Trial Outcomes & Findings for Pharmacokinetics of Voriconazole in Obese Subjects (NCT NCT01030653)

Last Updated: 2017-02-09

Results Overview

Cmax is the maximum concentration, and Cmin is the minimum concentration. These measurements are based on analysis of plasma. The units shown are milligrams of voriconazole per liter of plasma. The two dosing regimens are: 1. a loading dose (400 mg x 2 doses, day 1) and maintenance doses (200 mg every 12 hours x 7 doses) in obese subjects. 2. a loading dose (400 mg x 2 doses, day 1) and maintenance doses (300 mg every 12 hours x 7 doses) in obese subjects.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

10 participants

Primary outcome timeframe

Day 5

Results posted on

2017-02-09

Participant Flow

Clinical research unit, subjects recruited over a 6 month period

This was a healthy volunteer study that did not require any pre assignment study procedures. 10 participants were consented but 8 were sufficient to complete the study. The remaining two subjects were not assigned to any arm, comparable to a screen failure. No intervention other than consent and screening occurred for these two subjects.

Participant milestones

Participant milestones
Measure	Voriconazole High Dose First Then Low Dose Active: Voriconazole Administered by Mouth as a Loading Dose (400 mg x 2 Doses, Day 1) and as Two Fixed Maintenance Doses ( 300 mg Every 12 Hours x 7 Doses) followed by a 7-day washout period then a Loading Dose (400 mg x 2 Doses, Day 1) and as Maintenance Doses ( 200 mg Every 12 Hours x 7 Doses)	Voriconazole Low Dose First Then High Dose Active: Voriconazole Administered by Mouth as a Loading Dose (400 mg x 2 Doses, Day 1) and as Two Fixed Maintenance Doses ( 200 mg Every 12 Hours x 7 Doses) followed by a 7-day washout period then a Loading Dose (400 mg x 2 Doses, Day 1) and as Maintenance Doses ( 300 mg Every 12 Hours x 7 Doses)
Loading Dose & First Maintenance Regimen STARTED	4	4
Loading Dose & First Maintenance Regimen COMPLETED	4	4
Loading Dose & First Maintenance Regimen NOT COMPLETED	0	0
7-Day Washout Period STARTED	4	4
7-Day Washout Period COMPLETED	4	4
7-Day Washout Period NOT COMPLETED	0	0
Loading Dose & 2nd Maintenance Regimen STARTED	4	4
Loading Dose & 2nd Maintenance Regimen COMPLETED	4	4
Loading Dose & 2nd Maintenance Regimen NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Pharmacokinetics of Voriconazole in Obese Subjects

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Voriconazole High Dose First Then Low Dose n=4 Participants Both voriconazole arms are shown as a single group because the same individuals received both arms of the intervention in a cross-over design.	Voriconazole Low Dose First Then High Dose n=4 Participants	Total n=8 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Gender Female	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Gender Male	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment United States	4 participants n=5 Participants	4 participants n=7 Participants	8 participants n=5 Participants

PRIMARY outcome

Timeframe: Day 5

Population: The same subjects were analyzed in a cross-over design at two dose levels

Outcome measures

Outcome measures
Measure	Voriconazole Lower Dose n=8 Participants Voriconazole Administered by Mouth as a Loading Dose (400 mg x 2 Doses, Day 1) and as Maintenance Doses (200 mg or Every 12 Hours x 7 Doses)	Voriconazole Higher Dose n=8 Participants Voriconazole Administered by Mouth as a Loading Dose (400 mg x 2 Doses, Day 1) and as Maintenance Doses (300 mg or Every 12 Hours x 7 Doses)
Steady-State Cmax and Cmin of Two Voriconazole Dosing Regimens Cmax	2.36 mg/L Interval 1.7 to 3.28	4.16 mg/L Interval 2.76 to 6.27
Steady-State Cmax and Cmin of Two Voriconazole Dosing Regimens Cmin	0.81 mg/L Interval 0.46 to 1.44	1.76 mg/L Interval 1.17 to 2.66

PRIMARY outcome

Timeframe: 14 days

Population: This is a comparison of the same group analyzed through a cross-over design of two voriconazole dosing regimens

AUC is the area under the concentration-time curve. The Geometric Mean Ratio and 90% confidence interval around this value permit an assessment of the bioequivalence of two dosing regimens in the same group. The geometric mean is computed based on the ratio of the AUC value from the high dose compared to the AUC value from the low dose for each individual. This ratio provides a more robust interpretation of the differences between the two dosing arms because each individual serves as their own control.

Outcome measures

Outcome measures
Measure	Voriconazole Lower Dose n=8 Participants Voriconazole Administered by Mouth as a Loading Dose (400 mg x 2 Doses, Day 1) and as Maintenance Doses (200 mg or Every 12 Hours x 7 Doses)	Voriconazole Higher Dose Voriconazole Administered by Mouth as a Loading Dose (400 mg x 2 Doses, Day 1) and as Maintenance Doses (300 mg or Every 12 Hours x 7 Doses)
Geometric Mean Ratio of the AUC Between the High and Low Dose Voriconazole	2 Ratio Interval 1.5 to 2.7	—

SECONDARY outcome

Timeframe: 12 hours

Outcome measures

Outcome measures
Measure	Voriconazole Lower Dose n=8 Participants Voriconazole Administered by Mouth as a Loading Dose (400 mg x 2 Doses, Day 1) and as Maintenance Doses (200 mg or Every 12 Hours x 7 Doses)	Voriconazole Higher Dose n=8 Participants Voriconazole Administered by Mouth as a Loading Dose (400 mg x 2 Doses, Day 1) and as Maintenance Doses (300 mg or Every 12 Hours x 7 Doses)
The Area Under the Curve Over the Dosing Interval for All Participants While on the High Dose and Low Dose Interventions.	14.6 hour*milligram/Liter Interval 9.21 to 23.1	29.2 hour*milligram/Liter Interval 19.4 to 43.8

Adverse Events

Voriconazole High Dose

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Voriconazole Low Dose

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Manjuanth Pai

University of Michigan

Phone: 7346470006

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place