Pharmacokinetic and Pharmacodynamic Assessment of a Novel, Pharmaceutical Lipid-Aspirin Complex

Study Overview
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Brief Summary
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Prospective, Randomized, Crossover, Bioequivalence study

Detailed Description
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Active-control crossover study randomizing 32 healthy volunteers to receive one of two dose levels, 325 mg or 650 mg, of either PL-ASA or immediate release aspirin within a two week washout period between treatments. The primary objectives are to assess PK and PD bioequivalence and safety over a twenty four hour period for PL-ASA and immediate release aspirin at 325 mg and 650 mg dose strengths.

Official Title
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Pharmacokinetic and Pharmacodynamic Assessment of a Novel, Pharmaceutical Lipid-Aspirin Complex

Conditions
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Bioequivalence

Intervention / Treatment
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* Drug: Aspirin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: If female and of childbearing potential, subject has a negative pregnancy test and is not nursing. If female and of childbearing potential, subject is using adequate birth control for the duration of the study. Subject is able to understand and comply with study procedures. Subject is a non-smoker. Subject consumes no more than 1 alcoholic drink per day. Subject agrees to refrain from alcohol consumption for 48 hours prior to each drug administration and 48 hours after each drug administration. Subject is able and willing to provide written informed consent prior to any study procedures being performed. Exclusion Criteria: Subject has abnormal screening/baseline laboratory parameters deemed to be clinically significant by the Investigator. Subject has taken any prescription medications other than hormone replacement therapy or thyroid replacement hormones within 3 days prior to drug administration. Subject has taken any of the following medications within 2 weeks prior to study entry: NSAIDs or other medications for pain, including aspirin or aspirin containing products and acetaminophen (see Appendix B of protocol in Appendix 16.1.1) Proton pump inhibitors, including Prilosec®, Prevacid®, Aciphex®, Protonix®, or Nexium® H-2 blockers, including Tagamet®, Zantac®, Axid®, or Pepcid® Any antiplatelet agent, including Plavix®, Ticlid®, Pletal®, ReoPro®, Integrilin®, Aggrastat®, or Persantine® Any anti-coagulant, including Coumadin®, Acenocoumarol, Phenprocoumon, Phenindione, Heparin, Exanta®, Argatroban, Lepirudin, Hirudin or Bivalirudin Subject has used an investigational agent within the past 30 days. Subject has hypersensitivity or contraindications to aspirin, ibuprofen, or other NSAID. Subject has sensitivity to lecithin. Subject has a history of gastrointestinal problems including ulcers, frequent indigestion, or heartburn. Subject has a history of stroke, myocardial infarction, or congestive heart failure. Subject has a history of asthma, other bronchospastic activity, nasal polyps, or angioedema other than resolved childhood asthma. Subject has a history of kidney or liver disease. Subject has a history of thrombocytopenia, neutropenia, or bleeding disorder. Subject has a history of coronary arterial bypass. Subject has a history of non-trauma related hemorrhage. Subject has a history of chronic hypertension. Subject is currently enrolled in another investigational trial. Subject's platelets are unresponsive to arachidonic acid

Ages Eligible for Study
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Minimum Age: 21 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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: 32 subjects to be randomized to treatment with either immediate release aspirin or PL-ASA at one of two doses (325 mg or 650 mg) administered orally. After completion of the first treatment and a minimum of a two week washout period(14-17 days) subjects are to cross over and receive treatment with the alternative compound at the same dose level.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PL-ASA 325 mg<br>Novel aspirin formulation being tested | Drug: Aspirin<br>* Aspirin - lipid complex<br>|
| Active Comparator: IR 325 mg<br>Immediate release aspirin | Drug: Aspirin<br>* Aspirin - lipid complex<br>|
| Experimental: PL-ASA-650<br>Novel aspirin formulation being tested | Drug: Aspirin<br>* Aspirin - lipid complex<br>|
| Active Comparator: IR 650<br>Immediate release aspirin | Drug: Aspirin<br>* Aspirin - lipid complex<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bioequivalence of PL-ASA and Immediate Release Aspirin AUC0-T | Assess for bioequivalence at 325 mg and 650 mg dose levels AUC0-T of the metabolite salicylic acid | twenty four hours | 
| Bioequivalence of PL-ASA and Immediate Release Aspirin AUC0-∞ | Assess for bioequivalence at 325 mg and 650 mg dose levels AUC0-∞ of the metabolite salicylic acid | 24 hours | 
| Bioequivalence of PL-ASA and Immediate Release Aspirin CMAX | Assess for bioequivalence at 325 mg and 650 mg dose levels CMAX of the metabolite salicylic acid | 24 hours | 
| Bioequivalence of PL-ASA and Immediate Release Aspirin TMAX | Assess for bioequivalence at 325 mg and 650 mg dose levels TMAX of the metabolite salicylic acid | 24 hours | 
| Bioequivalence of PL-ASA and Immediate Release Aspirin AUC0-24 | Assess for bioequivalence at 325 mg and 650 mg dose levels AUC0-24 of the percent inhibition of serum Thromboxane B2 | 24 hours | 
| Bioequivalence of PL-ASA and Immediate Release Aspirin TMAX STB2 | Assess for bioequivalence at 325 mg and 650 mg dose levels TMAX of the percent inhibition of serum Thromboxane B2 | 24 hours |