Drug-Drug Interaction Study With Pravastatin and Cyclosporine

NCT01497483 | Completed Phase 1 DMC

• 2 other identifiers: 11-06315U01GM061390
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

This study will address the following question: Does cyclosporine affect the pharmacokinetics of pravastatin in healthy volunteers? Studies have shown that cyclosporine inhibits the organic anion transporter required for pravastatin transport into the liver, thus increasing pravastatin levels in the blood. The investigators hypothesize that this inhibition will vary among people based on genetic differences. This knowledge is important to help develop safer and more effective drug therapy with reduced side effects.

Conditions

Healthy

Outcome Measures

Primary Outcomes (1)

• Composite of Pharmacokinetics of co-administration of pravastatin & cyclosporine in healthy volunteers

  24 hours

Study Arms (2)

Pravastatin alone

ACTIVE COMPARATOR

Subjects will be dosed with Pravastatin alone (40 mg)

Drug: Pravastatin alone

Pravastatin and Cyclosporine

EXPERIMENTAL

Subjects will be dosed with pravastatin and cyclosporine.

Drug: Pravastatin and Cyclosporine

Interventions

Pravastatin alone DRUG

Pravastatin 40 mg with placebo.

Pravastatin alone

Pravastatin and Cyclosporine DRUG

Pravastatin 40 mg co-administered with 200 mg of cyclosporine.

Pravastatin and Cyclosporine

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, San Francisco: lead
• National Institute of General Medical Sciences (NIGMS): collaborator

Study Sites (1)

San Francisco General Hosptail

San Francisco, California, 94110, United States

Location

MeSH Terms

Interventions

Pravastatin; Cyclosporine

Intervention Hierarchy (Ancestors)

Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Deanna Kroetz, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 7, 2011
• First Posted: December 22, 2011
• Study Start: December 1, 2011
• Primary Completion: May 1, 2013
• Study Completion: December 1, 2013
• Last Updated: January 16, 2015

Record last verified: 2015-01

Locations

US (1)