Muvalaplin, an Oral Small Molecule Inhibitor of Lipoprotein(a) Formation: A Randomized Clinical Trial
IMPORTANCE: Lipoprotein(a) (Lp[a]) is associated with atherosclerotic disease and aortic stenosis. Lp(a) forms by bonding between apolipoprotein(a) (apo[a]) and apo B100. Muvalaplin is an orally administered small molecule that inhibits Lp(a) formation by blocking the apo(a)-apo B100 interaction whi...
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| Published in | JAMA : the journal of the American Medical Association Vol. 330; no. 11; pp. 1042 - 1053 |
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| Main Authors | , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
American Medical Association
19.09.2023
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| Abstract | IMPORTANCE: Lipoprotein(a) (Lp[a]) is associated with atherosclerotic disease and aortic stenosis. Lp(a) forms by bonding between apolipoprotein(a) (apo[a]) and apo B100. Muvalaplin is an orally administered small molecule that inhibits Lp(a) formation by blocking the apo(a)-apo B100 interaction while avoiding interaction with a homologous protein, plasminogen. OBJECTIVE: To determine the safety, tolerability, pharmacokinetics, and pharmacodynamic effects of muvalaplin. DESIGN, SETTING, AND PARTICIPANTS: This phase 1 randomized, double-blind, parallel-design study enrolled 114 participants (55 assigned to a single-ascending dose; 59 assigned to a multiple-ascending dose group) at 1 site in the Netherlands. INTERVENTIONS: The single ascending dose treatment evaluated the effect of a single dose of muvalaplin ranging from 1 mg to 800 mg or placebo taken by healthy participants with any Lp(a) level. The multiple ascending dose treatment evaluated the effect of taking daily doses of muvalaplin (30 mg to 800 mg) or placebo for 14 days in patients with Lp(a) levels of 30 mg/dL or higher. MAIN OUTCOMES AND MEASURES: Outcomes included safety, tolerability, pharmacokinetics, and exploratory pharmacodynamic biomarkers. RESULTS: Among 114 randomized (55 in the single ascending dose group: mean [SD] age, 29 [10] years, 35 females [64%], 2 American Indian or Alaska Native [4%], 50 White [91%], 3 multiracial [5%]; 59 in the multiple ascending dose group: mean [SD] age 32 [15] years; 34 females [58%]; 3 American Indian or Alaska Native [5%], 6 Black [10%], 47 White [80%], 3 multiracial [5%]), 105 completed the trial. Muvalaplin was not associated with tolerability concerns or clinically significant adverse effects. Oral doses of 30 mg to 800 mg for 14 days resulted in increasing muvalaplin plasma concentrations and half-life ranging from 70 to 414 hours. Muvalaplin lowered Lp(a) plasma levels within 24 hours after the first dose, with further Lp(a) reduction on repeated dosing. Maximum placebo-adjusted Lp(a) reduction was 63% to 65%, resulting in Lp(a) plasma levels less than 50 mg/dL in 93% of participants, with similar effects at daily doses of 100 mg or more. No clinically significant changes in plasminogen levels or activity were observed. CONCLUSION: Muvalaplin, a selective small molecule inhibitor of Lp(a) formation, was not associated with tolerability concerns and lowered Lp(a) levels up to 65% following daily administration for 14 days. Longer and larger trials will be required to further evaluate safety, tolerability, and effect of muvalaplin on Lp(a) levels and cardiovascular outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04472676 |
