Clinical Trial Protocol: Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Efficacy, and Safety Study Comparing EG-1962 to Standard of Care Oral Nimodipine in Adults with Aneurysmal Subarachnoid Hemorrhage [NEWTON-2 (Nimodipine Microparticles to Enhance Recovery While Reducing TOxicity After SubarachNoid Hemorrhage)]
Background Nimodipine is the only drug approved in the treatment of aneurysmal subarachnoid hemorrhage (aSAH) in many countries. EG-1962, a product developed using the Precisa™ platform, is an extended-release microparticle formulation of nimodipine that can be administered intraventricularly or int...
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| Veröffentlicht in: | Neurocritical care 2019-02, Vol.30 (1), p.88-97 |
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| creator | Hänggi, Daniel Etminan, Nima Mayer, Stephan A. Aldrich, E. Francois Diringer, Michael N. Schmutzhard, Erich Faleck, Herbert J. Ng, David Saville, Benjamin R. Macdonald, R. Loch |
| description | Background
Nimodipine is the only drug approved in the treatment of aneurysmal subarachnoid hemorrhage (aSAH) in many countries. EG-1962, a product developed using the Precisa™ platform, is an extended-release microparticle formulation of nimodipine that can be administered intraventricularly or intracisternally. It was developed to test the hypothesis that delivering higher concentrations of extended-release nimodipine directly to the cerebrospinal fluid would provide superior efficacy compared to systemic administration.
Results
A Phase 1/2a multicenter, controlled, randomized, open-label, dose-escalation study determined the maximum tolerated dose and supported the safety and tolerability of EG-1962 in patients with aSAH. EG-1962, 600 mg, was selected for a pivotal, Phase 3 multicenter, randomized, double-blind, placebo-controlled, parallel-group efficacy, and safety study comparing it to standard of care oral nimodipine in adults with aSAH. Key inclusion criteria are patients with a ruptured saccular aneurysm repaired by clipping or coiling, World Federation of Neurological Surgeons grade 2–4, and modified Fisher score of > 1. Patients must have an external ventricular drain as part of standard of care. Patients are randomized to receive intraventricular investigational product (EG-1962 or NaCl solution) and an oral placebo or oral nimodipine in the approved dose regimen (active control) within 48 h of aSAH. The primary objective is to determine the efficacy of EG-1962 compared to oral nimodipine.
Conclusions
The primary endpoint is the proportion of subjects with favorable outcome (6–8) on the Extended Glasgow Outcome Scale assessed 90 days after aSAH. The secondary endpoint is the proportion of subjects with favorable outcome on the Montreal Cognitive Assessment 90 days after aSAH. Data on safety, rescue therapy, delayed cerebral infarction, and health economics will be collected.
Trail registration
NCT02790632. |
| doi_str_mv | 10.1007/s12028-018-0575-z |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_journals_2919904793</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2919904793</sourcerecordid><originalsourceid>FETCH-LOGICAL-c372t-f5e9e6aa92cbc08c479bbf04dfd1613ab7bee56630cf838669d5792025b8436b3</originalsourceid><addsrcrecordid>eNp1Uk1v1DAQDQhES-EHcEEjcQFpA3Y-N9yWsGyR2t1Vu6gHhILjTBpXSRzsBMj-eibaUuDAwfaM_Oa9Gfs5zjPOXnPG4jeWe8ybu4zTCuPQ3d93jnkYRi5LIv5gigPuRonvHzmPrb1hzIuTOHzkHPmM8YDPg-N7X9NatUqKGnZG0b41utdS129hWwmL4M_gfKh7JbHt0czgQrSFbtQeixm810Neo_uOGCjb1kJirt1Ut73RdT0htsIIimp3ZfTQzWBZlqQlxxkQDVyKEvsRLvuhGCHVTSeMaq9huXJ5EnnQa7oinDAF6BJSYRA2xAdr1ehCdapFUC0sCurPwg_VV7BocTCjbQh0OeQkLqtWqwJOsdHGVOIa4fN6ebXbrF0PXv7Fc66k0aRPg9ZoJ-llW4lWIlyg1N_RjHBVqXpKi0FOXe42P5VU1P6ipIe5k1v_K_fqyxPnYSlqi09vzxPn04flLj11zzarj-nizJV-7PVuGWKCkRCJJ3PJ5jKIkzwvWVCUBY-4L_I4RwyjyGeynPvzKEqKME7o-8N8HvhR7p84Lw68ndHfBrR9dqMH05Jk5iU8SRgx-oTiBxSNa63BMuuMaoQZM86yyVPZwVMZeSqbPJXtqeb5LfOQN1jcVfw2EQG8A8B20wei-SP9f9Zf5NHcNw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2919904793</pqid></control><display><type>article</type><title>Clinical Trial Protocol: Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Efficacy, and Safety Study Comparing EG-1962 to Standard of Care Oral Nimodipine in Adults with Aneurysmal Subarachnoid Hemorrhage [NEWTON-2 (Nimodipine Microparticles to Enhance Recovery While Reducing TOxicity After SubarachNoid Hemorrhage)]</title><source>MEDLINE</source><source>ProQuest Central (Alumni Edition)</source><source>ProQuest Central UK/Ireland</source><source>SpringerNature Journals</source><source>ProQuest Central</source><creator>Hänggi, Daniel ; Etminan, Nima ; Mayer, Stephan A. ; Aldrich, E. Francois ; Diringer, Michael N. ; Schmutzhard, Erich ; Faleck, Herbert J. ; Ng, David ; Saville, Benjamin R. ; Macdonald, R. Loch</creator><creatorcontrib>Hänggi, Daniel ; Etminan, Nima ; Mayer, Stephan A. ; Aldrich, E. Francois ; Diringer, Michael N. ; Schmutzhard, Erich ; Faleck, Herbert J. ; Ng, David ; Saville, Benjamin R. ; Macdonald, R. Loch ; NEWTON Investigators ; for the NEWTON Investigators</creatorcontrib><description>Background
Nimodipine is the only drug approved in the treatment of aneurysmal subarachnoid hemorrhage (aSAH) in many countries. EG-1962, a product developed using the Precisa™ platform, is an extended-release microparticle formulation of nimodipine that can be administered intraventricularly or intracisternally. It was developed to test the hypothesis that delivering higher concentrations of extended-release nimodipine directly to the cerebrospinal fluid would provide superior efficacy compared to systemic administration.
Results
A Phase 1/2a multicenter, controlled, randomized, open-label, dose-escalation study determined the maximum tolerated dose and supported the safety and tolerability of EG-1962 in patients with aSAH. EG-1962, 600 mg, was selected for a pivotal, Phase 3 multicenter, randomized, double-blind, placebo-controlled, parallel-group efficacy, and safety study comparing it to standard of care oral nimodipine in adults with aSAH. Key inclusion criteria are patients with a ruptured saccular aneurysm repaired by clipping or coiling, World Federation of Neurological Surgeons grade 2–4, and modified Fisher score of > 1. Patients must have an external ventricular drain as part of standard of care. Patients are randomized to receive intraventricular investigational product (EG-1962 or NaCl solution) and an oral placebo or oral nimodipine in the approved dose regimen (active control) within 48 h of aSAH. The primary objective is to determine the efficacy of EG-1962 compared to oral nimodipine.
Conclusions
The primary endpoint is the proportion of subjects with favorable outcome (6–8) on the Extended Glasgow Outcome Scale assessed 90 days after aSAH. The secondary endpoint is the proportion of subjects with favorable outcome on the Montreal Cognitive Assessment 90 days after aSAH. Data on safety, rescue therapy, delayed cerebral infarction, and health economics will be collected.
