Pharmacodynamic Profile of PL-ASA, a Novel Phospholipid-Aspirin Complex Liquid Formulation, - PowerPoint Presentation

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Pharmacodynamic Profile of PL-ASA, a Novel Phospholipid-Aspirin Complex Liquid Formulation, Compared to Enteric-coated Aspirin at an 81 mg Dose ─ Results from a Prospective, Randomized, Crossover Study

Franchi F, Schneider DJ, Prats J, Fan W,

Rollini

F, Been L,

Taatjes

-Sommer HS,

Deliargyris

EN,

Angiolillo

DJ

TCT 2021

Background

Immediate release (IR) aspirin (IR-ASA) is associated with risk of mucosal damage in the upper gastrointestinal (GI) tract.

Enteric coated aspirin (EC-ASA) was designed to reduce GI injury by bypassing the stomach and releasing ASA in the duodenum and is today the standard of care in secondary prevention. However, evidence shows that EC-ASA results in greater variability in absorption and antiplatelet effect than IR-ASA.

PL-ASA (VAZALORE, PLx Pharma Inc.), a novel FDA-approved, liquid-filled phospholipid-ASA capsule, is an IR formulation, designed to release aspirin in the duodenum, thus limiting GI injury, while still providing fast and complete drug absorption and potent and reliable COX-1 inhibition. Previous studies have compared the 325-mg dose of PL-ASA to IR-ASA and EC- ASA; this study is the first to investigate the pharmacokinetics (PK) of the 81-mg dose of PL-ASA. We also sought to assess the early pharmacodynamic (PD) effects of PL-ASA compared to EC-ASA

Franchi F et al TCT 2021

Methods

This is a randomized, open-label, crossover study assessing PK and PD after a single 81-mg dose of PL-ASA vs. EC-ASA under fasting conditions in 36 subjects between 18 and 75 years of age.

Subjects were randomly assigned 1:1 to either PL-ASA followed by EC-ASA or EC-ASA followed by PL-ASA with a 14-day washout

period between the two study drugs. PK parameters for acetylsalicylic acid and salicylic acid were obtained. PD assessments included the comparison between PL-ASA and EC-ASA for platelet aggregation following arachidonic acid (AA) and collagen stimuli, and measurement of thromboxane B2 (TxB2)

Franchi F et al TCT 2021

Demographic Results

36 subjects were randomized and completed the study

mean age: 48.8 years (range: 22 - 69)

females: 26 (72.2%) race: 26 white, 6 black mean BMI: 34.5 kg/m2

Franchi F et al TCT 2021

Pharmacokinetic Profile

Plasma concentrations over time (mean, n=36)

Acetylsalicylic Acid

Acetylsalicylic Acid

Salicylic Acid

Franchi F et al TCT 2021

PL-ASA Provides Faster Absorption and More Complete Bioavailability vs. EC Aspirin

PK Parameters

EC ASA

PL-ASA

P-

value

a

Acetylsalicylic acid

(N=23)

(N=34)

C

max

(ng/mL)

367.86

720.10

<0.0001

AUC

0-t

(

hr*ng/mL)416.13600.730.001 Tmax (hr)4.00 (1.50, 6.63)1.01 (0.47, 3.03)<0.0001Salicylic acid (N=36)  (N=36)   Cmax (ng/mL)2940.934095.24<0.0001 AUC0-t (hr*ng/mL)13123.9614848.450.02 Tmax (hr)4.89 (2.00, 11.9)1.52 (0.55, 5.92)<0.0001

Cmax and AUC are presented as geometric least-square mean; Tmax is presented as median (minimum, maximum).a: All p-values were calculated by using mixed-effect, repeated measure ANOVA model with sequence, period, and treatment as fixed effects, and subject as random effect.

Cmax and AUC are presented as geometric least-square mean; Tmax is presented as median (minimum, maximum).a: All p-values were calculated by using mixed-effect, repeated measure ANOVA model with sequence, period, and treatment as fixed effects, and subject as random effect.

Franchi F et al TCT 2021

Pharmacodynamic Profile: LTA

Arachidonic Acid-Induced Light Transmission Aggregometry

(LTA) over Time (median, n=36)

Franchi F et al TCT 2021

PL-ASA Provides Faster and Stronger Platelet Inhibition with Lower Levels of AA-induced Platelet Aggregation vs. EC-ASA

Conclusions

Table: PK Parameters

EC ASA

PL-ASA

P-

value

a

Acetylsalicylic acid

(N=23)

(N=34)

C

max

(ng/mL)

367.86

720.10

<0.0001

AUC

0-t

(hr*ng/mL)416.13600.730.001 Tmax (hr)4.00 (1.50, 6.63)1.01 (0.47, 3.03)<0.0001Salicylic acid (N=36)  (N=36)   Cmax (ng/mL)2940.934095.24<0.0001 AUC0-t (hr*ng/mL)13123.9614848.450.02 Tmax (hr)4.89 (2.00, 11.9)1.52 (0.55, 5.92)<0.0001

Table: PK Parameters  EC ASA PL-ASAP-valuea

Acetylsalicylic acid(N=23) (N=34)

C

max

(ng/mL)

367.86

720.10

<0.0001

AUC

0-t

(

hr*ng/mL)416.13600.730.001 Tmax (hr)4.00 (1.50, 6.63)1.01 (0.47, 3.03)<0.0001Salicylic acid (N=36)  (N=36)   Cmax (ng/mL)2940.934095.24<0.0001 AUC0-t (hr*ng/mL)13123.9614848.450.02 Tmax (hr)4.89 (2.00, 11.9)1.52 (0.55, 5.92)<0.0001

Table: PK Parameters  EC ASA PL-ASAP-valueaAcetylsalicylic acid(N=23) (N=34) Cmax (ng/mL) 367.86720.10<0.0001 AUC0-t (hr*ng/mL)416.13600.730.001 Tmax (hr)4.00 (1.50, 6.63)1.01 (0.47, 3.03)<0.0001Salicylic acid (N=36)  (N=36)   Cmax (ng/mL)2940.934095.24<0.0001 AUC0-t (hr*ng/mL)13123.9614848.450.02 Tmax (hr)4.89 (2.00, 11.9)1.52 (0.55, 5.92)<0.0001

PK Profile: PL-ASA, a novel phospholipid-aspirin formulation in a liquid-filled capsule that has been shown to be bioequivalent to IR-ASA, results in faster and more complete absorption after a single 81 mg dose compared to EC-ASA.PD Profile: In arachidonic acid-induced platelet aggregation, as assessed by light transmission aggregometry, PL-ASA provides more potent and earlier inhibition of platelet aggregation compared to EC-ASA. Assessments of TxB2 (data not shown) were consistent with LTA results. The observations of the current study are consistent with previous findings from published comparative studies with the 325 mg dose.1,2 PL-ASA is a novel aspirin formulation that provides more predictable PK and PD effects compared with enteric-coated aspirin.

1Angiolillo et al, J Thromb Thrombolysis 2019;48:554–622Bhatt DL, Grosser T, Dong J et al JACC

Franchi F et al TCT 2021