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| AbstractList | Lipoprotein(a) (Lp[a]) is associated with atherosclerotic disease and aortic stenosis. Lp(a) forms by bonding between apolipoprotein(a) (apo[a]) and apo B100. Muvalaplin is an orally administered small molecule that inhibits Lp(a) formation by blocking the apo(a)-apo B100 interaction while avoiding interaction with a homologous protein, plasminogen.ImportanceLipoprotein(a) (Lp[a]) is associated with atherosclerotic disease and aortic stenosis. Lp(a) forms by bonding between apolipoprotein(a) (apo[a]) and apo B100. Muvalaplin is an orally administered small molecule that inhibits Lp(a) formation by blocking the apo(a)-apo B100 interaction while avoiding interaction with a homologous protein, plasminogen.To determine the safety, tolerability, pharmacokinetics, and pharmacodynamic effects of muvalaplin.ObjectiveTo determine the safety, tolerability, pharmacokinetics, and pharmacodynamic effects of muvalaplin.This phase 1 randomized, double-blind, parallel-design study enrolled 114 participants (55 assigned to a single-ascending dose; 59 assigned to a multiple-ascending dose group) at 1 site in the Netherlands.Design, Setting, and ParticipantsThis phase 1 randomized, double-blind, parallel-design study enrolled 114 participants (55 assigned to a single-ascending dose; 59 assigned to a multiple-ascending dose group) at 1 site in the Netherlands.The single ascending dose treatment evaluated the effect of a single dose of muvalaplin ranging from 1 mg to 800 mg or placebo taken by healthy participants with any Lp(a) level. The multiple ascending dose treatment evaluated the effect of taking daily doses of muvalaplin (30 mg to 800 mg) or placebo for 14 days in patients with Lp(a) levels of 30 mg/dL or higher.InterventionsThe single ascending dose treatment evaluated the effect of a single dose of muvalaplin ranging from 1 mg to 800 mg or placebo taken by healthy participants with any Lp(a) level. The multiple ascending dose treatment evaluated the effect of taking daily doses of muvalaplin (30 mg to 800 mg) or placebo for 14 days in patients with Lp(a) levels of 30 mg/dL or higher.Outcomes included safety, tolerability, pharmacokinetics, and exploratory pharmacodynamic biomarkers.Main Outcomes and MeasuresOutcomes included safety, tolerability, pharmacokinetics, and exploratory pharmacodynamic biomarkers.Among 114 randomized (55 in the single ascending dose group: mean [SD] age, 29 [10] years, 35 females [64%], 2 American Indian or Alaska Native [4%], 50 White [91%], 3 multiracial [5%]; 59 in the multiple ascending dose group: mean [SD] age 32 [15] years; 34 females [58%]; 3 American Indian or Alaska Native [5%], 6 Black [10%], 47 White [80%], 3 multiracial [5%]), 105 completed the trial. Muvalaplin was not associated with tolerability concerns or clinically significant adverse effects. Oral doses of 30 mg to 800 mg for 14 days resulted in increasing muvalaplin plasma concentrations and half-life ranging from 70 to 414 hours. Muvalaplin lowered Lp(a) plasma levels within 24 hours after the first dose, with further Lp(a) reduction on repeated dosing. Maximum placebo-adjusted Lp(a) reduction was 63% to 65%, resulting in Lp(a) plasma levels less than 50 mg/dL in 93% of participants, with similar effects at daily doses of 100 mg or more. No clinically significant changes in plasminogen levels or activity were observed.ResultsAmong 114 randomized (55 in the single ascending dose group: mean [SD] age, 29 [10] years, 35 females [64%], 2 American Indian or Alaska Native [4%], 50 White [91%], 3 multiracial [5%]; 59 in the multiple ascending dose group: mean [SD] age 32 [15] years; 34 females [58%]; 3 American Indian or Alaska Native [5%], 6 Black [10%], 47 White [80%], 3 multiracial [5%]), 105 completed the trial. Muvalaplin was not associated with tolerability concerns or clinically significant adverse effects. Oral doses of 30 mg to 800 mg for 14 days resulted in increasing muvalaplin plasma concentrations and half-life ranging from 70 to 414 hours. Muvalaplin lowered Lp(a) plasma levels within 24 hours after the first