Pharmacokinetics, Pharmacodynamics, and Safety of Dulaglutide After Single or Multiple Doses in Chinese Healthy Subjects and Patients with T2DM: A Randomized, Placebo-Controlled, Phase I Study
Introduction This study evaluated the pharmacokinetics, pharmacodynamics, and safety of a single dulaglutide dose in Chinese healthy subjects and of multiple dulaglutide doses in Chinese patients with type 2 diabetes mellitus (T2DM). Methods This two-part, double-blind, placebo-controlled study incl...
Ausführliche Beschreibung
Autor*in: |
Xu, Junyu [verfasserIn] |
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E-Artikel |
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Englisch |
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2021 |
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Anmerkung: |
© The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature 2021 |
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Übergeordnetes Werk: |
Enthalten in: Advances in therapy - Tarporley : Springer Healthcare Communications, 2000, 39(2021), 1 vom: 17. Nov., Seite 488-503 |
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Übergeordnetes Werk: |
volume:39 ; year:2021 ; number:1 ; day:17 ; month:11 ; pages:488-503 |
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DOI / URN: |
10.1007/s12325-021-01921-5 |
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SPR046085459 |
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245 | 1 | 0 | |a Pharmacokinetics, Pharmacodynamics, and Safety of Dulaglutide After Single or Multiple Doses in Chinese Healthy Subjects and Patients with T2DM: A Randomized, Placebo-Controlled, Phase I Study |
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520 | |a Introduction This study evaluated the pharmacokinetics, pharmacodynamics, and safety of a single dulaglutide dose in Chinese healthy subjects and of multiple dulaglutide doses in Chinese patients with type 2 diabetes mellitus (T2DM). Methods This two-part, double-blind, placebo-controlled study included 16 healthy subjects randomized to receive a single dose of placebo and two of three dulaglutide doses (0.5 mg, 0.75 mg, or 1.5 mg) in three treatment periods, and 42 patients with T2DM randomized to receive placebo or one of the three dulaglutide doses once weekly for 4 weeks. Pharmacokinetics and safety parameters were assessed in all participants, and pharmacodynamics effects were investigated in patients with T2DM. Results Following a single-dose administration of 0.5 mg, 0.75 mg, or 1.5 mg dulaglutide in healthy subjects, geometric mean maximum concentrations (Cmax) were 29.4, 44.2, and 81.5 ng/mL, respectively. Following weekly administration in patients with T2DM for 4 weeks, Cmax were 26.3, 41.4, and 70.2 ng/mL, respectively, with accumulation ratios of 1.33–1.39. Geometric mean for half-life of 4–5 days and median time to Cmax (tmax) of approximately 48 h were observed in both study populations. Dose-proportional increases in drug exposure were observed after both single and multiple dosing. Significant reductions in baseline-corrected fasting glucose and hemoglobin A1c (HbA1c) were observed in patients with T2DM who received dulaglutide 0.75 mg and 1.5 mg. Dulaglutide was well tolerated, with the majority of adverse events being gastrointestinal disorders of mild severity. Conclusions Pharmacokinetics, pharmacodynamics, and safety profiles of dulaglutide demonstrated in the present study support a once-weekly dosing regimen in Chinese patients with T2DM. Trial Registration NCT01667900 (ClinicalTrials.gov). | ||
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700 | 1 | |a Loghin, Corina |4 aut | |
700 | 1 | |a Tham, Lai San |4 aut | |
700 | 1 | |a Cui, Xuewei |4 aut | |
700 | 1 | |a Cui, Yimin |0 (orcid)0000-0002-4186-1005 |4 aut | |
700 | 1 | |a Wang, Weiqing |4 aut | |