Trail registration
NCT02790632.</description><identifier>ISSN: 1541-6933</identifier><identifier>EISSN: 1556-0961</identifier><identifier>DOI: 10.1007/s12028-018-0575-z</identifier><identifier>PMID: 30014184</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Adult ; Aged ; Calcium Channel Blockers - administration & dosage ; Calcium Channel Blockers - adverse effects ; Calcium Channel Blockers - pharmacology ; Cerebrospinal fluid ; Chromatography ; Clinical trials ; Clinical Trials, Phase III as Topic ; Critical Care Medicine ; Delayed-Action Preparations ; Double-Blind Method ; Female ; Glasgow Outcome Scale ; Hemorrhage ; Humans ; Hypotension ; Infusions, Intraventricular ; Intensive ; Internal Medicine ; Ischemia ; Male ; Medicine ; Medicine & Public Health ; Middle Aged ; Multicenter Studies as Topic ; NCT ; NCT02790632 ; Neurology ; Nimodipine - administration & dosage ; Nimodipine - adverse effects ; Nimodipine - pharmacology ; Original Article ; Outcome Assessment, Health Care ; Patients ; Pharmacokinetics ; Randomized Controlled Trials as Topic ; Standard of Care ; Subarachnoid Hemorrhage - drug therapy ; Toxicity</subject><ispartof>Neurocritical care, 2019-02, Vol.30 (1), p.88-97</ispartof><rights>Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society 2018</rights><rights>Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society 2018.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c372t-f5e9e6aa92cbc08c479bbf04dfd1613ab7bee56630cf838669d5792025b8436b3</citedby><cites>FETCH-LOGICAL-c372t-f5e9e6aa92cbc08c479bbf04dfd1613ab7bee56630cf838669d5792025b8436b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s12028-018-0575-z$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2919904793?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>315,782,786,21397,21398,27933,27934,33539,33753,41497,42566,43668,43814,51328,64394,64398,72478</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30014184$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hänggi, Daniel</creatorcontrib><creatorcontrib>Etminan, Nima</creatorcontrib><creatorcontrib>Mayer, Stephan A.</creatorcontrib><creatorcontrib>Aldrich, E. Francois</creatorcontrib><creatorcontrib>Diringer, Michael N.</creatorcontrib><creatorcontrib>Schmutzhard, Erich</creatorcontrib><creatorcontrib>Faleck, Herbert J.</creatorcontrib><creatorcontrib>Ng, David</creatorcontrib><creatorcontrib>Saville, Benjamin R.</creatorcontrib><creatorcontrib>Macdonald, R. Loch</creatorcontrib><creatorcontrib>NEWTON Investigators</creatorcontrib><creatorcontrib>for the NEWTON Investigators</creatorcontrib><title>Clinical Trial Protocol: Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Efficacy, and Safety Study Comparing EG-1962 to Standard of Care Oral Nimodipine in Adults with Aneurysmal Subarachnoid Hemorrhage [NEWTON-2 (Nimodipine Microparticles to Enhance Recovery While Reducing TOxicity After SubarachNoid Hemorrhage)]</title><title>Neurocritical care</title><addtitle>Neurocrit Care</addtitle><addtitle>Neurocrit Care</addtitle><description>Background
Nimodipine is the only drug approved in the treatment of aneurysmal subarachnoid hemorrhage (aSAH) in many countries. EG-1962, a product developed using the Precisa™ platform, is an extended-release microparticle formulation of nimodipine that can be administered intraventricularly or intracisternally. It was developed to test the hypothesis that delivering higher concentrations of extended-release nimodipine directly to the cerebrospinal fluid would provide superior efficacy compared to systemic administration.
Results
A Phase 1/2a multicenter, controlled, randomized, open-label, dose-escalation study determined the maximum tolerated dose and supported the safety and tolerability of EG-1962 in patients with aSAH. EG-1962, 600 mg, was selected for a pivotal, Phase 3 multicenter, randomized, double-blind, placebo-controlled, parallel-group efficacy, and safety study comparing it to standard of care oral nimodipine in adults with aSAH. Key inclusion criteria are patients with a ruptured saccular aneurysm repaired by clipping or coiling, World Federation of Neurological Surgeons grade 2–4, and modified Fisher score of > 1. Patients must have an external ventricular drain as part of standard of care. Patients are randomized to receive intraventricular investigational product (EG-1962 or NaCl solution) and an oral placebo or oral nimodipine in the approved dose regimen (active control) within 48 h of aSAH. The primary objective is to determine the efficacy of EG-1962 compared to oral nimodipine.