dose, with further Lp(a) reduction on repeated dosing. Maximum placebo-adjusted Lp(a) reduction was 63% to 65%, resulting in Lp(a) plasma levels less than 50 mg/dL in 93% of participants, with similar effects at daily doses of 100 mg or more. No clinically significant changes in plasminogen levels or activity were observed.Muvalaplin, a selective small molecule inhibitor of Lp(a) formation, was not associated with tolerability concerns and lowered Lp(a) levels up to 65% following daily administration for 14 days. Longer and larger trials will be required to further evaluate safety, tolerability, and effect of muvalaplin on Lp(a) levels and cardiovascular outcomes.ConclusionMuvalaplin, a selective small molecule inhibitor of Lp(a) formation, was not associated with tolerability concerns and lowered Lp(a) levels up to 65% following daily administration for 14 days. Longer and larger trials will be required to further evaluate safety, tolerability, and effect of muvalaplin on Lp(a) levels and cardiovascular outcomes.ClinicalTrials.gov Identifier: NCT04472676.Trial RegistrationClinicalTrials.gov Identifier: NCT04472676. IMPORTANCE: Lipoprotein(a) (Lp[a]) is associated with atherosclerotic disease and aortic stenosis. Lp(a) forms by bonding between apolipoprotein(a) (apo[a]) and apo B100. Muvalaplin is an orally administered small molecule that inhibits Lp(a) formation by blocking the apo(a)-apo B100 interaction while avoiding interaction with a homologous protein, plasminogen. OBJECTIVE: To determine the safety, tolerability, pharmacokinetics, and pharmacodynamic effects of muvalaplin. DESIGN, SETTING, AND PARTICIPANTS: This phase 1 randomized, double-blind, parallel-design study enrolled 114 participants (55 assigned to a single-ascending dose; 59 assigned to a multiple-ascending dose group) at 1 site in the Netherlands. INTERVENTIONS: The single ascending dose treatment evaluated the effect of a single dose of muvalaplin ranging from 1 mg to 800 mg or placebo taken by healthy participants with any Lp(a) level. The multiple ascending dose treatment evaluated the effect of taking daily doses of muvalaplin (30 mg to 800 mg) or placebo for 14 days in patients with Lp(a) levels of 30 mg/dL or higher. MAIN OUTCOMES AND MEASURES: Outcomes included safety, tolerability, pharmacokinetics, and exploratory pharmacodynamic biomarkers. RESULTS: Among 114 randomized (55 in the single ascending dose group: mean [SD] age, 29 [10] years, 35 females [64%], 2 American Indian or Alaska Native [4%], 50 White [91%], 3 multiracial [5%]; 59 in the multiple ascending dose group: mean [SD] age 32 [15] years; 34 females [58%]; 3 American Indian or Alaska Native [5%], 6 Black [10%], 47 White [80%], 3 multiracial [5%]), 105 completed the trial. Muvalaplin was not associated with tolerability concerns or clinically significant adverse effects. Oral doses of 30 mg to 800 mg for 14 days resulted in increasing muvalaplin plasma concentrations and half-life ranging from 70 to 414 hours. Muvalaplin lowered Lp(a) plasma levels within 24 hours after the first dose, with further Lp(a) reduction on repeated dosing. Maximum placebo-adjusted Lp(a) reduction was 63% to 65%, resulting in Lp(a) plasma levels less than 50 mg/dL in 93% of participants, with similar effects at daily doses of 100 mg or more. No clinically significant changes in plasminogen levels or activity were observed. CONCLUSION: Muvalaplin, a selective small molecule inhibitor of Lp(a) formation, was not associated with tolerability concerns and lowered Lp(a) levels up to 65% following daily administration for 14 days. Longer and larger trials will be required to further evaluate safety, tolerability, and effect of muvalaplin on Lp(a) levels and cardiovascular outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04472676 