CompletedNCT04029584Updated Sep 8, 2021Results posted

Drug-Drug Interaction Between Rifampin and Fluvastatin

A Phase 4 interventional study of rifampin IV and Rifadin 300Mg Capsule in Drug-drug Interaction, sponsored by University of California, San Francisco. Completed at 1 site in United States. Open to participants aged 18 Years to 65 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2021-09-08.

Sponsored by University of California, San Francisco · Phase 4, Interventional, and Basic science

Phase: Phase 4
Study type: Interventional
Enrollment: 10
Allocation: Randomized
Ages: 18 Years to 65 Years
Sex: All

Study summary

The effect of organic anion transporting polypeptide 1B1 (OATP1B1) transporter inhibition at clinical doses of fluvastatin, a biopharmaceutics drug disposition classification system (BDDCS) class 1 drug, has not been studied to date. A single dose of IV rifampin can be used as model OATP1B1 inhibitor to evaluate the significance of OATP1B1 transporter effects on fluvastatin disposition. A preinduction regimen of oral rifampin followed by a single IV infusion of rifampin can be used to evaluate the combined effects of enzyme induction and OATP1B1 transporter inhibition on fluvastatin disposition. A two arm, randomized, open label, crossover clinical study in healthy, volunteers will be conducted to evaluate the effects of IV rifampin on fluvastatin disposition in both hepatically induced and uninduced subjects.

Read the detailed description

The effect of rifampin on the pharmacokinetics of fluvastatin will be studied in healthy volunteers in a two arms, two-period, randomized, unblinded, crossover clinical trial. In the first arm, subjects will be randomized to one of two treatment groups:

(i)fluvastatin (Lescol®) 20mg capsule (ii) one oral dose of fluvastatin (Lescol®) 20mg capsule immediately following a 30-min intravenous infusion of rifampin 600mg in 10ml Normal Saline.

In the second arms, patients will be pretreated with 600mg oral rifampin (two 300mg rifadin capsule) once daily to induce hepatic enzymes (and transporters) for 5 years. Subjects will be randomized to one of two treatment groups:

(i) one oral dose of fluvastatin (Lescol®) 20mg capsule (ii) one oral dose of fluvastatin (Lescol®) 20mg capsule immediately following a 30-min intravenous infusion of rifampin 600mg in 10ml Normal Saline

Conditions studied

Drug-drug Interaction

Keywords

drug-drug interaction
statin
rifampin

In context

Lead sponsor

University of California, San Francisco is the lead sponsor of 2,132 studies on the registry; 375 are open to participants now.

Of its 262 completed or terminated interventional studies of FDA-regulated products, 196 (75%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 65 Years
Sexes eligible: All
Accepts healthy volunteers: Yes

Inclusion criteria

Healthy male or female, ages 18-65 years old, with no current medical conditions or active diagnoses as determined by the study doctor based on history, physical exam, and laboratory evaluations.
Subjects who take no other medications two weeks prior to the study and during the time course of the study including prescription medications, over-the-counter medications, dietary supplements, or drugs of abuse.
Subjects able to maintain adequate birth control during the study independent of hormonal contraceptives (including hormonal intrauterine devices (IUDs)). Adequate methods of contraception include use of condoms and copper IUDs.
Subjects able to abstain from grapefruit, grapefruit juice, oranges, orange juice, caffeinated beverages and/or alcoholic beverages from 7am the day before the study to completion of that study day.
Participants determined to have normal liver and kidney function as measured at baseline ( alanine aminotransferase (ALT): ≤ 2x upper level of normal (ULN), aspartate aminotransferase (AST): ≤ 2x ULN, serum creatinine (SCr): ≤ 1.5x ULN, T. Bili: 0.1-1.2mg/dL, Albumin: 3.4 - 4.7 mg/dL).
BMI between 18.0 - 30 kg/m2 o Subjects capable of fasting from food and beverages at least 8 hours prior to medication dosing.
Be able to read, speak, and understand English.
Subjects capable of providing informed consent and completing the requirements of the study.

Exclusion criteria

Exclusion Criteria:

Subjects with active medical problems
Subjects on chronic prescription or over the counter (OTC) medication that cannot be stopped 2 weeks prior to and during the study.
Subjects incapable of multiple blood draws (HCT \< 30mg/dL)
Subjects with a history of rhabdomyolysis
Subjects with a history of drug-related myalgias
Subjects with a history or diagnosis of hemorrhagic tendencies or blood dyscrasias
Subjects with a history of GI bleed or peptic ulcer disease
Subjects who smoke tobacco or have ongoing alcohol or illegal drug use
Subjects who are pregnant, lactating, or trying to conceive during the study period
Subjects allergic to fluvastatin or rifampin or any known component of the medications
Anyone who in the opinion of the study investigators is unable to do the study

Study design

Phase: Phase 4
Primary purpose: Basic science
Allocation: Randomized
Intervention model: Crossover assignment
Masking: None (open label)
Enrollment: 10 participants (actual)

