Clinical trial NCT02215174: Rosuvastatin Interethnic PK Study
Official title: Rosuvastatin Pharmacokinetic (PK) Study in Caucasian and Asian Morbid Obese Patients
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Statin Pharmacokinetics Pre and Post Gastric Bypass Surgery
Keywords: Rosuvastatin
PK
Interethnic
Morbid obese
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: E-DA Hospital
First posted: 2014-08-13
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Area-under-the-concentration curve (AUC) of rosuvastatin
timeFrame: 0,1,2,3,4,5,6,8,12,24,36,48 hr post dosing
Secondary outcomes:
measure: Change in oral clearance of rosuvastatin
timeFrame: Pre-surgery period: 48 hr after dosing; post-surgery period: 48 hr after dosing. Two periods separated by at least two months.
measure: Descriptive comparison of messenger ribonucleic acid (mRNA) and protein expression in the tissues
timeFrame: Day of the surgery
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Kaohsiung
country: Taiwan
facility: E-Da Hospital
Study officials:
affiliation: University of California, San Francisco
name: Leslie Benet, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.