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10.1007/s12325-021-01921-5 doi (DE-627)SPR046085459 (SPR)s12325-021-01921-5-e DE-627 ger DE-627 rakwb eng Xu, Junyu verfasserin aut Pharmacokinetics, Pharmacodynamics, and Safety of Dulaglutide After Single or Multiple Doses in Chinese Healthy Subjects and Patients with T2DM: A Randomized, Placebo-Controlled, Phase I Study 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature 2021 Introduction This study evaluated the pharmacokinetics, pharmacodynamics, and safety of a single dulaglutide dose in Chinese healthy subjects and of multiple dulaglutide doses in Chinese patients with type 2 diabetes mellitus (T2DM). Methods This two-part, double-blind, placebo-controlled study included 16 healthy subjects randomized to receive a single dose of placebo and two of three dulaglutide doses (0.5 mg, 0.75 mg, or 1.5 mg) in three treatment periods, and 42 patients with T2DM randomized to receive placebo or one of the three dulaglutide doses once weekly for 4 weeks. Pharmacokinetics and safety parameters were assessed in all participants, and pharmacodynamics effects were investigated in patients with T2DM. Results Following a single-dose administration of 0.5 mg, 0.75 mg, or 1.5 mg dulaglutide in healthy subjects, geometric mean maximum concentrations (Cmax) were 29.4, 44.2, and 81.5 ng/mL, respectively. Following weekly administration in patients with T2DM for 4 weeks, Cmax were 26.3, 41.4, and 70.2 ng/mL, respectively, with accumulation ratios of 1.33–1.39. Geometric mean for half-life of 4–5 days and median time to Cmax (tmax) of approximately 48 h were observed in both study populations. Dose-proportional increases in drug exposure were observed after both single and multiple dosing. Significant reductions in baseline-corrected fasting glucose and hemoglobin A1c (HbA1c) were observed in patients with T2DM who received dulaglutide 0.75 mg and 1.5 mg. Dulaglutide was well tolerated, with the majority of adverse events being gastrointestinal disorders of mild severity. Conclusions Pharmacokinetics, pharmacodynamics, and safety profiles of dulaglutide demonstrated in the present study support a once-weekly dosing regimen in Chinese patients with T2DM. Trial Registration NCT01667900 (ClinicalTrials.gov). Dulaglutide (dpeaa)DE-He213 Phase I study (dpeaa)DE-He213 Chinese participants (dpeaa)DE-He213 Zhang, Yifei aut Li, Yiming aut Zhao, Xia aut Zhou, Weiwei aut Loghin, Corina aut Tham, Lai San aut Cui, Xuewei aut Cui, Yimin (orcid)0000-0002-4186-1005 aut Wang, Weiqing aut Enthalten in Advances in therapy Tarporley : Springer Healthcare Communications, 2000 39(2021), 1 vom: 17. Nov., Seite 488-503 (DE-627)563170433 (DE-600)2421646-X 1865-8652 nnns volume:39 year:2021 number:1 day:17 month:11 pages:488-503 https://dx.doi.org/10.1007/s12325-021-01921-5 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 39 2021 1 17 11 488-503 |
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10.1007/s12325-021-01921-5 doi (DE-627)SPR046085459 (SPR)s12325-021-01921-5-e DE-627 ger DE-627 rakwb eng Xu, Junyu verfasserin aut Pharmacokinetics, Pharmacodynamics, and Safety of Dulaglutide After Single or Multiple Doses in Chinese Healthy Subjects and Patients with T2DM: A Randomized, Placebo-Controlled, Phase I Study 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature 2021 Introduction This study evaluated the pharmacokinetics, pharmacodynamics, and safety of a single dulaglutide dose in Chinese healthy subjects and of multiple dulaglutide doses in Chinese patients with type 2 diabetes mellitus (T2DM). Methods This two-part, double-blind, placebo-controlled study included 16 healthy subjects randomized to receive a single dose of placebo and two of three dulaglutide doses (0.5 mg, 0.75 mg, or 1.5 mg) in three treatment periods, and 42 patients with T2DM randomized to receive placebo or one of the three dulaglutide doses once weekly for 4 weeks. Pharmacokinetics and safety parameters were assessed in all participants, and pharmacodynamics effects were investigated in patients with T2DM. Results Following a single-dose administration of 0.5 mg, 0.75 mg, or 1.5 mg dulaglutide in healthy subjects, geometric mean maximum concentrations (Cmax) were 29.4, 44.2, and 81.5 ng/mL, respectively. Following weekly administration in patients with T2DM for 4 weeks, Cmax