Drug-drug Interaction Study to Evaluate the Effect of ISIS 681257 on Clopidogrel

Study Overview
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Brief Summary
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This is a single center, open label, single sequence, two treatment, two-period drug-drug interaction study to evaluate the effect of multiple doses of ISIS 681257 on the pharmacokinetics of multiple doses of clopidogrel

Official Title
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Drug-Drug Interaction Study To Evaluate The Effect Of Multiple Doses Of ISIS 681257 40 mg Subcutaneous Injections On The Pharmacokinetics And Pharmacodynamics Of Clopidogrel In Healthy Subjects

Conditions
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Elevated Lipoprotein(a), Cardiovascular Diseases

Intervention / Treatment
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* Drug: ISIS 681257
* Drug: Clopidogrel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Motivated and available for duration of study and willing to adhere to protocol Males who are unable to procreate or agree to contraception throughout study Females who are postmenopausal or surgically sterile BMI between 18.5 and 30 kg/m2 Weighing greater than or equal to 50kg Normal lab results No known diseases or significant findings on physical exam Exclusion Criteria: Females of childbearing potential Reactions/infection at injection site Hypersensitivity to any drugs or similar drugs to those used in the study Conditions or disease that may interfere with study drug Any significant diseases Known history or familial history of bleeding disorders Drug dependency or abuse Illness within 28 days Previous exposure to other investigational drug within 28 days Blood donations within 28 days

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Clopidogrel Dosing<br>Multiple doses of Clopidogrel to obtain pharmacokinetic information. | Drug: Clopidogrel<br>* 75mg tablet administered orally<br>|
| Experimental: Clopidogrel in combination with ISIS 681257<br>Multiple doses of clopidogrel administered with 2 doses of ISIS 681257 at 2 individual timepoints to obtain pharmacokinetic information. | Drug: ISIS 681257<br>* Xmg dose administered as a subcutaneous injection<br>Drug: Clopidogrel<br>* 75mg tablet administered orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the effect of multiple doses (2 doses) of ISIS 681257 40 mg subcutaneous injections on the PK of multiple oral doses of clopidogrel in healthy adult subjects | The plasma concentrations of Clopidogrel and ISIS 681257 will be measured at each individual time point. | 55 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the safety of multiple doses (2 doses) of ISIS 681257 40 mg subcutaneous injections when co-administered with multiple oral doses of clopidogrel in healthy adult subjects | Safety will be assessed by summarizing the reported adverse events | 55 days | 
| Evaluate the effect of multiple doses (2 doses) of ISIS 681257 40 mg subcutaneous injections on the pharmacodynamics (antiplatelet activity) of multiple doses of clopidogrel in healthy adult subjects | P2Y12 reaction units (PRUs) will be measured at each individual time point. | 55 days |