Study arms

Experimental
Fluvastatin Alone First, Then Fluvastatin +IV Rifampin 600 mg
The effect of rifampin on the pharmacokinetics of fluvastatin will be studied in healthy volunteers with or without hepatic induction in a randomized, unblinded, crossover clinical trial. For uninduced periods, subjects will be randomized to receive one oral dose of fluvastatin (Lescol®) 20mg capsule first. Separated by one day of washout, they then receive one oral dose of fluvastatin (Lescol®) 20mg capsule immediately following a 30-min intravenous infusion of rifampin 600mg in 10ml Normal Saline. Before starting hepatic induced period, subjects will have a washout for greater than one week. To induce hepatic enzyme and transporter, Subjects will be pretreated with 5 days with 600mg oral rifampin. Subjects will be then randomized first to receive a single dose of fluvastatin 20mg. Separated by one day of washout, subject will then receive one oral dose of fluvastatin 20mg immediately after a 30-min IV infusion of rifampin 600mg.
Drug: rifampin IV · Drug: Rifadin 300Mg Capsule · Drug: Fluvastatin 20 MG
Experimental
Fluvastatin +IV Rifampin 600 mg First, Then Fluvastatin Alone
The effect of rifampin on the disposition of fluvastatin will be studied in healthy volunteers with or without hepatic induction in a randomized, unblinded, crossover clinical trial. For uninduced periods, subjects will be randomized to first receive one oral dose of fluvastatin (Lescol®) 20mg capsule immediately following a 30-min intravenous infusion of rifampin 600mg in 10ml Normal Saline.Separated by one day of washout, subjects will be then receive a single dose of fluvastatin (Lescol®) 20mg capsule. Before starting induction periods, subjects will have a washout greater than one week. To induce hepatic enzyme and transporter, subjects will be pretreated with 5 days with 600mg oral rifampin. subjects will be randomized to receive first one oral dose of fluvastatin 20mg immediately after a 30-min IV infusion of rifampin 600mg. Separated by one day of washout, subject will then receive one oral dose of fluvastatin 20mg.
Drug: rifampin IV · Drug: Rifadin 300Mg Capsule · Drug: Fluvastatin 20 MG

Interventions

Drugrifampin IV
A 30-min intravenous infusion of rifampin 600mg in 10ml Normal Saline will be used to inhibit hepatic OATP1B1 transporters.
DrugRifadin 300Mg Capsule
Rifadin 600mg by mouth as two 300mg rifadin capsules
DrugFluvastatin 20 MG
one oral dose of fluvastatin (Lescol ) 20mg capsule

What researchers measure

Primary outcomes

AUC
The primary outcome will be fluvastatin Area under the concentration vs time curve (AUC0-12h and AUC0-INF)
Time frame: AUC will be assessed over a 12 hour study at 0, 0.33, 0.67,1,1.5, 2, 2.5, 3, 4, 6, 9, 12h

Secondary outcomes

Cmax
Secondary outcomes will include fluvastatin maximum plasma concentration (Cmax).
Time frame: Cmax will be assessed over a 12 hour study period.
Tmax
Secondary outcomes will include time to Cmax (Tmax).
Time frame: Tmax will be assessed over a 12 hour study period.

Results

Posted Sep 8, 2021

Participant flow

Flyer on campus and Craiglist

Uninduced Study 1st Intervention (1 Day)

Participant flow — Uninduced Study 1st Intervention (1 Day)
Milestone	Fluvastatin Alone First, Then Fluvastatin +IV Rifampin 600 mg	Fluvastatin +IV Rifampin 600 mg First, Then Fluvastatin Alone
Started	4	6
Completed	4	6
Not completed	0	0

Uninduced Washout (1 Day)

Participant flow — Uninduced Washout (1 Day)
Milestone	Fluvastatin Alone First, Then Fluvastatin +IV Rifampin 600 mg	Fluvastatin +IV Rifampin 600 mg First, Then Fluvastatin Alone
Started	4	6
Completed	4	6
Not completed	0	0

Uninduced Study 2nd Intervention (1 Day)

Participant flow — Uninduced Study 2nd Intervention (1 Day)
Milestone	Fluvastatin Alone First, Then Fluvastatin +IV Rifampin 600 mg	Fluvastatin +IV Rifampin 600 mg First, Then Fluvastatin Alone
Started	4	6
Completed	4	6
Not completed	0	0

Washout Between (>1 Week)

Participant flow — Washout Between (>1 Week)
Milestone	Fluvastatin Alone First, Then Fluvastatin +IV Rifampin 600 mg	Fluvastatin +IV Rifampin 600 mg First, Then Fluvastatin Alone
Started	4	6
Completed	4	6
Not completed	0	0

Induced Study 1st Intervention (1 Day)