were 26.3, 41.4, and 70.2 ng/mL, respectively, with accumulation ratios of 1.33–1.39. Geometric mean for half-life of 4–5 days and median time to Cmax (tmax) of approximately 48 h were observed in both study populations. Dose-proportional increases in drug exposure were observed after both single and multiple dosing. Significant reductions in baseline-corrected fasting glucose and hemoglobin A1c (HbA1c) were observed in patients with T2DM who received dulaglutide 0.75 mg and 1.5 mg. Dulaglutide was well tolerated, with the majority of adverse events being gastrointestinal disorders of mild severity. Conclusions Pharmacokinetics, pharmacodynamics, and safety profiles of dulaglutide demonstrated in the present study support a once-weekly dosing regimen in Chinese patients with T2DM. Trial Registration NCT01667900 (ClinicalTrials.gov). Dulaglutide (dpeaa)DE-He213 Phase I study (dpeaa)DE-He213 Chinese participants (dpeaa)DE-He213 Zhang, Yifei aut Li, Yiming aut Zhao, Xia aut Zhou, Weiwei aut Loghin, Corina aut Tham, Lai San aut Cui, Xuewei aut Cui, Yimin (orcid)0000-0002-4186-1005 aut Wang, Weiqing aut Enthalten in Advances in therapy Tarporley : Springer Healthcare Communications, 2000 39(2021), 1 vom: 17. Nov., Seite 488-503 (DE-627)563170433 (DE-600)2421646-X 1865-8652 nnns volume:39 year:2021 number:1 day:17 month:11 pages:488-503 https://dx.doi.org/10.1007/s12325-021-01921-5 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 39 2021 1 17 11 488-503 |
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10.1007/s12325-021-01921-5 doi (DE-627)SPR046085459 (SPR)s12325-021-01921-5-e DE-627 ger DE-627 rakwb eng Xu, Junyu verfasserin aut Pharmacokinetics, Pharmacodynamics, and Safety of Dulaglutide After Single or Multiple Doses in Chinese Healthy Subjects and Patients with T2DM: A Randomized, Placebo-Controlled, Phase I Study 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature 2021 Introduction This study evaluated the pharmacokinetics, pharmacodynamics, and safety of a single dulaglutide dose in Chinese healthy subjects and of multiple dulaglutide doses in Chinese patients with type 2 diabetes mellitus (T2DM). Methods This two-part, double-blind, placebo-controlled study included 16 healthy subjects randomized to receive a single dose of placebo and two of three dulaglutide doses (0.5 mg, 0.75 mg, or 1.5 mg) in three treatment periods, and 42 patients with T2DM randomized to receive placebo or one of the three dulaglutide doses once weekly for 4 weeks. Pharmacokinetics and safety parameters were assessed in all participants, and pharmacodynamics effects were investigated in patients with T2DM. Results Following a single-dose administration of 0.5 mg, 0.75 mg, or 1.5 mg dulaglutide in healthy subjects, geometric mean maximum concentrations (Cmax) were 29.4, 44.2, and 81.5 ng/mL, respectively. Following weekly administration in patients with T2DM for 4 weeks, Cmax were 26.3, 41.4, and 70.2 ng/mL, respectively, with accumulation ratios of 1.33–1.39. Geometric mean for half-life of 4–5 days and median time to Cmax (tmax) of approximately 48 h were observed in both study populations. Dose-proportional increases in drug exposure were observed after both single and multiple dosing. Significant reductions in baseline-corrected fasting glucose and hemoglobin A1c (HbA1c) were observed in patients with T2DM who received dulaglutide 0.75 mg and 1.5 mg. Dulaglutide was well tolerated, with the majority of adverse events being gastrointestinal disorders of mild severity. Conclusions Pharmacokinetics, pharmacodynamics, and safety profiles of dulaglutide demonstrated in the present study support a once-weekly dosing regimen in Chinese patients with T2DM. Trial Registration NCT01667900 (ClinicalTrials.gov). Dulaglutide (dpeaa)DE-He213 Phase I study (dpeaa)DE-He213 Chinese participants (dpeaa)DE-He213 Zhang, Yifei aut Li, Yiming aut Zhao, Xia aut Zhou, Weiwei aut Loghin, Corina aut Tham, Lai San aut Cui, Xuewei aut Cui, Yimin (orcid)0000-0002-4186-1005 aut Wang, Weiqing aut Enthalten in Advances in therapy Tarporley : Springer Healthcare Communications, 2000 39(2021), 1 vom: 17. Nov., Seite 488-503 (DE-627)563170433 (DE-600)2421646-X 1865-8652 nnns volume:39 year:2021 number:1 day:17 month:11 pages:488-503 https://dx.doi.org/10.1007/s12325-021-01921-5 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 39 2021 1 17 11 488-503 |