Lipoprotein(a) (Lp[a]) is associated with atherosclerotic disease and aortic stenosis. Lp(a) forms by bonding between apolipoprotein(a) (apo[a]) and apo B100. Muvalaplin is an orally administered small molecule that inhibits Lp(a) formation by blocking the apo(a)-apo B100 interaction while avoiding interaction with a homologous protein, plasminogen. To determine the safety, tolerability, pharmacokinetics, and pharmacodynamic effects of muvalaplin. This phase 1 randomized, double-blind, parallel-design study enrolled 114 participants (55 assigned to a single-ascending dose; 59 assigned to a multiple-ascending dose group) at 1 site in the Netherlands. The single ascending dose treatment evaluated the effect of a single dose of muvalaplin ranging from 1 mg to 800 mg or placebo taken by healthy participants with any Lp(a) level. The multiple ascending dose treatment evaluated the effect of taking daily doses of muvalaplin (30 mg to 800 mg) or placebo for 14 days in patients with Lp(a) levels of 30 mg/dL or higher. Outcomes included safety, tolerability, pharmacokinetics, and exploratory pharmacodynamic biomarkers. Among 114 randomized (55 in the single ascending dose group: mean [SD] age, 29 [10] years, 35 females [64%], 2 American Indian or Alaska Native [4%], 50 White [91%], 3 multiracial [5%]; 59 in the multiple ascending dose group: mean [SD] age 32 [15] years; 34 females [58%]; 3 American Indian or Alaska Native [5%], 6 Black [10%], 47 White [80%], 3 multiracial [5%]), 105 completed the trial. Muvalaplin was not associated with tolerability concerns or clinically significant adverse effects. Oral doses of 30 mg to 800 mg for 14 days resulted in increasing muvalaplin plasma concentrations and half-life ranging from 70 to 414 hours. Muvalaplin lowered Lp(a) plasma levels within 24 hours after the first dose, with further Lp(a) reduction on repeated dosing. Maximum placebo-adjusted Lp(a) reduction was 63% to 65%, resulting in Lp(a) plasma levels less than 50 mg/dL in 93% of participants, with similar effects at daily doses of 100 mg or more. No clinically significant changes in plasminogen levels or activity were observed. Muvalaplin, a selective small molecule inhibitor of Lp(a) formation, was not associated with tolerability concerns and lowered Lp(a) levels up to 65% following daily administration for 14 days. Longer and larger trials will be required to further evaluate safety, tolerability, and effect of muvalaplin on Lp(a) levels and cardiovascular outcomes. ClinicalTrials.gov Identifier: NCT04472676. This phase 1 randomized clinical trial evaluates the safety, tolerability, pharmacokinetics, and exploratory pharmacodynamic biomarker effects of muvalaplin in humans. Importance Lipoprotein(a) (Lp[a]) is associated with atherosclerotic disease and aortic stenosis. Lp(a) forms by bonding between apolipoprotein(a) (apo[a]) and apo B100. Muvalaplin is an orally administered small molecule that inhibits Lp(a) formation by blocking the apo(a)-apo B100 interaction while avoiding interaction with a homologous protein, plasminogen. Objective To determine the safety, tolerability, pharmacokinetics, and pharmacodynamic effects of muvalaplin. Design, Setting, and Participants This phase 1 randomized, double-blind, parallel-design study enrolled 114 participants (55 assigned to a single-ascending dose; 59 assigned to a multiple-ascending dose group) at 1 site in the Netherlands. Interventions The single ascending dose treatment evaluated the effect of a single dose of muvalaplin ranging from 1 mg to 800 mg or placebo taken by healthy participants with any Lp(a) level. The multiple ascending dose treatment evaluated the effect of taking daily doses of muvalaplin (30 mg to 800 mg) or placebo for 14 days in patients with Lp(a) levels of 30 mg/dL or