Participant flow — Induced Study 1st Intervention (1 Day)
Milestone	Fluvastatin Alone First, Then Fluvastatin +IV Rifampin 600 mg	Fluvastatin +IV Rifampin 600 mg First, Then Fluvastatin Alone
Started	2	8
Completed	2	8
Not completed	0	0

Induced Washout (1 Day)

Participant flow — Induced Washout (1 Day)
Milestone	Fluvastatin Alone First, Then Fluvastatin +IV Rifampin 600 mg	Fluvastatin +IV Rifampin 600 mg First, Then Fluvastatin Alone
Started	2	8
Completed	2	8
Not completed	0	0

Induced Study 2nd Intervention (1 Day)

Participant flow — Induced Study 2nd Intervention (1 Day)
Milestone	Fluvastatin Alone First, Then Fluvastatin +IV Rifampin 600 mg	Fluvastatin +IV Rifampin 600 mg First, Then Fluvastatin Alone
Started	2	8
Completed	2	8
Not completed	0	0

Outcome measures

PrimaryAUC

The primary outcome will be fluvastatin Area under the concentration vs time curve (AUC0-12h and AUC0-INF)

Time frame:: AUC will be assessed over a 12 hour study at 0, 0.33, 0.67,1,1.5, 2, 2.5, 3, 4, 6, 9, 12h
Reported as:: Mean · ng/mL·h

AUC
ng/mL·h	Fluvastatin Control	Fluvastatin and IV Rifampin	Fluvastatin + Oral Rifampin Induction	Fluvastatin +Oral Rifampin Induced +IV Rifampin
AUC(0-12)	242 ± 83	642 ± 269	124 ± 33.7	371 ± 217
AUC(0-INF)	266 ± 86	679 ± 274	136 ± 35.9	385 ± 222

SecondaryCmax

Secondary outcomes will include fluvastatin maximum plasma concentration (Cmax).

Time frame:: Cmax will be assessed over a 12 hour study period.
Reported as:: Mean · ng/mL

Cmax
ng/mL	Fluvastatin Control	Fluvastatin and IV Rifampin	Fluvastatin + Oral Rifampin Induction	Fluvastatin +Oral Rifampin Induced +IV Rifampin
Cmax	176 ± 149	447 ± 342	87.8 ± 37.3	379 ± 446

SecondaryTmax

Secondary outcomes will include time to Cmax (Tmax).

Time frame:: Tmax will be assessed over a 12 hour study period.
Reported as:: Mean · hr

Tmax
hr	Fluvastatin Control	Fluvastatin and IV Rifampin	Fluvastatin + Oral Rifampin Induction	Fluvastatin +Oral Rifampin Induced +IV Rifampin
Tmax	1.20 ± 0.62	1.17 ± 0.72	1.28 ± 0.545	1.23 ± 0.960

Adverse events

Collected over Adverse event was monitored in uninduced arm from study day 1 to day 3. Adverse event was monitored in induced arm from study day -5 to day 3.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Uninduced Healthy Volunteer Fluvastatin Alone	0/10 (0%)	0/10 (0%)	0/10 (0%)
Uninduced Healthy Volunteer Fluvastatin and Rifampin	0/10 (0%)	0/10 (0%)	0/10 (0%)
Hepatic Induced Healthy Volunteer Fluvastatin Alone	0/10 (0%)	0/10 (0%)	0/10 (0%)
Hepatic Induced Healthy Volunteer Fluvastatin and Rifampin	0/10 (0%)	0/10 (0%)	0/10 (0%)

Baseline characteristics

Healthy volunteers

Age, Continuous
Age, Continuous(years)	All Subjects
Mean	38 ± 13

Sex: Female, Male
Sex: Female, Male(Participants)	All Subjects
Female	4
Male	6

Race/Ethnicity, Customized
Race/Ethnicity, Customized(participants)	All Subjects
Caucasian	4
African American	2
Asian	2
Hispanic	2

Region of Enrollment
Region of Enrollment(participants)	All Subjects
United States	10

Serum creatinine
Serum creatinine(mg/dL)	All Subjects
Mean	0.79 ± 0.13

Study locations

1 site

University of California San Francisco
San Francisco, California 94143, United States

References and documents

Study documents

Protocol and statistical analysis plan · Apr 26, 2019
Informed consent form · Dec 26, 2018

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No — All study data will be stored and analyzed at University of California San Francisco (UCSF) by the Principal investigator and Key Study personnel. There are no plans of sharing the subjects data with any outside entities.

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Sep 8, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT04029584
Lead sponsor: University of California, San Francisco
Responsible party: Sponsor
First posted: Jul 23, 2019
Start date: Apr 25, 2019
Primary completion: Apr 25, 2020
Completion: Apr 25, 2020
Results posted: Sep 8, 2021
Last update: Sep 8, 2021

Study contacts

Leslie Benet, PhD

principal investigator · University of California, San Francisco

Oversight

Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Aug 2021. You cannot join it, but the record below documents what was studied.

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