Loading…
Pharmacokinetic and pharmacodynamic bioequivalence of biosimilar MYL‐1601D with US and European insulin aspart in healthy volunteers: A randomized, double‐blind, crossover, euglycaemic glucose clamp study
Aim To evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) bioequivalence (BE) of MYL‐1601D biosimilar with originator, NovoLog (Ref‐InsAsp‐US), and NovoRapid (Ref‐InsAsp‐EU). Materials and Methods This was a double‐blind, randomized, crossover study that enrolled 71 healthy subjects to recei...
Saved in:
| Published in: | Diabetes, obesity & metabolism obesity & metabolism, 2021-12, Vol.23 (12), p.2670-2678 |
|---|---|
| Main Authors: | , , , , , , , , , |
| Format: | Article |
| Language: | English |
| Subjects: | |
| Citations: | Items that this one cites Items that cite this one |
| Online Access: | Get full text |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| cited_by | cdi_FETCH-LOGICAL-c4439-8f6009d5386af8f178f8d93bce649855b0f0403324a7d3f0a25f9256f90e6b583 |
|---|---|
| cites | cdi_FETCH-LOGICAL-c4439-8f6009d5386af8f178f8d93bce649855b0f0403324a7d3f0a25f9256f90e6b583 |
| container_end_page | 2678 |
| container_issue | 12 |
| container_start_page | 2670 |
| container_title | Diabetes, obesity & metabolism |
| container_volume | 23 |
| creator | Hövelmann, Ulrike Raiter, Yaron Chullikana, Anoop Liu, Mark Donnelly, Charles Lawrence, Tracey Sengupta, Nilanjan CL, Gopu Ranganna, Gopinath Barve, Abhijit |
| description | Aim
To evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) bioequivalence (BE) of MYL‐1601D biosimilar with originator, NovoLog (Ref‐InsAsp‐US), and NovoRapid (Ref‐InsAsp‐EU).
Materials and Methods
This was a double‐blind, randomized, crossover study that enrolled 71 healthy subjects to receive a single subcutaneous dose (0.2 U/kg) of each formulation under automated euglycaemic clamp conditions (ClampArt, level 81 mg/dL, duration 12 hours postdose). Primary PK endpoints were area under the plasma insulin aspart concentration‐time curve from 0 to 12 hours (AUC0‐12h) and maximum plasma insulin aspart concentration (Cmax). Primary PD endpoints were area under the glucose infusion rate (GIR) time curve from 0 to 12 hours (AUCGIR0‐12h) and maximum GIR (GIRmax). Insulin aspart in plasma was quantified using immunoaffinity purification followed by ultraperformance liquid chromatography and tandem mass spectrometric detection. The pairwise comparisons of geometric least square mean (LS‐mean) ratio for a 90% confidence interval (CI) of primary PK, and 90% CIs (MYL‐1601D vs. Ref‐InsAsp‐US) and 95% CIs (MYL‐1601D vs. Ref‐InsAsp‐EU) of primary PD variables, were to be within 80% to 125% to show BE.
Results
MYL‐1601D showed PK BE to both Ref‐InsAsp‐US (AUC0‐12h geometric LS‐mean ratio 102.17, 90% CI [100.26; 104.11]; Cmax 106.13 [100.71; 111.85]) and Ref‐InsAsp‐EU (AUC0‐12h 101.84 [100.04; 103.67]; Cmax 105.74 [101.09; 110.60]). Likewise, MYL‐1601D showed PD BE to Ref‐InsAsp‐US (AUCGIR_0‐last 99.93; 90% CI [95.74; 104.30]; GIR_max 100.12 [94.46; 106.12]) and Ref‐InsAsp‐EU (AUCGIR_0‐last 96.42; 95% CI [91.17; 101.98]; GIR_max 95.10 [89.37; 101.19]). All three insulin aspart products were well tolerated.
