The Effects of Rifampin on the Pharmacokinetics of Rosuvastatin

The Effects of Single-Dose Rifampin on the Pharmacokinetics of Rosuvastatin in Healthy White and Asian Volunteers

The effect of transporter inhibition by rifampin on the pharmacokinetics of rosuvastatin will be studied in clinical trial in White and Asian healthy volunteers.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Rosuvastatin; Drug: Rosuvastatin plus rifampin

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • CTSI Clinical Research Center, UCSF

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy Asian volunteers of Han-Chinese/Japanese/Korean descent whose parents and grandparents are Han-Chinese/ Japanese/ Korean.
• Healthy Caucasian volunteers of White/Caucasian/European-born descent whose parents and grandparents are White/Caucasian/European.
• 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 with the following genotype: SLCO1B1*1a and ABCG2 421CC.
• Subjects able to maintain adequate birth control during the study independent of hormonal contraceptive use.
• 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
• BMI between 18.0 - 30 kg/m2
• 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:

• Subjects with active medical problems
• Subjects on chronic prescription or 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 rosuvastatin 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Rosuvastatin	Drug: Rosuvastatin; Rosuvastatin 20mg po x1; Other Names: Crestor
Experimental: Rifampin plus rosuvastatin	Drug: Rosuvastatin plus rifampin; Rifampin 600mg IV infused over 30 minutes followed by rosuvastatin 20mg PO x1; Other Names: Crestor; Rifampicin; Rifadin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area-under-the-concentration curve (AUC) of rosuvastatin	Blood samples collected over a 48 hour period

Secondary Outcome Measures

Outcome Measure	Time Frame
Maximum plasma concentration (Cmax) of rosuvastatin	0, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 24, 32, and 48 hours post-dose
Time to concentration maximum (Tmax) of rosuvastatin	0, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 24, 32, and 48 hours post-dose

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Investigators: Principal Investigator: Leslie Z Benet, PhD, University of California, San Francisco; Principal Investigator: Lynda Frassetto, M.D., University of California, San Francisco

Study record dates

Study Major Dates

• Study Start: November 1, 2014
• Primary Completion (Actual): August 7, 2016
• Study Completion (Actual): August 7, 2016

Study Registration Dates

• First Submitted: April 3, 2014
• First Submitted That Met QC Criteria: April 7, 2014
• First Posted (Estimate): April 8, 2014

Study Record Updates

• Last Update Posted (Actual): January 23, 2020
• Last Update Submitted That Met QC Criteria: January 21, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: healthy volunteer; pharmacokinetics; drug interaction; Asian; rosuvastatin; rifampin; White; drug transporter
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Anti-Bacterial Agents; Leprostatic Agents; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Antitubercular Agents; Antibiotics, Antitubercular; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C8 Inducers; Cytochrome P-450 CYP2C19 Inducers; Cytochrome P-450 CYP2C9 Inducers; Rosuvastatin Calcium; Rifampin
• Other Study ID Numbers: 14-12970