Conclusions
The primary endpoint is the proportion of subjects with favorable outcome (6–8) on the Extended Glasgow Outcome Scale assessed 90 days after aSAH. The secondary endpoint is the proportion of subjects with favorable outcome on the Montreal Cognitive Assessment 90 days after aSAH. Data on safety, rescue therapy, delayed cerebral infarction, and health economics will be collected.
Trail registration
NCT02790632.</description><subject>Adult</subject><subject>Aged</subject><subject>Calcium Channel Blockers - administration & dosage</subject><subject>Calcium Channel Blockers - adverse effects</subject><subject>Calcium Channel Blockers - pharmacology</subject><subject>Cerebrospinal fluid</subject><subject>Chromatography</subject><subject>Clinical trials</subject><subject>Clinical Trials, Phase III as Topic</subject><subject>Critical Care Medicine</subject><subject>Delayed-Action Preparations</subject><subject>Double-Blind Method</subject><subject>Female</subject><subject>Glasgow Outcome Scale</subject><subject>Hemorrhage</subject><subject>Humans</subject><subject>Hypotension</subject><subject>Infusions, Intraventricular</subject><subject>Intensive</subject><subject>Internal Medicine</subject><subject>Ischemia</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Middle Aged</subject><subject>Multicenter Studies as Topic</subject><subject>NCT</subject><subject>NCT02790632</subject><subject>Neurology</subject><subject>Nimodipine - administration & dosage</subject><subject>Nimodipine - adverse effects</subject><subject>Nimodipine - pharmacology</subject><subject>Original Article</subject><subject>Outcome Assessment, Health Care</subject><subject>Patients</subject><subject>Pharmacokinetics</subject><subject>Randomized Controlled Trials as Topic</subject><subject>Standard of Care</subject><subject>Subarachnoid Hemorrhage - drug therapy</subject><subject>Toxicity</subject><issn>1541-6933</issn><issn>1556-0961</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp1Uk1v1DAQDQhES-EHcEEjcQFpA3Y-N9yWsGyR2t1Vu6gHhILjTBpXSRzsBMj-eibaUuDAwfaM_Oa9Gfs5zjPOXnPG4jeWe8ybu4zTCuPQ3d93jnkYRi5LIv5gigPuRonvHzmPrb1hzIuTOHzkHPmM8YDPg-N7X9NatUqKGnZG0b41utdS129hWwmL4M_gfKh7JbHt0czgQrSFbtQeixm810Neo_uOGCjb1kJirt1Ut73RdT0htsIIimp3ZfTQzWBZlqQlxxkQDVyKEvsRLvuhGCHVTSeMaq9huXJ5EnnQa7oinDAF6BJSYRA2xAdr1ehCdapFUC0sCurPwg_VV7BocTCjbQh0OeQkLqtWqwJOsdHGVOIa4fN6ebXbrF0PXv7Fc66k0aRPg9ZoJ-llW4lWIlyg1N_RjHBVqXpKi0FOXe42P5VU1P6ipIe5k1v_K_fqyxPnYSlqi09vzxPn04flLj11zzarj-nizJV-7PVuGWKCkRCJJ3PJ5jKIkzwvWVCUBY-4L_I4RwyjyGeynPvzKEqKME7o-8N8HvhR7p84Lw68ndHfBrR9dqMH05Jk5iU8SRgx-oTiBxSNa63BMuuMaoQZM86yyVPZwVMZeSqbPJXtqeb5LfOQN1jcVfw2EQG8A8B20wei-SP9f9Zf5NHcNw</recordid><startdate>20190201</startdate><enddate>20190201</enddate><creator>Hänggi, Daniel</creator><creator>Etminan, Nima</creator><creator>Mayer, Stephan A.</creator><creator>Aldrich, E. Francois</creator><creator>Diringer, Michael N.</creator><creator>Schmutzhard, Erich</creator><creator>Faleck, Herbert J.</creator><creator>Ng, David</creator><creator>Saville, Benjamin R.</creator><creator>Macdonald, R. Loch</creator><general>Springer US</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope></search><sort><creationdate>20190201</creationdate><title>Clinical Trial Protocol: Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Efficacy, and Safety Study Comparing EG-1962 to Standard of Care Oral Nimodipine in Adults with Aneurysmal Subarachnoid Hemorrhage [NEWTON-2 (Nimodipine Microparticles to Enhance Recovery While Reducing TOxicity After SubarachNoid Hemorrhage)]</title><author>Hänggi, Daniel ; Etminan, Nima ; Mayer, Stephan A. ; Aldrich, E. Francois ; Diringer, Michael N. ; Schmutzhard, Erich ; Faleck, Herbert J. ; Ng, David ; Saville, Benjamin