Conclusion
MYL‐1601D showed BE to Ref‐InsAsp‐US and Ref‐InsAsp‐EU with a comparable safety profile. |
| doi_str_mv | 10.1111/dom.14519 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_9292719</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2594369366</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4439-8f6009d5386af8f178f8d93bce649855b0f0403324a7d3f0a25f9256f90e6b583</originalsourceid><addsrcrecordid>eNp1ks1u1DAQxyMEoqVw4AWQJS4gNa0dJ16bA1LVlg9pqyJBD5wix5nsujh2asdbhROPwKPxDDwJ3g8qQMIXe8a_-fvv0WTZU4KPSFrHreuPSFkRcS_bJyWjOaEFu785FzkXuNjLHoVwjTEuKZ89zPZoSWecM7Kf_fiwlL6Xyn3RFkatkLQtGna5drKyT7lGO7iJeiUNWAXIdetM0L020qOLz_Of374ThskZutXjEl193IicR-8GkBZpG6LRFskwSD-mEC1BmnE5oZUz0Y4APrxCJ8inKtfrr9AeotbFxkDSbVJlipV3IbgV-EMEcWEmJWFtbGGicgGQMrIfUBhjOz3OHnTSBHiy2w-yqzfnn07f5fPLt-9PT-a5Kksqct4xjEVbUc5kxzsy4x1vBW0UsFLwqmpwh0tMaVHKWUs7LIuqE0XFOoGBNRWnB9nrre4Qmx5aBXb00tSD1730U-2krv--sXpZL9yqFoUoZkQkgRc7Ae9uIoSx7nVQYIy04GKo02O4EJwSnNDn_6DXLnqbvpcoUVImKGOJermlNs3y0N2ZIbhez0md2ltv5iSxz_50f0f-HowEHG-BW21g-r9SfXZ5sZX8BUWfzb8</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2594369366</pqid></control><display><type>article</type><title>Pharmacokinetic and pharmacodynamic bioequivalence of biosimilar MYL‐1601D with US and European insulin aspart in healthy volunteers: A randomized, double‐blind, crossover, euglycaemic glucose clamp study</title><source>Wiley-Blackwell Journals</source><creator>Hövelmann, Ulrike ; Raiter, Yaron ; Chullikana, Anoop ; Liu, Mark ; Donnelly, Charles ; Lawrence, Tracey ; Sengupta, Nilanjan ; CL, Gopu ; Ranganna, Gopinath ; Barve, Abhijit</creator><creatorcontrib>Hövelmann, Ulrike ; Raiter, Yaron ; Chullikana, Anoop ; Liu, Mark ; Donnelly, Charles ; Lawrence, Tracey ; Sengupta, Nilanjan ; CL, Gopu ; Ranganna, Gopinath ; Barve, Abhijit</creatorcontrib><description>Aim
To evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) bioequivalence (BE) of MYL‐1601D biosimilar with originator, NovoLog (Ref‐InsAsp‐US), and NovoRapid (Ref‐InsAsp‐EU).
Materials and Methods
This was a double‐blind, randomized, crossover study that enrolled 71 healthy subjects to receive a single subcutaneous dose (0.2 U/kg) of each formulation under automated euglycaemic clamp conditions (ClampArt, level 81 mg/dL, duration 12 hours postdose). Primary PK endpoints were area under the plasma insulin aspart concentration‐time curve from 0 to 12 hours (AUC0‐12h) and maximum plasma insulin aspart concentration (Cmax). Primary PD endpoints were area under the glucose infusion rate (GIR) time curve from 0 to 12 hours (AUCGIR0‐12h) and maximum GIR (GIRmax). Insulin aspart in plasma was quantified using immunoaffinity purification followed by ultraperformance liquid chromatography and tandem mass spectrometric detection. The pairwise comparisons of geometric least square mean (LS‐mean) ratio for a 90% confidence interval (CI) of primary PK, and 90% CIs (MYL‐1601D vs. Ref‐InsAsp‐US) and 95% CIs (MYL‐1601D vs. Ref‐InsAsp‐EU) of primary PD variables, were to be within 80% to 125% to show BE.
Results
MYL‐1601D showed PK BE to both Ref‐InsAsp‐US (AUC0‐12h geometric LS‐mean ratio 102.17, 90% CI [100.26; 104.11]; Cmax 106.13 [100.71; 111.85]) and Ref‐InsAsp‐EU (AUC0‐12h 101.84 [100.04; 103.67]; Cmax 105.74 [101.09; 110.60]). Likewise, MYL‐1601D showed PD BE to Ref‐InsAsp‐US (AUCGIR_0‐last 99.93; 90% CI [95.74; 104.30]; GIR_max 100.12 [94.46; 106.12]) and Ref‐InsAsp‐EU (AUCGIR_0‐last 96.42; 95% CI [91.17; 101.98]; GIR_max 95.10 [89.37; 101.19]). All three insulin aspart products were well tolerated.