higher. Main Outcomes and Measures Outcomes included safety, tolerability, pharmacokinetics, and exploratory pharmacodynamic biomarkers. Results Among 114 randomized (55 in the single ascending dose group: mean [SD] age, 29 [10] years, 35 females [64%], 2 American Indian or Alaska Native [4%], 50 White [91%], 3 multiracial [5%]; 59 in the multiple ascending dose group: mean [SD] age 32 [15] years; 34 females [58%]; 3 American Indian or Alaska Native [5%], 6 Black [10%], 47 White [80%], 3 multiracial [5%]), 105 completed the trial. Muvalaplin was not associated with tolerability concerns or clinically significant adverse effects. Oral doses of 30 mg to 800 mg for 14 days resulted in increasing muvalaplin plasma concentrations and half-life ranging from 70 to 414 hours. Muvalaplin lowered Lp(a) plasma levels within 24 hours after the first dose, with further Lp(a) reduction on repeated dosing. Maximum placebo-adjusted Lp(a) reduction was 63% to 65%, resulting in Lp(a) plasma levels less than 50 mg/dL in 93% of participants, with similar effects at daily doses of 100 mg or more. No clinically significant changes in plasminogen levels or activity were observed. Conclusion Muvalaplin, a selective small molecule inhibitor of Lp(a) formation, was not associated with tolerability concerns and lowered Lp(a) levels up to 65% following daily administration for 14 days. Longer and larger trials will be required to further evaluate safety, tolerability, and effect of muvalaplin on Lp(a) levels and cardiovascular outcomes. |
| Author | Linnebjerg, Helle Urva, Shweta Ruotolo, Giacomo Fleming, Cynthia Michael, Laura F Suico, Jeffrey Nicholls, Stephen J Nissen, Steven E Turner, P. Kellie Berg, Paul H |
| AuthorAffiliation | 2 Cleveland Clinic Coordinating Center for Clinical Research, Cleveland Clinic, Cleveland, Ohio 3 Eli Lilly and Company, Indianapolis, Indiana 1 Victorian Heart Institute, Monash University, Clayton, Victoria, Australia |
| AuthorAffiliation_xml | – name: 3 Eli Lilly and Company, Indianapolis, Indiana – name: 1 Victorian Heart Institute, Monash University, Clayton, Victoria, Australia – name: 2 Cleveland Clinic Coordinating Center for Clinical Research, Cleveland Clinic, Cleveland, Ohio |
| Author_xml | – sequence: 1 givenname: Stephen J surname: Nicholls fullname: Nicholls, Stephen J – sequence: 2 givenname: Steven E surname: Nissen fullname: Nissen, Steven E – sequence: 3 givenname: Cynthia surname: Fleming fullname: Fleming, Cynthia – sequence: 4 givenname: Shweta surname: Urva fullname: Urva, Shweta – sequence: 5 givenname: Jeffrey surname: Suico fullname: Suico, Jeffrey – sequence: 6 givenname: Paul H surname: Berg fullname: Berg, Paul H – sequence: 7 givenname: Helle surname: Linnebjerg fullname: Linnebjerg, Helle – sequence: 8 givenname: Giacomo surname: Ruotolo fullname: Ruotolo, Giacomo – sequence: 9 givenname: P. Kellie surname: Turner fullname: Turner, P. Kellie – sequence: 10 givenname: Laura F surname: Michael fullname: Michael, Laura F |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/37638695$$D View this record in MEDLINE/PubMed |
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| Copyright | Copyright American Medical Association Sep 19, 2023 Copyright 2023 American Medical Association. All Rights Reserved. |
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| References | Nissen (jpc230005r9) 2022; 327 O’Donoghue (jpc230005r8) 2022; 387 Kamstrup (jpc230005r3) 2009; 301 Tsimikas (jpc230005r7) 2020; 382 McLean (jpc230005r11) 1987; 330 Ogorelkova (jpc230005r12) 1999; 8 Ogorelkova (jpc230005r13) 2001; 10 Hanssen (jpc230005r6) 2017; 24 Kayikcioglu (jpc230005r19) 2021; 23 Reyes-Soffer (jpc230005r22) 2022; 42 Berg (jpc230005r10) 1963; 59 Kronenberg (jpc230005r16) 2019; 288 Erqou (jpc230005r2) 2009; 302 Patel (jpc230005r14) 2021; 41 Clarke (jpc230005r4) 2009; 361 Kronenberg (jpc230005r1) 2022; 43 Madsen (jpc230005r15) 2020; 40 O’Donoghue (jpc230005r20) 2019; 139 Roeseler (jpc230005r18) 2016; 36 Mach (jpc230005r17) 2020; 41 Bittner (jpc230005r21) 2020; 75 Burgess (jpc230005r5) 2018; 3 |