allfieldsGer |
10.1007/s12325-021-01921-5 doi (DE-627)SPR046085459 (SPR)s12325-021-01921-5-e DE-627 ger DE-627 rakwb eng Xu, Junyu verfasserin aut Pharmacokinetics, Pharmacodynamics, and Safety of Dulaglutide After Single or Multiple Doses in Chinese Healthy Subjects and Patients with T2DM: A Randomized, Placebo-Controlled, Phase I Study 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature 2021 Introduction This study evaluated the pharmacokinetics, pharmacodynamics, and safety of a single dulaglutide dose in Chinese healthy subjects and of multiple dulaglutide doses in Chinese patients with type 2 diabetes mellitus (T2DM). Methods This two-part, double-blind, placebo-controlled study included 16 healthy subjects randomized to receive a single dose of placebo and two of three dulaglutide doses (0.5 mg, 0.75 mg, or 1.5 mg) in three treatment periods, and 42 patients with T2DM randomized to receive placebo or one of the three dulaglutide doses once weekly for 4 weeks. Pharmacokinetics and safety parameters were assessed in all participants, and pharmacodynamics effects were investigated in patients with T2DM. Results Following a single-dose administration of 0.5 mg, 0.75 mg, or 1.5 mg dulaglutide in healthy subjects, geometric mean maximum concentrations (Cmax) were 29.4, 44.2, and 81.5 ng/mL, respectively. Following weekly administration in patients with T2DM for 4 weeks, Cmax were 26.3, 41.4, and 70.2 ng/mL, respectively, with accumulation ratios of 1.33–1.39. Geometric mean for half-life of 4–5 days and median time to Cmax (tmax) of approximately 48 h were observed in both study populations. Dose-proportional increases in drug exposure were observed after both single and multiple dosing. Significant reductions in baseline-corrected fasting glucose and hemoglobin A1c (HbA1c) were observed in patients with T2DM who received dulaglutide 0.75 mg and 1.5 mg. Dulaglutide was well tolerated, with the majority of adverse events being gastrointestinal disorders of mild severity. Conclusions Pharmacokinetics, pharmacodynamics, and safety profiles of dulaglutide demonstrated in the present study support a once-weekly dosing regimen in Chinese patients with T2DM. Trial Registration NCT01667900 (ClinicalTrials.gov). Dulaglutide (dpeaa)DE-He213 Phase I study (dpeaa)DE-He213 Chinese participants (dpeaa)DE-He213 Zhang, Yifei aut Li, Yiming aut Zhao, Xia aut Zhou, Weiwei aut Loghin, Corina aut Tham, Lai San aut Cui, Xuewei aut Cui, Yimin (orcid)0000-0002-4186-1005 aut Wang, Weiqing aut Enthalten in Advances in therapy Tarporley : Springer Healthcare Communications, 2000 39(2021), 1 vom: 17. Nov., Seite 488-503 (DE-627)563170433 (DE-600)2421646-X 1865-8652 nnns volume:39 year:2021 number:1 day:17 month:11 pages:488-503 https://dx.doi.org/10.1007/s12325-021-01921-5 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 39 2021 1 17 11 488-503 |
allfieldsSound |
10.1007/s12325-021-01921-5 doi (DE-627)SPR046085459 (SPR)s12325-021-01921-5-e DE-627 ger DE-627 rakwb eng Xu, Junyu verfasserin aut Pharmacokinetics, Pharmacodynamics, and Safety of Dulaglutide After Single or Multiple Doses in Chinese Healthy Subjects and Patients with T2DM: A Randomized, Placebo-Controlled, Phase I Study 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature 2021 Introduction This study evaluated the pharmacokinetics, pharmacodynamics, and safety of a single dulaglutide dose in Chinese healthy subjects and of multiple dulaglutide doses in Chinese patients with type 2 diabetes mellitus (T2DM). Methods This two-part, double-blind, placebo-controlled study included 16 healthy subjects randomized to receive a single dose of placebo and two of three dulaglutide doses (0.5 mg, 0.75 mg, or 1.5 mg) in three treatment periods, and 42 patients with T2DM randomized to receive placebo