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

Prospective, Randomized, Crossover, Bioequivalence study

Study Overview

• Status: Completed
• Conditions: Bioequivalence
• Intervention / Treatment: Drug: Aspirin

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: PLx Pharma
• Investigators: Study Director: Upendra Marathi, PhD, PLx Pharma

Publications and helpful links

General Publications

• Angiolillo DJ, Bhatt DL, Lanza F, Cryer B, Dong JF, Jeske W, Zimmerman RR, von Chong E, Prats J, Deliargyris EN, Marathi U. Pharmacokinetic/pharmacodynamic assessment of a novel, pharmaceutical lipid-aspirin complex: results of a randomized, crossover, bioequivalence study. J Thromb Thrombolysis. 2019 Nov;48(4):554-562. doi: 10.1007/s11239-019-01933-7.

Study record dates

Study Major Dates

• Study Start (Actual): February 11, 2008
• Primary Completion (Actual): June 10, 2008
• Study Completion (Actual): June 10, 2008

Study Registration Dates

• First Submitted: July 2, 2019
• First Submitted That Met QC Criteria: July 3, 2019
• First Posted (Actual): July 5, 2019

Study Record Updates

• Last Update Posted (Actual): July 5, 2019
• Last Update Submitted That Met QC Criteria: July 3, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Aspirin
• Other Study ID Numbers: 74,290

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No