Rosuvastatin Interethnic PK Study

NCT02215174 | Terminated Phase 1

• 2 other identifiers: 14-13695.14-13695
• Study Type: interventional
• Target: 21
• Locations: 2 countries
• Sites: 2

Brief Summary

Statins are the first-line and most commonly prescribed drugs for the prevention of cardiovascular diseases and stroke in the world. Our preliminary studies suggest that Caucasians might have a higher risk of developing potentially life-threatening drug-drug interactions than Asians when taking statins. Drug-drug interactions occur in the body when two or more drugs interact in a way that alters their effectiveness and/or toxicity. These interactions are becoming an increasingly severe problem with statin usage since patients at higher risk for cardiovascular diseases also take statins combined with many other drugs, such as antihypertensive and diabetic drugs. Our study is aimed at understanding the molecular factors and providing a sound basis for the interethnic dosage and response differences for statins. Drug-transporting proteins in intestine and liver tissues are responsible for taking up statins into the blood. It is hypothesized that there are interethnic function differences of these proteins and that they account for differences in statin blood levels between Caucasians and Asians and the frequency and/or severity of their respective drug-drug interactions. A clinical study will be conducted with Caucasian and Asian subjects undergoing gastric bypass surgery so excess intestine and liver tissue can be acquired as part of the standard procedure. Protein levels will be quantified in the tissues and correlate them with different statin blood levels.

Conditions

Statin Pharmacokinetics Pre and Post Gastric Bypass Surgery

Keywords

Rosuvastatin; PK; Interethnic; Morbid obese

Outcome Measures

Primary Outcomes (1)

• Area-under-the-concentration curve (AUC) of rosuvastatin

  0,1,2,3,4,5,6,8,12,24,36,48 hr post dosing

Secondary Outcomes (2)

• Change in oral clearance of rosuvastatin

  Pre-surgery period: 48 hr after dosing; post-surgery period: 48 hr after dosing. Two periods separated by at least two months.

• Descriptive comparison of messenger ribonucleic acid (mRNA) and protein expression in the tissues

  Day of the surgery

Study Arms (2)

Asians

EXPERIMENTAL

Drug: Rosuvastatin Rosuvastatin 20mg po x1 Other Name: Crestor

Drug: Rosuvastatin

Caucasians

EXPERIMENTAL

Drug: Rosuvastatin Rosuvastatin 20mg po x1 Other Name: Crestor

Drug: Rosuvastatin

Interventions

Rosuvastatin DRUG

Rosuvastatin 20mg po x1

Also known as: Crestor

Asians; Caucasians

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects that are scheduled for bariatric surgery.
• Subjects that are able and willing to donate surplus intestinal tissue.
• Subjects with solute carrier organic anion transporter \*1 (SLCO1B1) and breast cancer resistant protein (BCRP) 421CC genotypes.
• White/Caucasian/European and Asian/East Asian heritage individuals, male or female, 18 years of age or older.
• BMI between 30-55 kg/m2
• Be able to read, speak, and understand English(UCSF) and Chinese(Taiwan).
• Subjects capable of providing informed consent and completing the requirements of the study.

You may not qualify if:

• Subjects with active liver and kidney problems, severe cardiovascular diseases, type I diabetes, advanced pulmonary disease, and cancers.
• Subjects on chronic prescription or over the counter medication that have previously been reported to exhibit drug-drug interactions with rosuvastatin and cannot be stopped two weeks prior to and during the study, including gemfibrozil, cyclosporine, atazanavir, lopinavir and ritonavir.
• 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 with a recent history of trauma.
• 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 any known component of the medications.

Sponsors & Collaborators

• University of California, San Francisco: lead
• E-DA Hospital: collaborator

Study Sites (2)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

E-Da Hospital

Kaohsiung City, 82445, Taiwan

Location

Related Publications (1)

• Wu HF, Hristeva N, Chang J, Liang X, Li R, Frassetto L, Benet LZ. Rosuvastatin Pharmacokinetics in Asian and White Subjects Wild Type for Both OATP1B1 and BCRP Under Control and Inhibited Conditions. J Pharm Sci. 2017 Sep;106(9):2751-2757. doi: 10.1016/j.xphs.2017.03.027. Epub 2017 Apr 3.

  PMID: 28385543 DERIVED

MeSH Terms

Interventions

Rosuvastatin Calcium

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Leslie Benet, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 31, 2014
• First Posted: August 13, 2014
• Study Start: February 1, 2015
• Primary Completion: December 6, 2018
• Study Completion: December 6, 2018
• Last Updated: January 18, 2020

Record last verified: 2020-01

Locations

US (1); TW (1)