R. ; Macdonald, R. Loch</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c372t-f5e9e6aa92cbc08c479bbf04dfd1613ab7bee56630cf838669d5792025b8436b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Calcium Channel Blockers - administration & dosage</topic><topic>Calcium Channel Blockers - adverse effects</topic><topic>Calcium Channel Blockers - pharmacology</topic><topic>Cerebrospinal fluid</topic><topic>Chromatography</topic><topic>Clinical trials</topic><topic>Clinical Trials, Phase III as Topic</topic><topic>Critical Care Medicine</topic><topic>Delayed-Action Preparations</topic><topic>Double-Blind Method</topic><topic>Female</topic><topic>Glasgow Outcome Scale</topic><topic>Hemorrhage</topic><topic>Humans</topic><topic>Hypotension</topic><topic>Infusions, Intraventricular</topic><topic>Intensive</topic><topic>Internal Medicine</topic><topic>Ischemia</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Middle Aged</topic><topic>Multicenter Studies as Topic</topic><topic>NCT</topic><topic>NCT02790632</topic><topic>Neurology</topic><topic>Nimodipine - administration & dosage</topic><topic>Nimodipine - adverse effects</topic><topic>Nimodipine - pharmacology</topic><topic>Original Article</topic><topic>Outcome Assessment, Health Care</topic><topic>Patients</topic><topic>Pharmacokinetics</topic><topic>Randomized Controlled Trials as Topic</topic><topic>Standard of Care</topic><topic>Subarachnoid Hemorrhage - drug therapy</topic><topic>Toxicity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hänggi, Daniel</creatorcontrib><creatorcontrib>Etminan, Nima</creatorcontrib><creatorcontrib>Mayer, Stephan A.</creatorcontrib><creatorcontrib>Aldrich, E. Francois</creatorcontrib><creatorcontrib>Diringer, Michael N.</creatorcontrib><creatorcontrib>Schmutzhard, Erich</creatorcontrib><creatorcontrib>Faleck, Herbert J.</creatorcontrib><creatorcontrib>Ng, David</creatorcontrib><creatorcontrib>Saville, Benjamin R.</creatorcontrib><creatorcontrib>Macdonald, R. Loch</creatorcontrib><creatorcontrib>NEWTON Investigators</creatorcontrib><creatorcontrib>for the NEWTON Investigators</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Proquest Nursing & Allied Health Source</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><jtitle>Neurocritical care</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hänggi, Daniel</au><au>Etminan, Nima</au><au>Mayer, Stephan A.</au><au>Aldrich, E. Francois</au><au>Diringer, Michael N.</au><au>Schmutzhard, Erich</au><au>Faleck, Herbert J.</au><au>Ng, David</au><au>Saville, Benjamin R.</au><au>Macdonald, R. Loch</au><aucorp>NEWTON Investigators</aucorp><aucorp>for the NEWTON Investigators</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Clinical Trial Protocol: Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Efficacy, and Safety Study Comparing EG-1962 to Standard of Care Oral Nimodipine in Adults with Aneurysmal Subarachnoid Hemorrhage [NEWTON-2 (Nimodipine Microparticles to Enhance Recovery While Reducing TOxicity After SubarachNoid Hemorrhage)]</atitle><jtitle>Neurocritical care</jtitle><stitle>Neurocrit Care</stitle><addtitle>Neurocrit Care</addtitle><date>2019-02-01</date><risdate>2019</risdate><volume>30</volume><issue>1</issue><spage>88</spage><epage>97</epage><pages>88-97</pages><issn>1541-6933</issn><eissn>1556-0961</eissn><abstract>Background
Nimodipine is the only drug approved in the treatment of aneurysmal subarachnoid hemorrhage (aSAH) in many countries. EG-1962, a product developed using the Precisa™ platform, is an extended-release microparticle formulation of nimodipine that can be administered intraventricularly or intracisternally. It was developed to test the hypothesis that delivering higher concentrations of extended-release nimodipine directly to the cerebrospinal fluid would provide superior efficacy compared to systemic administration.
