Statin Pharmacokinetics Pre and Post Gastric Bypass SurgeryPhase 1RSTNCT02215174
Rosuvastatin Interethnic PK Study
A Phase 1 study testing Rosuvastatin in people with Statin Pharmacokinetics Pre and Post Gastric Bypass Surgery, run by University of California, San Francisco at 2 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Statin Pharmacokinetics Pre and Post Gastric Bypass Surgery
- What is being tested?
- Rosuvastatin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 2 sitesin 2 countries
- Study dates
- Feb 2015to 6 Dec 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
United States1 site
University of California, San Francisco
San Francisco, California, 94143
About this study
Official title: Rosuvastatin Pharmacokinetic (PK) Study in Caucasian and Asian Morbid Obese Patients
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.
- Being tested
- Rosuvastatin
- Keywords
- Rosuvastatin, PK, Interethnic, Morbid obese
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RosuvastatinDrug
Also called Crestor
Rosuvastatin 20mg po x1
| Study group | Role | What they receive |
|---|---|---|
| Asians | Experimental | Drug: Rosuvastatin Rosuvastatin 20mg po x1 Other Name: Crestor Receives: Drug: Rosuvastatin |
| Caucasians | Experimental | Drug: Rosuvastatin Rosuvastatin 20mg po x1 Other Name: Crestor Receives: Drug: Rosuvastatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area-under-the-concentration curve (AUC) of rosuvastatin
Measured: 0,1,2,3,4,5,6,8,12,24,36,48 hr post dosing
Secondary outcomes (2)
Change in oral clearance of rosuvastatin
Changes in oral clearance of rosuvastatin within gastric bypass surgery will be analyzed using the ratio of areas under the systemic concentration curves (AUCs) from before to after surgery using the bioequivalence criteria of 80-125%. The oral clearance will be calculated based on the plasma data from each of the blood draws after the dosing period is completed (48hr). The pre and post surgery period are separated by at least a 8-week recovery period.
Measured: 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
Tissue samples will be collected on the day of the surgery.
Measured: Day of the surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Aug 2014 (estimated)
- Study startFeb 2015
- Primary completion6 Dec 2018
- Study completion6 Dec 2018
Why it stopped: IRB approval expired
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Statin Pharmacokinetics Pre and Post Gastric Bypass SurgeryStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- E-DA Hospital
- Responsible party
- Sponsor
- Investigators
- Leslie Benet, PhD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02215174
- Sponsor's protocol ID
- 14-13695.
- Other IDs
- 14-13695
- Acronym
- RST
- Status last verified
- Jan 2020
- First submitted
- 31 Jul 2014
- Last updated
- 18 Jan 2020
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 28385543
Study at a glance
From the registry record, last updated by the sponsor on 18 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Rosuvastatin Pharmacokinetic (PK) Study in Caucasian and Asian Morbid Obese Patients
- ClinicalTrials.gov ID
- NCT02215174
- Acronym / sponsor ID
- RST / 14-13695.
- Keywords
- Rosuvastatin, PK, Interethnic, Morbid obese
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: IRB approval expired
- Enrolment
- 21 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- E-DA Hospital
- Study start
- Feb 2015
- Primary completion
- 6 Dec 2018 (actual)
- Study completion
- 6 Dec 2018 (actual)
- First posted
- 13 Aug 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Asians | Experimental | Drug: RosuvastatinDrug: Rosuvastatin Rosuvastatin 20mg po x1 Other Name: Crestor |
| Caucasians | Experimental | Drug: RosuvastatinDrug: Rosuvastatin Rosuvastatin 20mg po x1 Other Name: Crestor |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RosuvastatinAlso: CrestorRosuvastatin 20mg po x1 | Drug | Asians, Caucasians |
Primary outcome
Area-under-the-concentration curve (AUC) of rosuvastatin
Time frame: 0,1,2,3,4,5,6,8,12,24,36,48 hr post dosing
2 secondary outcomes
Change in oral clearance of rosuvastatin
Time frame: 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
Time frame: Day of the surgery
Results and safety
The study was stopped early (reason given: IRB approval expired). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jan 2020.
- Derived from this study: PubMed 28385543Wu 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.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Leslie Benet, PhD principal investigator
University of California, San Francisco
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Rosuvastatin in people with Statin Pharmacokinetics Pre and Post Gastric Bypass Surgery, run by University of California, San Francisco at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 18 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States, Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: IRB approval expired). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area-under-the-concentration curve (AUC) of rosuvastatin (time frame: 0,1,2,3,4,5,6,8,12,24,36,48 hr post dosing). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02215174, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jan 2020.