| References_xml | – volume: 36 start-page: 2019 issue: 9 year: 2016 ident: jpc230005r18 article-title: Lipoprotein apheresis for lipoprotein(a)-associated cardiovascular disease: prospective 5 years of follow-up and apolipoprotein(a) characterization. publication-title: Arterioscler Thromb Vasc Biol doi: 10.1161/ATVBAHA.116.307983 – volume: 139 start-page: 1483 issue: 12 year: 2019 ident: jpc230005r20 article-title: Lipoprotein(a), PCSK9 inhibition, and cardiovascular risk. publication-title: Circulation doi: 10.1161/CIRCULATIONAHA.118.037184 – volume: 327 start-page: 1679 issue: 17 year: 2022 ident: jpc230005r9 article-title: Single ascending dose study of a short interfering RNA targeting lipoprotein(a) production in individuals with elevated plasma lipoprotein(a) levels. publication-title: JAMA doi: 10.1001/jama.2022.5050 – volume: 24 start-page: 957 issue: 10 year: 2017 ident: jpc230005r6 article-title: Lipoprotein(a) management: pharmacological and apheretic treatment. publication-title: Curr Med Chem doi: 10.2174/0929867324666170112110928 – volume: 361 start-page: 2518 issue: 26 year: 2009 ident: jpc230005r4 article-title: Genetic variants associated with Lp(a) lipoprotein level and coronary disease. publication-title: N Engl J Med doi: 10.1056/NEJMoa0902604 – volume: 302 start-page: 412 issue: 4 year: 2009 ident: jpc230005r2 article-title: Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality. publication-title: JAMA doi: 10.1001/jama.2009.1063 – volume: 75 start-page: 133 issue: 2 year: 2020 ident: jpc230005r21 article-title: Effect of alirocumab on lipoprotein(a) and cardiovascular risk after acute coronary syndrome. publication-title: J Am Coll Cardiol doi: 10.1016/j.jacc.2019.10.057 – volume: 3 start-page: 619 issue: 7 year: 2018 ident: jpc230005r5 article-title: Association of LPA variants with risk of coronary disease and the implications for lipoprotein(a)-lowering therapies: a MENDELIAN randomization analysis. publication-title: JAMA Cardiol doi: 10.1001/jamacardio.2018.1470 – volume: 41 start-page: 465 issue: 1 year: 2021 ident: jpc230005r14 article-title: Lp(a) (lipoprotein[a]) concentrations and incident atherosclerotic cardiovascular disease: new insights from a large national biobank. publication-title: Arterioscler Thromb Vasc Biol doi: 10.1161/ATVBAHA.120.315291 – volume: 43 start-page: 3925 issue: 39 year: 2022 ident: jpc230005r1 article-title: Lipoprotein(a) in atherosclerotic cardiovascular disease and aortic stenosis: a European Atherosclerosis Society consensus statement. publication-title: Eur Heart J doi: 10.1093/eurheartj/ehac361 – volume: 382 start-page: 244 issue: 3 year: 2020 ident: jpc230005r7 article-title: Lipoprotein(a) reduction in persons with cardiovascular disease. publication-title: N Engl J Med doi: 10.1056/NEJMoa1905239 – volume: 288 start-page: 163 year: 2019 ident: jpc230005r16 article-title: Therapeutic lowering of lipoprotein(a): how much is enough? publication-title: Atherosclerosis doi: 10.1016/j.atherosclerosis.2019.07.003 – volume: 23 start-page: 15 issue: 4 year: 2021 ident: jpc230005r19 article-title: LDL Apheresis and Lp (a) apheresis: a clinician’s perspective. publication-title: Curr Atheroscler Rep doi: 10.1007/s11883-021-00911-w – volume: 330 start-page: 132 issue: 6144 year: 1987 ident: jpc230005r11 article-title: cDNA sequence of human apolipoprotein(a) is homologous to plasminogen. publication-title: Nature doi: 10.1038/330132a0 – volume: 301 start-page: 2331 issue: 22 year: 2009 ident: jpc230005r3 article-title: Genetically