Results
A Phase 1/2a multicenter, controlled, randomized, open-label, dose-escalation study determined the maximum tolerated dose and supported the safety and tolerability of EG-1962 in patients with aSAH. EG-1962, 600 mg, was selected for a pivotal, Phase 3 multicenter, randomized, double-blind, placebo-controlled, parallel-group efficacy, and safety study comparing it to standard of care oral nimodipine in adults with aSAH. Key inclusion criteria are patients with a ruptured saccular aneurysm repaired by clipping or coiling, World Federation of Neurological Surgeons grade 2–4, and modified Fisher score of > 1. Patients must have an external ventricular drain as part of standard of care. Patients are randomized to receive intraventricular investigational product (EG-1962 or NaCl solution) and an oral placebo or oral nimodipine in the approved dose regimen (active control) within 48 h of aSAH. The primary objective is to determine the efficacy of EG-1962 compared to oral nimodipine.
Conclusions
The primary endpoint is the proportion of subjects with favorable outcome (6–8) on the Extended Glasgow Outcome Scale assessed 90 days after aSAH. The secondary endpoint is the proportion of subjects with favorable outcome on the Montreal Cognitive Assessment 90 days after aSAH. Data on safety, rescue therapy, delayed cerebral infarction, and health economics will be collected.
Trail registration
NCT02790632.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>30014184</pmid><doi>10.1007/s12028-018-0575-z</doi><tpages>10</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1541-6933 |
| ispartof | Neurocritical care, 2019-02, Vol.30 (1), p.88-97 |
| issn | 1541-6933 1556-0961 |
| language | eng |
| recordid | cdi_proquest_journals_2919904793 |
| source | MEDLINE; ProQuest Central (Alumni Edition); ProQuest Central UK/Ireland; SpringerNature Journals; ProQuest Central |
| subjects | Adult Aged Calcium Channel Blockers - administration & dosage Calcium Channel Blockers - adverse effects Calcium Channel Blockers - pharmacology Cerebrospinal fluid Chromatography Clinical trials Clinical Trials, Phase III as Topic Critical Care Medicine Delayed-Action Preparations Double-Blind Method Female Glasgow Outcome Scale Hemorrhage Humans Hypotension Infusions, Intraventricular Intensive Internal Medicine Ischemia Male Medicine Medicine & Public Health Middle Aged Multicenter Studies as Topic NCT NCT02790632 Neurology Nimodipine - administration & dosage Nimodipine - adverse effects Nimodipine - pharmacology Original Article Outcome Assessment, Health Care Patients Pharmacokinetics Randomized Controlled Trials as Topic Standard of Care Subarachnoid Hemorrhage - drug therapy Toxicity |
| title | Clinical Trial Protocol: Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Efficacy, and Safety Study Comparing EG-1962 to Standard of Care Oral Nimodipine in Adults with Aneurysmal Subarachnoid Hemorrhage [NEWTON-2 (Nimodipine Microparticles to Enhance Recovery While Reducing TOxicity After SubarachNoid Hemorrhage)] |
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