Conclusion
MYL‐1601D showed BE to Ref‐InsAsp‐US and Ref‐InsAsp‐EU with a comparable safety profile.</description><identifier>ISSN: 1462-8902</identifier><identifier>ISSN: 1463-1326</identifier><identifier>EISSN: 1463-1326</identifier><identifier>DOI: 10.1111/dom.14519</identifier><identifier>PMID: 34378861</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Area Under Curve ; Bioequivalence ; Biological products ; biosimilar ; Biosimilar Pharmaceuticals - adverse effects ; Cross-Over Studies ; Diabetes ; Double-Blind Method ; Double-blind studies ; euglycaemic clamp study ; Glucose ; Glucose Clamp Technique ; Healthy Volunteers ; Humans ; Hypoglycemic Agents ; Insulin ; Insulin Aspart ; Liquid chromatography ; Original ; Pharmacodynamics ; Pharmacokinetics ; pharmacokinetics/pharmacodynamics ; Therapeutic Equivalency</subject><ispartof>Diabetes, obesity & metabolism, 2021-12, Vol.23 (12), p.2670-2678</ispartof><rights>2021 The Authors. published by John Wiley & Sons Ltd.</rights><rights>2021 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.</rights><rights>2021. This article is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4439-8f6009d5386af8f178f8d93bce649855b0f0403324a7d3f0a25f9256f90e6b583</citedby><cites>FETCH-LOGICAL-c4439-8f6009d5386af8f178f8d93bce649855b0f0403324a7d3f0a25f9256f90e6b583</cites><orcidid>0000-0001-9974-3354 ; 0000-0002-1315-2017 ; 0000-0002-0940-8972</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fdom.14519$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fdom.14519$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>230,315,786,790,891,27957,27958,50923,51032</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34378861$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hövelmann, Ulrike</creatorcontrib><creatorcontrib>Raiter, Yaron</creatorcontrib><creatorcontrib>Chullikana, Anoop</creatorcontrib><creatorcontrib>Liu, Mark</creatorcontrib><creatorcontrib>Donnelly, Charles</creatorcontrib><creatorcontrib>Lawrence, Tracey</creatorcontrib><creatorcontrib>Sengupta, Nilanjan</creatorcontrib><creatorcontrib>CL, Gopu</creatorcontrib><creatorcontrib>Ranganna, Gopinath</creatorcontrib><creatorcontrib>Barve, Abhijit</creatorcontrib><title>Pharmacokinetic and pharmacodynamic bioequivalence of biosimilar MYL‐1601D with US and European insulin aspart in healthy volunteers: A randomized, double‐blind, crossover, euglycaemic glucose clamp study</title><title>Diabetes, obesity & metabolism</title><addtitle>Diabetes Obes Metab</addtitle><description>Aim
To evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) bioequivalence (BE) of MYL‐1601D biosimilar with originator, NovoLog (Ref‐InsAsp‐US), and NovoRapid (Ref‐InsAsp‐EU).
Materials and Methods
This was a double‐blind, randomized, crossover study that enrolled 71 healthy subjects to receive a single subcutaneous dose (0.2 U/kg) of each formulation under automated euglycaemic clamp conditions (ClampArt, level 81 mg/dL, duration 12 hours postdose). Primary PK endpoints were area under the plasma insulin aspart concentration‐time curve from 0 to 12 hours (AUC0‐12h) and maximum plasma insulin aspart concentration (Cmax). Primary PD endpoints were area under the glucose infusion rate (GIR) time curve from 0 to 12 hours (AUCGIR0‐12h) and maximum GIR (GIRmax). Insulin aspart in plasma was quantified using immunoaffinity purification followed by ultraperformance liquid chromatography and tandem mass spectrometric detection. The pairwise comparisons of geometric least square mean (LS‐mean) ratio for a 90% confidence interval (CI) of primary PK, and 90% CIs (MYL‐1601D vs. Ref‐InsAsp‐US) and 95% CIs (MYL‐1601D vs. Ref‐InsAsp‐EU) of primary PD variables, were to be within 80% to 125% to show BE.