or one of the three dulaglutide doses once weekly for 4 weeks. Pharmacokinetics and safety parameters were assessed in all participants, and pharmacodynamics effects were investigated in patients with T2DM. Results Following a single-dose administration of 0.5 mg, 0.75 mg, or 1.5 mg dulaglutide in healthy subjects, geometric mean maximum concentrations (Cmax) were 29.4, 44.2, and 81.5 ng/mL, respectively. Following weekly administration in patients with T2DM for 4 weeks, Cmax were 26.3, 41.4, and 70.2 ng/mL, respectively, with accumulation ratios of 1.33–1.39. Geometric mean for half-life of 4–5 days and median time to Cmax (tmax) of approximately 48 h were observed in both study populations. Dose-proportional increases in drug exposure were observed after both single and multiple dosing. Significant reductions in baseline-corrected fasting glucose and hemoglobin A1c (HbA1c) were observed in patients with T2DM who received dulaglutide 0.75 mg and 1.5 mg. Dulaglutide was well tolerated, with the majority of adverse events being gastrointestinal disorders of mild severity. Conclusions Pharmacokinetics, pharmacodynamics, and safety profiles of dulaglutide demonstrated in the present study support a once-weekly dosing regimen in Chinese patients with T2DM. Trial Registration NCT01667900 (ClinicalTrials.gov). Dulaglutide (dpeaa)DE-He213 Phase I study (dpeaa)DE-He213 Chinese participants (dpeaa)DE-He213 Zhang, Yifei aut Li, Yiming aut Zhao, Xia aut Zhou, Weiwei aut Loghin, Corina aut Tham, Lai San aut Cui, Xuewei aut Cui, Yimin (orcid)0000-0002-4186-1005 aut Wang, Weiqing aut Enthalten in Advances in therapy Tarporley : Springer Healthcare Communications, 2000 39(2021), 1 vom: 17. Nov., Seite 488-503 (DE-627)563170433 (DE-600)2421646-X 1865-8652 nnns volume:39 year:2021 number:1 day:17 month:11 pages:488-503 https://dx.doi.org/10.1007/s12325-021-01921-5 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 39 2021 1 17 11 488-503 |
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Xu, Junyu @@aut@@ Zhang, Yifei @@aut@@ Li, Yiming @@aut@@ Zhao, Xia @@aut@@ Zhou, Weiwei @@aut@@ Loghin, Corina @@aut@@ Tham, Lai San @@aut@@ Cui, Xuewei @@aut@@ Cui, Yimin @@aut@@ Wang, Weiqing @@aut@@ |
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Methods This two-part, double-blind, placebo-controlled study included 16 healthy subjects randomized to receive a single dose of placebo and two of three dulaglutide doses (0.5 mg, 0.75 mg, or 1.5 mg) in three treatment periods, and 42 patients with T2DM randomized to receive placebo or one of the three dulaglutide doses once weekly for 4 weeks. Pharmacokinetics and safety parameters were assessed in all participants, and pharmacodynamics effects were investigated in patients with T2DM. Results Following a single-dose administration of 0.5 mg, 0.75 mg, or 1.5 mg dulaglutide in healthy subjects, geometric mean maximum concentrations (Cmax) were 29.4, 44.2, and 81.5 ng/mL, respectively. Following weekly administration in patients with T2DM for 4 weeks, Cmax were 26.3, 41.4, and 70.2 ng/mL, respectively, with accumulation ratios of 1.33–1.39. Geometric mean for half-life of 4–5 days and median time to Cmax (tmax) of approximately 48 h were observed in both study populations. Dose-proportional increases in drug exposure were observed after both single and multiple dosing. Significant reductions in baseline-corrected fasting glucose and hemoglobin A1c (HbA1c) were observed in patients with T2DM who received dulaglutide 0.75 mg and 1.5 mg. Dulaglutide was well tolerated, with the majority of adverse events being gastrointestinal disorders of mild severity. Conclusions Pharmacokinetics, pharmacodynamics, and safety profiles of dulaglutide demonstrated in the present study support a once-weekly dosing regimen in Chinese patients with T2DM. 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Xu, Junyu misc Dulaglutide misc Phase I study misc Chinese participants Pharmacokinetics, Pharmacodynamics, and Safety of Dulaglutide After Single or Multiple Doses in Chinese Healthy Subjects and Patients with T2DM: A Randomized, Placebo-Controlled, Phase I Study |
