Trial Outcomes & Findings for Drug Interaction Study of Rifampin and Warfarin in Healthy Volunteers. (NCT NCT00777855)

Last Updated: 2013-07-17

Results Overview

Uptake effects on warfarin pharmacokinetics during time period of hepatic organic anion-transporting polypeptide (OATP) inhibition by rifampin. Blood collection 1, 2, 4, 6, 8, and 12 hours after warfarin dosing.

Recruitment status

COMPLETED

Study phase

Target enrollment

10 participants

Primary outcome timeframe

0-12 hours after warfarin dosing

Results posted on

2013-07-17

Participant Flow

Healthy non-smoking volunteers from community

All participants were medication free throughout study enrollment

Participant milestones

Participant milestones
Measure	Warfarin First, Then Warfarin+Rifampin In a randomized, single-dose, two-period, crossover design, 5 participants received warfarin alone 7.5mg po; after a minimum of 14 days, participants received a 30-minute IV infusion of 600mg rifampin immediately followed by warfarin 7.5mg po.	Warfarin+Rifampin First, Then Warfarin Alone In a randomized, single-dose, two-period, crossover design, 5 participants received a 30-minute IV infusion of 600mg rifampin immediately followed by warfarin 7.5mg po; after a minimum of 14 days, participants received warfarin alone 7.5mg po.
First Intervention STARTED	5	5
First Intervention COMPLETED	5	5
First Intervention NOT COMPLETED	0	0
Washout Period (>= 14 Days) STARTED	5	5
Washout Period (>= 14 Days) COMPLETED	5	5
Washout Period (>= 14 Days) NOT COMPLETED	0	0
Second Intervention STARTED	5	5
Second Intervention COMPLETED	5	5
Second Intervention NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Drug Interaction Study of Rifampin and Warfarin in Healthy Volunteers.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Entire Study Population n=10 Participants Includes participants randomized to receive warfarin alone then warfarin+rifampin, and those randomized to receive warfarin+rifampin then warfarin alone in the crossover design
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	10 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age Continuous	30.1 years STANDARD_DEVIATION 9.9 • n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants
Region of Enrollment United States	10 participants n=5 Participants

PRIMARY outcome

Timeframe: 0-12 hours after warfarin dosing

Population: Each of 10 participants received both treatments separated by a minimum of 14 days; treatment sequence was randomly assigned

Outcome measures

Outcome measures
Measure	Warfarin n=10 Participants warfarin : warfarin 7.5mg po x 1	Warfarin Plus Rifampin n=10 Participants warfarin plus rifampin : warfarin 7.5mg po x 1 immediately following rifampin 600mg IV x 1
S- and R- Enantiomers of Warfarin (S-warfarin and R-warfarin) Area Under the Plasma Concentration-time Curve (AUC) From 0 to 12 Hours. AUC (0-12 hours) of R-warfarin	2,850 ng/ml*h Standard Deviation 460	2,930 ng/ml*h Standard Deviation 510
S- and R- Enantiomers of Warfarin (S-warfarin and R-warfarin) Area Under the Plasma Concentration-time Curve (AUC) From 0 to 12 Hours. AUC (0-12 hours) of S-warfarin	2,250 ng/ml*h Standard Deviation 340	2,230 ng/ml*h Standard Deviation 460

SECONDARY outcome

Timeframe: 0-120 hours after warfarin dosing

Population: Each of 10 participants received both treatments, in randomly assigned order, separated by a minimum of 14 days

Analysis of all concentration-time data. Blood collection 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours after warfarin dosing.

Outcome measures

Outcome measures
Measure	Warfarin n=10 Participants warfarin : warfarin 7.5mg po x 1	Warfarin Plus Rifampin n=10 Participants warfarin plus rifampin : warfarin 7.5mg po x 1 immediately following rifampin 600mg IV x 1
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity of S-warfarin and R-warfarin AUC(0-infinity) of S-warfarin	8,420 ng/ml*h Standard Deviation 1,090	7,410 ng/ml*h Standard Deviation 2,500
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity of S-warfarin and R-warfarin AUC(0-infinity) of R-warfarin	18,600 ng/ml*h Standard Deviation 3,400	14,100 ng/ml*h Standard Deviation 4,100

SECONDARY outcome

Timeframe: 0-120 hours after warfarin dosing

Population: Each of 10 participants received both treatments, in randomly assigned order, separated by a minimum of 14 days

Blood collection 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours after warfarin dosing.

Outcome measures

Outcome measures
Measure	Warfarin n=10 Participants warfarin : warfarin 7.5mg po x 1	Warfarin Plus Rifampin n=10 Participants warfarin plus rifampin : warfarin 7.5mg po x 1 immediately following rifampin 600mg IV x 1
Maximum Plasma Concentration (Cmax) of S-warfarin and R-warfarin Cmax of R-warfarin	375 ng/ml Standard Deviation 116	351 ng/ml Standard Deviation 85
Maximum Plasma Concentration (Cmax) of S-warfarin and R-warfarin Cmax of S-warfarin	329 ng/ml Standard Deviation 70	303 ng/ml Standard Deviation 82

Adverse Events

Entire Study Population

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

Leslie Benet

UCSF

Phone: (415) 476-3853

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place