Results
MYL‐1601D showed PK BE to both Ref‐InsAsp‐US (AUC0‐12h geometric LS‐mean ratio 102.17, 90% CI [100.26; 104.11]; Cmax 106.13 [100.71; 111.85]) and Ref‐InsAsp‐EU (AUC0‐12h 101.84 [100.04; 103.67]; Cmax 105.74 [101.09; 110.60]). Likewise, MYL‐1601D showed PD BE to Ref‐InsAsp‐US (AUCGIR_0‐last 99.93; 90% CI [95.74; 104.30]; GIR_max 100.12 [94.46; 106.12]) and Ref‐InsAsp‐EU (AUCGIR_0‐last 96.42; 95% CI [91.17; 101.98]; GIR_max 95.10 [89.37; 101.19]). All three insulin aspart products were well tolerated.
Conclusion
MYL‐1601D showed BE to Ref‐InsAsp‐US and Ref‐InsAsp‐EU with a comparable safety profile.</description><subject>Area Under Curve</subject><subject>Bioequivalence</subject><subject>Biological products</subject><subject>biosimilar</subject><subject>Biosimilar Pharmaceuticals - adverse effects</subject><subject>Cross-Over Studies</subject><subject>Diabetes</subject><subject>Double-Blind Method</subject><subject>Double-blind studies</subject><subject>euglycaemic clamp study</subject><subject>Glucose</subject><subject>Glucose Clamp Technique</subject><subject>Healthy Volunteers</subject><subject>Humans</subject><subject>Hypoglycemic Agents</subject><subject>Insulin</subject><subject>Insulin Aspart</subject><subject>Liquid chromatography</subject><subject>Original</subject><subject>Pharmacodynamics</subject><subject>Pharmacokinetics</subject><subject>pharmacokinetics/pharmacodynamics</subject><subject>Therapeutic Equivalency</subject><issn>1462-8902</issn><issn>1463-1326</issn><issn>1463-1326</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><recordid>eNp1ks1u1DAQxyMEoqVw4AWQJS4gNa0dJ16bA1LVlg9pqyJBD5wix5nsujh2asdbhROPwKPxDDwJ3g8qQMIXe8a_-fvv0WTZU4KPSFrHreuPSFkRcS_bJyWjOaEFu785FzkXuNjLHoVwjTEuKZ89zPZoSWecM7Kf_fiwlL6Xyn3RFkatkLQtGna5drKyT7lGO7iJeiUNWAXIdetM0L020qOLz_Of374ThskZutXjEl193IicR-8GkBZpG6LRFskwSD-mEC1BmnE5oZUz0Y4APrxCJ8inKtfrr9AeotbFxkDSbVJlipV3IbgV-EMEcWEmJWFtbGGicgGQMrIfUBhjOz3OHnTSBHiy2w-yqzfnn07f5fPLt-9PT-a5Kksqct4xjEVbUc5kxzsy4x1vBW0UsFLwqmpwh0tMaVHKWUs7LIuqE0XFOoGBNRWnB9nrre4Qmx5aBXb00tSD1730U-2krv--sXpZL9yqFoUoZkQkgRc7Ae9uIoSx7nVQYIy04GKo02O4EJwSnNDn_6DXLnqbvpcoUVImKGOJermlNs3y0N2ZIbhez0md2ltv5iSxz_50f0f-HowEHG-BW21g-r9SfXZ5sZX8BUWfzb8</recordid><startdate>202112</startdate><enddate>202112</enddate><creator>Hövelmann, Ulrike</creator><creator>Raiter, Yaron</creator><creator>Chullikana, Anoop</creator><creator>Liu, Mark</creator><creator>Donnelly, Charles</creator><creator>Lawrence, Tracey</creator><creator>Sengupta, Nilanjan</creator><creator>CL, Gopu</creator><creator>Ranganna, Gopinath</creator><creator>Barve, Abhijit</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</general><scope>24P</scope><scope>WIN</scope><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>7T5</scope><scope>7TK</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-9974-3354</orcidid><orcidid>https://orcid.org/0000-0002-1315-2017</orcidid><orcidid>https://orcid.org/0000-0002-0940-8972</orcidid></search><sort><creationdate>202112</creationdate><title>Pharmacokinetic and pharmacodynamic bioequivalence of biosimilar MYL‐1601D with US and European insulin aspart in healthy volunteers: A randomized, double‐blind, crossover, euglycaemic glucose clamp study</title><author>Hövelmann, Ulrike ; Raiter, Yaron ; Chullikana, Anoop ; Liu, Mark ; Donnelly, Charles ; Lawrence, Tracey ; Sengupta, Nilanjan ; CL, Gopu ; Ranganna, Gopinath ; Barve, Abhijit</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4439-8f6009d5386af8f178f8d93bce649855b0f0403324a7d3f0a25f9256f90e6b583</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Area Under Curve</topic><topic>Bioequivalence</topic><topic>Biological products</topic><topic>biosimilar</topic><topic>Biosimilar Pharmaceuticals - adverse effects</topic><topic>Cross-Over Studies</topic><topic>Diabetes</topic><topic>Double-Blind Method</topic><topic>Double-blind studies</topic><topic>euglycaemic clamp study</topic><topic>Glucose</topic><topic>Glucose Clamp Technique</topic><topic>Healthy Volunteers</topic><topic>Humans</topic><topic>Hypoglycemic Agents</topic><topic>Insulin</topic><topic>Insulin Aspart</topic><topic>Liquid chromatography</topic><topic>Original</topic><topic>Pharmacodynamics</topic><topic>Pharmacokinetics</topic><topic>pharmacokinetics/pharmacodynamics</topic><topic>Therapeutic Equivalency</topic><toplevel>online_resources</toplevel><creatorcontrib>Hövelmann, Ulrike</creatorcontrib><creatorcontrib>Raiter, Yaron</creatorcontrib><creatorcontrib>Chullikana, Anoop</creatorcontrib><creatorcontrib>Liu, Mark</creatorcontrib><creatorcontrib>Donnelly, Charles</creatorcontrib><creatorcontrib>Lawrence, Tracey</creatorcontrib><creatorcontrib>Sengupta, Nilanjan</creatorcontrib><creatorcontrib>CL, Gopu</creatorcontrib><creatorcontrib>Ranganna, Gopinath</creatorcontrib><creatorcontrib>Barve, Abhijit</creatorcontrib><collection>Wiley Online Library</collection><collection>Wiley Online Library</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Diabetes, obesity & metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hövelmann, Ulrike</au><au>Raiter, Yaron</au><au>Chullikana, Anoop</au><au>Liu, Mark</au><au>Donnelly, Charles</au><au>Lawrence, Tracey</au><au>Sengupta, Nilanjan</au><au>CL, Gopu</au><au>Ranganna, Gopinath</au><au>Barve, Abhijit</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pharmacokinetic and pharmacodynamic bioequivalence of biosimilar MYL‐1601D with US and European insulin aspart in healthy volunteers: A randomized, double‐blind, crossover, euglycaemic glucose clamp study</atitle><jtitle>Diabetes, obesity & metabolism</jtitle><addtitle>Diabetes Obes Metab</addtitle><date>2021-12</date><risdate>2021</risdate><volume>23</volume><issue>12</issue><spage>2670</spage><epage>2678</epage><pages>2670-2678</pages><issn>1462-8902</issn><issn>1463-1326</issn><eissn>1463-1326</eissn><notes>st</notes><notes>Scientific Sessions of the American Diabetes Association, held 25‐29 June 2021.</notes><notes>A part of this study's data were presented as a poster presentation at the virtual 81</notes><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><notes>ObjectType-Undefined-3</notes><notes>A part of this study's data were presented as a poster presentation at the virtual 81st Scientific Sessions of the American Diabetes Association, held 25‐29 June 2021.</notes><abstract>Aim
To evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) bioequivalence (BE) of MYL‐1601D biosimilar with originator, NovoLog (Ref‐InsAsp‐US), and NovoRapid (Ref‐InsAsp‐EU).