elevated lipoprotein(a) and increased risk of myocardial infarction. publication-title: JAMA doi: 10.1001/jama.2009.801 – volume: 41 start-page: 111 issue: 1 year: 2020 ident: jpc230005r17 article-title: 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. publication-title: Eur Heart J doi: 10.1093/eurheartj/ehz455 – volume: 387 start-page: 1855 issue: 20 year: 2022 ident: jpc230005r8 article-title: Small interfering RNA to reduce lipoprotein(a) in cardiovascular disease. publication-title: N Engl J Med doi: 10.1056/NEJMoa2211023 – volume: 10 start-page: 815 issue: 8 year: 2001 ident: jpc230005r13 article-title: Single nucleotide polymorphisms in exons of the apo(a) kringles IV types 6 to 10 domain affect Lp(a) plasma concentrations and have different patterns in Africans and Caucasians. publication-title: Hum Mol Genet doi: 10.1093/hmg/10.8.815 – volume: 40 start-page: 255 issue: 1 year: 2020 ident: jpc230005r15 article-title: Lipoprotein(a)-lowering by 50 mg/dL (105 nmol/L) may be needed to reduce cardiovascular disease 20% in secondary prevention: a population-based study. publication-title: Arterioscler Thromb Vasc Biol doi: 10.1161/ATVBAHA.119.312951 – volume: 59 start-page: 369 year: 1963 ident: jpc230005r10 article-title: A new serum type system in man—the Lp(a) system. publication-title: Acta Pathol Microbiol Scand doi: 10.1111/j.1699-0463.1963.tb01808.x – volume: 8 start-page: 2087 issue: 11 year: 1999 ident: jpc230005r12 article-title: Molecular basis of congenital Lp(a) deficiency: a frequent apo(a) ‘null’ mutation in Caucasians. publication-title: Hum Mol Genet doi: 10.1093/hmg/8.11.2087 – volume: 42 start-page: e48 issue: 1 year: 2022 ident: jpc230005r22 article-title: Lipoprotein(a): a genetically determined, causal, and prevalent risk factor for atherosclerotic cardiovascular disease: a scientific statement from the American Heart Association. publication-title: Arterioscler Thromb Vasc Biol doi: 10.1161/ATV.0000000000000147 |
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| Snippet | IMPORTANCE: Lipoprotein(a) (Lp[a]) is associated with atherosclerotic disease and aortic stenosis. Lp(a) forms by bonding between apolipoprotein(a) (apo[a])... Lipoprotein(a) (Lp[a]) is associated with atherosclerotic disease and aortic stenosis. Lp(a) forms by bonding between apolipoprotein(a) (apo[a]) and apo B100.... Importance Lipoprotein(a) (Lp[a]) is associated with atherosclerotic disease and aortic stenosis. Lp(a) forms by bonding between apolipoprotein(a) (apo[a]) and... This phase 1 randomized clinical trial evaluates the safety, tolerability, pharmacokinetics, and exploratory pharmacodynamic biomarker effects of muvalaplin in... |
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| SubjectTerms | Administration, Oral Adolescent Adult American Indian or Alaska Native Aorta Aortic stenosis Apolipoproteins Apoprotein(a) - antagonists & inhibitors Arteriosclerosis Atherosclerosis Biomarkers Black or African American Cardiovascular Agents - administration & dosage Cardiovascular Agents - adverse effects Cardiovascular Agents - therapeutic use Clinical significance Clinical trials Dosage Dose-Response Relationship, Drug Double-Blind Method Double-blind studies Female Females Health services Humans Hypolipidemic Agents - administration & dosage Hypolipidemic Agents - adverse effects Hypolipidemic Agents - therapeutic use Inhibitors Lipoprotein(a) - antagonists & inhibitors Male Middle Aged Online First Oral administration Pharmacodynamics Pharmacokinetics Placebos Plasma levels Plasminogen Preliminary Communication Racial Groups Reduction Safety White Young Adult |
| Title | Muvalaplin, an Oral Small Molecule Inhibitor of Lipoprotein(a) Formation: A Randomized Clinical Trial |
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