TY - JOUR
T1 - Pharmacokinetic/pharmacodynamic assessment of a novel, pharmaceutical lipid–aspirin complex
T2 - results of a randomized, crossover, bioequivalence study
AU - Angiolillo, Dominick J.
AU - Bhatt, Deepak L.
AU - Lanza, Frank
AU - Cryer, Byron
AU - Dong, Jin fei
AU - Jeske, Walter
AU - Zimmerman, Ronald R.
AU - von Chong, Estela
AU - Prats, Jayne
AU - Deliargyris, Efthymios N.
AU - Marathi, Upendra
N1 - Publisher Copyright:
© 2019, The Author(s).
PY - 2019/11/1
Y1 - 2019/11/1
N2 - Aspirin (acetylsalicylic acid, ASA) can lead to gastrointestinal mucosal injury through disruption of its protective phospholipid bilayer. A liquid formulation of a novel pharmaceutical lipid–aspirin complex (PL-ASA) was designed to prevent this disruption. We sought to determine the pharmacokinetic (PK)/pharmacodynamic (PD) characteristics of PL-ASA compared with immediate release aspirin (IR-ASA). In this active-control crossover study, 32 healthy volunteers were randomized to receive 1 of 2 dose levels (a single dose of 325 mg or 650 mg) of either PL-ASA or IR-ASA. After a 2-week washout period between treatment assignments, subjects received a single dose of the alternative treatment, at the same dose level. The primary objectives of the study were to assess, for PL-ASA and IR-ASA at 325 mg and 650 mg dose levels, PK and PD bioequivalence, and safety, over a 24–h period after administration of both drugs. PK parameters were similar for PL-ASA and IR-ASA, and met FDA-criteria for bioequivalence. Regarding PD, both drugs also showed Cmin TxB2 values below 3.1 ng/mL (cut-off associated with decreased cardiovascular events) and > 99% inhibition of serum TxB2 (≥ 95% inhibition represents the cut-off for aspirin responders) along with similar results in several secondary PK/PD parameters. There were no serious adverse events or changes from baseline in vital signs or laboratory values in either of the 2 treatment groups. PL-ASA’s novel liquid formulation has similar PK and PD performance compared with IR-ASA, supporting functional and clinical equivalence. These data coupled with the improved gastric safety of PL-ASA suggest that this novel formulation may exhibit an improved benefit-risk profile, warranting evaluation in future trials. Clinical trial registration:http://www.clinicaltrials.gov. Unique Identifier: NCT04008979.
AB - Aspirin (acetylsalicylic acid, ASA) can lead to gastrointestinal mucosal injury through disruption of its protective phospholipid bilayer. A liquid formulation of a novel pharmaceutical lipid–aspirin complex (PL-ASA) was designed to prevent this disruption. We sought to determine the pharmacokinetic (PK)/pharmacodynamic (PD) characteristics of PL-ASA compared with immediate release aspirin (IR-ASA). In this active-control crossover study, 32 healthy volunteers were randomized to receive 1 of 2 dose levels (a single dose of 325 mg or 650 mg) of either PL-ASA or IR-ASA. After a 2-week washout period between treatment assignments, subjects received a single dose of the alternative treatment, at the same dose level. The primary objectives of the study were to assess, for PL-ASA and IR-ASA at 325 mg and 650 mg dose levels, PK and PD bioequivalence, and safety, over a 24–h period after administration of both drugs. PK parameters were similar for PL-ASA and IR-ASA, and met FDA-criteria for bioequivalence. Regarding PD, both drugs also showed Cmin TxB2 values below 3.1 ng/mL (cut-off associated with decreased cardiovascular events) and > 99% inhibition of serum TxB2 (≥ 95% inhibition represents the cut-off for aspirin responders) along with similar results in several secondary PK/PD parameters. There were no serious adverse events or changes from baseline in vital signs or laboratory values in either of the 2 treatment groups. PL-ASA’s novel liquid formulation has similar PK and PD performance compared with IR-ASA, supporting functional and clinical equivalence. These data coupled with the improved gastric safety of PL-ASA suggest that this novel formulation may exhibit an improved benefit-risk profile, warranting evaluation in future trials. Clinical trial registration:http://www.clinicaltrials.gov. Unique Identifier: NCT04008979.
KW - Aspirin
KW - Bioequivalence
KW - Pharmacodynamic
KW - Pharmacokinetic
KW - Platelet
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UR - http://www.scopus.com/inward/citedby.url?scp=85070946243&partnerID=8YFLogxK
U2 - 10.1007/s11239-019-01933-7
DO - 10.1007/s11239-019-01933-7
M3 - Article
C2 - 31420787
AN - SCOPUS:85070946243
SN - 0929-5305
VL - 48
SP - 554
EP - 562
JO - Journal of Thrombosis and Thrombolysis
JF - Journal of Thrombosis and Thrombolysis
IS - 4
ER -