were assayed using a validated, sensitive, and specific high performance liquid chromatography/tandem mass spectrometry (HPLC-MS/MS) method.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

12 participants

Primary outcome timeframe

Day 3: pre-dose, 2 hours post-dose

Results posted on

2009-10-14

Participant Flow

Healthy male volunteers were recruited by 1 hospital center in the U.S. between March 2007 and August 2008.

Participant milestones

Participant milestones
Measure	Voriconazole 400 mg every 12 hours on Day 1; 200 mg every 12 hours on Day 2; 200 mg on Day 3
Overall Study STARTED	12
Overall Study COMPLETED	12
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

To Determine The Amount Of Voriconazole In The Brain After 2 Loading Doses And 3 Maintenance Doses Over 3 Days

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Voriconazole n=12 Participants 400 mg every 12 hours on Day 1; 200 mg every 12 hours on Day 2; 200 mg on Day 3
Age, Customized 18-25 years	3 participants n=5 Participants
Age, Customized 26-35 years	6 participants n=5 Participants
Age, Customized 36-45 years	3 participants n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 3: pre-dose, 2 hours post-dose

Population: Pharmacokinetic Analysis Set: subjects included in the statistical analysis of pharmacokinetic parameters had the pharmacokinetic parameter of interest. N=number of observations (non-missing concentrations).

Outcome measures

Outcome measures
Measure	Voriconazole n=12 Participants 400 mg every 12 hours on Day 1; 200 mg every 12 hours on Day 2; 200 mg on Day 3
Plasma Concentrations of Voriconazole predose (Cmin)	839.50 ng/mL Standard Deviation 874.22
Plasma Concentrations of Voriconazole 2 hours postdose (C2h)	2182.33 ng/mL Standard Deviation 1190.63

PRIMARY outcome

Timeframe: Day 3: pre-dose, 2 hours post-dose

Mean brain concentrations (ng/mL) of voriconazole pre-dose and 2 hours post-dose measured by Fluorine (F) Magnetic Resonance Spectroscopy (F-MRS).

Outcome measures

Outcome measures
Measure	Voriconazole n=12 Participants 400 mg every 12 hours on Day 1; 200 mg every 12 hours on Day 2; 200 mg on Day 3
Brain Concentrations of Voriconazole predose (Cmin)	2090.44 ng/mL Standard Deviation 1227.88
Brain Concentrations of Voriconazole 2 hours postdose (C2h)	4165.20 ng/mL Standard Deviation 1806.93

PRIMARY outcome

Timeframe: Day 3: pre-dose, 2 hours post-dose

Mean plasma concentrations of voriconazole N-oxide metabolite (ng/mL) pre-dose and 2 hours post-dose. Plasma samples were assayed using a validated, sensitive, and specific high performance liquid chromatography/tandem mass spectrometry (HPLC-MS/MS) method.

Outcome measures

Outcome measures
Measure	Voriconazole n=12 Participants 400 mg every 12 hours on Day 1; 200 mg every 12 hours on Day 2; 200 mg on Day 3
Plasma Concentrations of N-oxide Metabolite predose (Cmin)	3076.67 ng/mL Standard Deviation 841.96
Plasma Concentrations of N-oxide Metabolite 2 hours postdose (C2h)	3665.00 ng/mL Standard Deviation 958.73

PRIMARY outcome

Timeframe: Day 3: pre-dose, 2 hours post-dose

Mean brain concentrations (ng/mL) of voriconazole N-oxide metabolite pre-dose and 2 hours post-dose measured by Fluorine (F) Magnetic Resonance Spectroscopy (F-MRS).

Outcome measures

Outcome measures
Measure	Voriconazole n=12 Participants 400 mg every 12 hours on Day 1; 200 mg every 12 hours on Day 2; 200 mg on Day 3
Brain Concentrations of N-oxide Metabolite predose (Cmin)	663.97 ng/mL Standard Deviation 677.55
Brain Concentrations of N-oxide Metabolite 2 hours postdose (C2h)	1535.40 ng/mL Standard Deviation 1280.09

Adverse Events

Voriconazole

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Voriconazole n=12 participants at risk 400 mg every 12 hours on Day 1; 200 mg every 12 hours on Day 2; 200 mg on Day 3
Ear and labyrinth disorders Ear discomfort	8.3% 1/12
Eye disorders Dry eye	8.3% 1/12
Eye disorders Photophobia	41.7% 5/12
Eye disorders Vision blurred	25.0% 3/12
Gastrointestinal disorders Abdominal pain	8.3% 1/12
Gastrointestinal disorders Dry mouth	16.7% 2/12
Gastrointestinal disorders Nausea	8.3% 1/12
General disorders Fatigue	8.3% 1/12
General disorders Pain	8.3% 1/12
Infections and infestations Pharyngitis streptococcal	8.3% 1/12
Injury, poisoning and procedural complications Procedural dizziness	16.7% 2/12
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	8.3% 1/12
Nervous system disorders Dizziness	16.7% 2/12
Nervous system disorders Head discomfort	16.7% 2/12
Nervous system disorders Headache	33.3% 4/12
Nervous system disorders Paraesthesia	8.3% 1/12
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	8.3% 1/12
Skin and subcutaneous tissue disorders Cold sweat	8.3% 1/12

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
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Restriction type: OTHER