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Pharmacokinetics, Pharmacodynamics, and Safety of Dulaglutide After Single or Multiple Doses in Chinese Healthy Subjects and Patients with T2DM: A Randomized, Placebo-Controlled, Phase I Study Dulaglutide (dpeaa)DE-He213 Phase I study (dpeaa)DE-He213 Chinese participants (dpeaa)DE-He213 |
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Pharmacokinetics, Pharmacodynamics, and Safety of Dulaglutide After Single or Multiple Doses in Chinese Healthy Subjects and Patients with T2DM: A Randomized, Placebo-Controlled, Phase I Study |
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Pharmacokinetics, Pharmacodynamics, and Safety of Dulaglutide After Single or Multiple Doses in Chinese Healthy Subjects and Patients with T2DM: A Randomized, Placebo-Controlled, Phase I Study |
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Xu, Junyu Zhang, Yifei Li, Yiming Zhao, Xia Zhou, Weiwei Loghin, Corina Tham, Lai San Cui, Xuewei Cui, Yimin Wang, Weiqing |
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pharmacokinetics, pharmacodynamics, and safety of dulaglutide after single or multiple doses in chinese healthy subjects and patients with t2dm: a randomized, placebo-controlled, phase i study |
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Pharmacokinetics, Pharmacodynamics, and Safety of Dulaglutide After Single or Multiple Doses in Chinese Healthy Subjects and Patients with T2DM: A Randomized, Placebo-Controlled, Phase I Study |
abstract |
Introduction This study evaluated the pharmacokinetics, pharmacodynamics, and safety of a single dulaglutide dose in Chinese healthy subjects and of multiple dulaglutide doses in Chinese patients with type 2 diabetes mellitus (T2DM). Methods This two-part, double-blind, placebo-controlled study included 16 healthy subjects randomized to receive a single dose of placebo and two of three dulaglutide doses (0.5 mg, 0.75 mg, or 1.5 mg) in three treatment periods, and 42 patients with T2DM randomized to receive placebo or one of the three dulaglutide doses once weekly for 4 weeks. Pharmacokinetics and safety parameters were assessed in all participants, and pharmacodynamics effects were investigated in patients with T2DM. Results Following a single-dose administration of 0.5 mg, 0.75 mg, or 1.5 mg dulaglutide in healthy subjects, geometric mean maximum concentrations (Cmax) were 29.4, 44.2, and 81.5 ng/mL, respectively. Following weekly administration in patients with T2DM for 4 weeks, Cmax were 26.3, 41.4, and 70.2 ng/mL, respectively, with accumulation ratios of 1.33–1.39. Geometric mean for half-life of 4–5 days and median time to Cmax (tmax) of approximately 48 h were observed in both study populations. Dose-proportional increases in drug exposure were observed after both single and multiple dosing. Significant reductions in baseline-corrected fasting glucose and hemoglobin A1c (HbA1c) were observed in patients with T2DM who received dulaglutide 0.75 mg and 1.5 mg. Dulaglutide was well tolerated, with the majority of adverse events being gastrointestinal disorders of mild severity. Conclusions Pharmacokinetics, pharmacodynamics, and safety profiles of dulaglutide demonstrated in the present study support a once-weekly dosing regimen in Chinese patients with T2DM. Trial Registration NCT01667900 (ClinicalTrials.gov). © The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature 2021 |
abstractGer |
