Drug-Drug Interaction Between Rifampin and Fluvastatin

Drug-drug Interaction Clinical Trial

Official title:

The Effects of Single Dose Rifampin on Pharmacokinetics of Fluvastatin in Uninduced and Hepatically Induced Healthy Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04029584
• Other study ID #: 18-27008
• Status: Completed
• Phase: Phase 4
• Start date: April 25, 2019
• Est. completion date: April 25, 2020

Study information

• Verified date: August 2021
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: April 25, 2020
• Est. primary completion date: April 25, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. 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.

2. 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.

3. 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.

4. 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.

5. 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).

6. BMI between 18.0 - 30 kg/m2 o Subjects capable of fasting from food and beverages at least 8 hours prior to medication dosing.

7. Be able to read, speak, and understand English.

8. Subjects capable of providing informed consent and completing the requirements of the study.

Exclusion Criteria:

1. Subjects with active medical problems

2. Subjects on chronic prescription or over the counter (OTC) medication that cannot be stopped 2 weeks prior to and during the study.

3. Subjects incapable of multiple blood draws (HCT < 30mg/dL)

4. Subjects with a history of rhabdomyolysis

5. Subjects with a history of drug-related myalgias

6. Subjects with a history or diagnosis of hemorrhagic tendencies or blood dyscrasias

7. Subjects with a history of GI bleed or peptic ulcer disease

8. Subjects who smoke tobacco or have ongoing alcohol or illegal drug use

9. Subjects who are pregnant, lactating, or trying to conceive during the study period

10. Subjects allergic to fluvastatin or rifampin or any known component of the medications

11. Anyone who in the opinion of the study investigators is unable to do the study

Related Conditions & MeSH terms

• Drug-drug Interaction

Intervention

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

Locations

Country	Name	City	State
United States	University of California San Francisco	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
University of California, San Francisco

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	AUC	The primary outcome will be fluvastatin Area under the concentration vs time curve (AUC0-12h and AUC0-INF)	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	Cmax	Secondary outcomes will include fluvastatin maximum plasma concentration (Cmax).	Cmax will be assessed over a 12 hour study period.
Secondary	Tmax	Secondary outcomes will include time to Cmax (Tmax).	Tmax will be assessed over a 12 hour study period.