- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01497483
Drug-Drug Interaction Study With Pravastatin and Cyclosporine
The Pharmacokinetic Interaction Between Pravastatin and Cyclosporine in Healthy Volunteers
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Screening Procedures:
Prior to enrollment, subjects will be asked to come to the Clinical and Translational Science (CTSI) Clinical Research Center (CRC) at San Francisco General Hospital (SFGH). The study protocol and procedures will be explained in detail, all questions will be answered, and subjects will be provided with a consent form to sign. The screening visit will be conducted within 14 days of the first inpatient visit (i.e. first pravastatin with placebo or pravastatin with cyclosporine dosing day)
Only after subjects have consented to participate in the study will the screening procedures commence. During the screening visit, vital signs as well as blood sample (10 mL) will be taken by venipuncture to measure a complete blood count (CBC), electrolytes, blood urea nitrogen (BUN), creatinine, and liver function tests (LFTs) to screen for anemia and renal or hepatic insufficiency (see Inclusion/Exclusion Criteria)
Procedures During Main Study:
An equal number of subjects will be randomized, by a computer program, into one of the two study arms described below. On the first day of the study, subjects will be dosed with either 100 mg cyclosporine or placebo at 8PM, followed by an overnight fast. On the morning of Day 2, subjects will be asked to take a second dose of 100 mg cyclosporine or placebo at 8AM. At 9AM of Day 2, subjects will be asked to take 40 mg pravastatin. Plasma samples (5 ml) will be collected at baseline (prior to pravastatin administration), then at 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 10, 12 hours post-dose. Whole blood will also be collected 12 hours post-dose to measure the cyclosporine level.
The procedures during the second visit of the study will be identical to the first, but with dosing of 100 mg cyclosporine or placebo, opposite of what was dosed at the first study visit.
Clinical and Laboratory Determinations:
Analytical Methods:
Measurement of pravastatin in plasma will be performed by High Performance Liquid Chromatography (HPLC) with tandem mass spectrometry (MS/MS), using assays previously described and validated.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
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California
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San Francisco, California, United States, 94110
- San Francisco General Hosptail
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Carrier of one of the three SLCO1B1 polymorphisms that we are studying (SLCO1B1 521TT, 521TC, 521CC)
- Men or women (women must have negative pregnancy test)
- ages 18 to 45 years
- Caucasian
- Healthy, including no renal or hepatic disease, as determined from plasma creatinine and liver enzyme levels
- No medications currently, except for vitamins and oral contraceptive pills
- Willingness to spend two nights at the San Francisco General Hospital
- Sign informed consent
Exclusion Criteria:
- Under 18 years old
- Unable to confirm Caucasian ancestry
- Pregnant or lactating women (female subjects will have a urine pregnancy test at the screening visit)
- Prior history of allergic reaction to pravastatin or cyclosporine
- Has a risk of congestive heart failure requiring pharmacologic treatment (medical history)
- Has prior renal or hepatic dysfunction
- Risk of urinary or gastric retention or narrow-angle glaucoma (by medical history examination)
- Impaired renal function (e.g. as suggested by abnormal creatinine clearance, eGFR < 60 or serum creatinine > 1.4 mg/dl in females and > 1.5 mg/dl in males) which may also result from conditions such as cardiovascular collapse (shock), acute myocardial infarction (heart attack), and septicemia, abnormal heart rhythms (tachyarrhythmias; heart beat > 100 beats per minute)
- Impaired hepatic function (> 1.5 times the upper limit of normal)
- Evidence of anemia (hemoglobin <10g)
- Taking medications other than vitamins that could confound study results
- They do not provide informed consent to participate in the study
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Pravastatin alone
Subjects will be dosed with Pravastatin alone (40 mg)
|
Pravastatin 40 mg with placebo.
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Experimental: Pravastatin and Cyclosporine
Subjects will be dosed with pravastatin and cyclosporine.
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Pravastatin 40 mg co-administered with 200 mg of cyclosporine.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Composite of Pharmacokinetics of co-administration of pravastatin & cyclosporine in healthy volunteers
Time Frame: 24 hours
|
24 hours
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Deanna Kroetz, PhD, University of California, San Francisco
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Enzyme Inhibitors
- Antirheumatic Agents
- Antimetabolites
- Immunosuppressive Agents
- Immunologic Factors
- Dermatologic Agents
- Anticholesteremic Agents
- Hypolipidemic Agents
- Lipid Regulating Agents
- Hydroxymethylglutaryl-CoA Reductase Inhibitors
- Antifungal Agents
- Calcineurin Inhibitors
- Pravastatin
- Cyclosporine
- Cyclosporins
Other Study ID Numbers
- 11-06315
- U01GM061390 (U.S. NIH Grant/Contract)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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