Introduction This study evaluated the pharmacokinetics, pharmacodynamics, and safety of a single dulaglutide dose in Chinese healthy subjects and of multiple dulaglutide doses in Chinese patients with type 2 diabetes mellitus (T2DM). Methods This two-part, double-blind, placebo-controlled study included 16 healthy subjects randomized to receive a single dose of placebo and two of three dulaglutide doses (0.5 mg, 0.75 mg, or 1.5 mg) in three treatment periods, and 42 patients with T2DM randomized to receive placebo or one of the three dulaglutide doses once weekly for 4 weeks. Pharmacokinetics and safety parameters were assessed in all participants, and pharmacodynamics effects were investigated in patients with T2DM. Results Following a single-dose administration of 0.5 mg, 0.75 mg, or 1.5 mg dulaglutide in healthy subjects, geometric mean maximum concentrations (Cmax) were 29.4, 44.2, and 81.5 ng/mL, respectively. Following weekly administration in patients with T2DM for 4 weeks, Cmax were 26.3, 41.4, and 70.2 ng/mL, respectively, with accumulation ratios of 1.33–1.39. Geometric mean for half-life of 4–5 days and median time to Cmax (tmax) of approximately 48 h were observed in both study populations. Dose-proportional increases in drug exposure were observed after both single and multiple dosing. Significant reductions in baseline-corrected fasting glucose and hemoglobin A1c (HbA1c) were observed in patients with T2DM who received dulaglutide 0.75 mg and 1.5 mg. Dulaglutide was well tolerated, with the majority of adverse events being gastrointestinal disorders of mild severity. Conclusions Pharmacokinetics, pharmacodynamics, and safety profiles of dulaglutide demonstrated in the present study support a once-weekly dosing regimen in Chinese patients with T2DM. Trial Registration NCT01667900 (ClinicalTrials.gov). © The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature 2021 |
abstract_unstemmed |
Introduction This study evaluated the pharmacokinetics, pharmacodynamics, and safety of a single dulaglutide dose in Chinese healthy subjects and of multiple dulaglutide doses in Chinese patients with type 2 diabetes mellitus (T2DM). Methods This two-part, double-blind, placebo-controlled study included 16 healthy subjects randomized to receive a single dose of placebo and two of three dulaglutide doses (0.5 mg, 0.75 mg, or 1.5 mg) in three treatment periods, and 42 patients with T2DM randomized to receive placebo or one of the three dulaglutide doses once weekly for 4 weeks. Pharmacokinetics and safety parameters were assessed in all participants, and pharmacodynamics effects were investigated in patients with T2DM. Results Following a single-dose administration of 0.5 mg, 0.75 mg, or 1.5 mg dulaglutide in healthy subjects, geometric mean maximum concentrations (Cmax) were 29.4, 44.2, and 81.5 ng/mL, respectively. Following weekly administration in patients with T2DM for 4 weeks, Cmax were 26.3, 41.4, and 70.2 ng/mL, respectively, with accumulation ratios of 1.33–1.39. Geometric mean for half-life of 4–5 days and median time to Cmax (tmax) of approximately 48 h were observed in both study populations. Dose-proportional increases in drug exposure were observed after both single and multiple dosing. Significant reductions in baseline-corrected fasting glucose and hemoglobin A1c (HbA1c) were observed in patients with T2DM who received dulaglutide 0.75 mg and 1.5 mg. Dulaglutide was well tolerated, with the majority of adverse events being gastrointestinal disorders of mild severity. Conclusions Pharmacokinetics, pharmacodynamics, and safety profiles of dulaglutide demonstrated in the present study support a once-weekly dosing regimen in Chinese patients with T2DM. Trial Registration NCT01667900 (ClinicalTrials.gov). © The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature 2021 |
collection_details |
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title_short |
Pharmacokinetics, Pharmacodynamics, and Safety of Dulaglutide After Single or Multiple Doses in Chinese Healthy Subjects and Patients with T2DM: A Randomized, Placebo-Controlled, Phase I Study |
url |
https://dx.doi.org/10.1007/s12325-021-01921-5 |
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Zhang, Yifei Li, Yiming Zhao, Xia Zhou, Weiwei Loghin, Corina Tham, Lai San Cui, Xuewei Cui, Yimin Wang, Weiqing |
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Zhang, Yifei Li, Yiming Zhao, Xia Zhou, Weiwei Loghin, Corina Tham, Lai San Cui, Xuewei Cui, Yimin Wang, Weiqing |
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10.1007/s12325-021-01921-5 |
up_date |
2024-07-03T20:15:56.135Z |
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score |
7.399805 |