Materials and Methods
This was a double‐blind, randomized, crossover study that enrolled 71 healthy subjects to receive a single subcutaneous dose (0.2 U/kg) of each formulation under automated euglycaemic clamp conditions (ClampArt, level 81 mg/dL, duration 12 hours postdose). Primary PK endpoints were area under the plasma insulin aspart concentration‐time curve from 0 to 12 hours (AUC0‐12h) and maximum plasma insulin aspart concentration (Cmax). Primary PD endpoints were area under the glucose infusion rate (GIR) time curve from 0 to 12 hours (AUCGIR0‐12h) and maximum GIR (GIRmax). Insulin aspart in plasma was quantified using immunoaffinity purification followed by ultraperformance liquid chromatography and tandem mass spectrometric detection. The pairwise comparisons of geometric least square mean (LS‐mean) ratio for a 90% confidence interval (CI) of primary PK, and 90% CIs (MYL‐1601D vs. Ref‐InsAsp‐US) and 95% CIs (MYL‐1601D vs. Ref‐InsAsp‐EU) of primary PD variables, were to be within 80% to 125% to show BE.
Results
MYL‐1601D showed PK BE to both Ref‐InsAsp‐US (AUC0‐12h geometric LS‐mean ratio 102.17, 90% CI [100.26; 104.11]; Cmax 106.13 [100.71; 111.85]) and Ref‐InsAsp‐EU (AUC0‐12h 101.84 [100.04; 103.67]; Cmax 105.74 [101.09; 110.60]). Likewise, MYL‐1601D showed PD BE to Ref‐InsAsp‐US (AUCGIR_0‐last 99.93; 90% CI [95.74; 104.30]; GIR_max 100.12 [94.46; 106.12]) and Ref‐InsAsp‐EU (AUCGIR_0‐last 96.42; 95% CI [91.17; 101.98]; GIR_max 95.10 [89.37; 101.19]). All three insulin aspart products were well tolerated.
Conclusion
MYL‐1601D showed BE to Ref‐InsAsp‐US and Ref‐InsAsp‐EU with a comparable safety profile.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>34378861</pmid><doi>10.1111/dom.14519</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0001-9974-3354</orcidid><orcidid>https://orcid.org/0000-0002-1315-2017</orcidid><orcidid>https://orcid.org/0000-0002-0940-8972</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1462-8902 |
| ispartof | Diabetes, obesity & metabolism, 2021-12, Vol.23 (12), p.2670-2678 |
| issn | 1462-8902 1463-1326 1463-1326 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_9292719 |
| source | Wiley-Blackwell Journals |
| subjects | Area Under Curve Bioequivalence Biological products biosimilar Biosimilar Pharmaceuticals - adverse effects Cross-Over Studies Diabetes Double-Blind Method Double-blind studies euglycaemic clamp study Glucose Glucose Clamp Technique Healthy Volunteers Humans Hypoglycemic Agents Insulin Insulin Aspart Liquid chromatography Original Pharmacodynamics Pharmacokinetics pharmacokinetics/pharmacodynamics Therapeutic Equivalency |
| title | Pharmacokinetic and pharmacodynamic bioequivalence of biosimilar MYL‐1601D with US and European insulin aspart in healthy volunteers: A randomized, double‐blind, crossover, euglycaemic glucose clamp study |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-09-22T14%3A33%3A09IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Pharmacokinetic%20and%20pharmacodynamic%20bioequivalence%20of%20biosimilar%20MYL%E2%80%901601D%20with%20US%20and%20European%20insulin%20aspart%20in%20healthy%20volunteers:%20A%20randomized,%20double%E2%80%90blind,%20crossover,%20euglycaemic%20glucose%20clamp%20study&rft.jtitle=Diabetes,%20obesity%20&%20metabolism&rft.au=H%C3%B6velmann,%20Ulrike&rft.date=2021-12&rft.volume=23&rft.issue=12&rft.spage=2670&rft.epage=2678&rft.pages=2670-2678&rft.issn=1462-8902&rft.eissn=1463-1326&rft_id=info:doi/10.1111/dom.14519&rft_dat=%3Cproquest_pubme%3E2594369366%3C/proquest_pubme%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c4439-8f6009d5386af8f178f8d93bce649855b0f0403324a7d3f0a25f9256f90e6b583%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2594369366&rft_id=info:pmid/34378861&rfr_iscdi=true |