A Phase 1, Multicenter, Open-Label Study to Evaluate the Pharmacokinetics of Iberdomide in Subjects with Mild, Moderate, or Severe Hepatic Impairment Compared with Healthy Subjects
Yiming Cheng,1 Ying Ye,1 Allison Gaudy,1 Atalanta Ghosh,2 Yongjun Xue,3 Alice Wang,1 Simon Zhou,1 Yan Li1 1Clinical Pharmacology & Pharmacometrics, Bristol Myers Squibb, Princeton, NJ, USA; 2Global Biometrics and Data Sciences, Bristol Myers Squibb, Princeton, NJ, USA; 3Nonclinical Research &...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Dove Medical Press
2023-02-01
|
| Series: | Clinical Pharmacology: Advances and Applications |
| Subjects: | |
| Online Access: | https://www.dovepress.com/a-phase-1-multicenter-open-label-study-to-evaluate-the-pharmacokinetic-peer-reviewed-fulltext-article-CPAA |
| _version_ | 1811162869198225408 |
|---|---|
| author | Cheng Y Ye Y Gaudy A Ghosh A Xue Y Wang A Zhou S Li Y |
| author_facet | Cheng Y Ye Y Gaudy A Ghosh A Xue Y Wang A Zhou S Li Y |
| author_sort | Cheng Y |
| collection | DOAJ |
| description | Yiming Cheng,1 Ying Ye,1 Allison Gaudy,1 Atalanta Ghosh,2 Yongjun Xue,3 Alice Wang,1 Simon Zhou,1 Yan Li1 1Clinical Pharmacology & Pharmacometrics, Bristol Myers Squibb, Princeton, NJ, USA; 2Global Biometrics and Data Sciences, Bristol Myers Squibb, Princeton, NJ, USA; 3Nonclinical Research & Development, Bristol Myers Squibb, Princeton, NJ, USACorrespondence: Yan Li, Clinical Pharmacology & Pharmacometrics, Bristol Myers Squibb, 556 Morris Ave, Summit, Princeton, NJ, 07901, USA, Tel +1 908-481-6203, Email Yan.Li@bms.comIntroduction: Iberdomide, a novel cereblon modulator (CELMoD®), is currently under clinical investigation for hematology indications. To evaluate the influence of hepatic impairment on the pharmacokinetics (PK) of iberdomide and its major active metabolite M12, a phase 1, multicenter, open-label study was conducted in healthy subjects and subjects with mild, moderate, and severe hepatic impairment.Methods: Forty subjects were enrolled in the study and divided into five groups based on hepatic function. 1 mg iberdomide was administered and plasma samples were collected to evaluate the pharmacokinetics of iberdomide and M12.Results: After a single dose of iberdomide (1 mg), mean iberdomide Cmax (maximum observed concentration) and AUC (area under the concentration-time curve) exposure were generally comparable between hepatic impairment (HI) subjects (severe, moderate and mild) and their respective matched normal controls. Mean Cmax and AUC exposure of the metabolite M12 were generally comparable between mild HI and matched normal subjects. However, mean Cmax of the M12 was 30% and 65% lower and AUC was 57% and 63% lower in moderate and severe HI subjects as compared to their respective matched normal controls. However, given the relatively low M12 exposure as compared to its parent drug, the observed differences were not considered clinically meaningful.Conclusion: In summary, 1 mg single oral dose of iberdomide was generally well-tolerated. HI (mild, moderate or severe) had no clinically relevant impact on iberdomide PK and therefore, no dose adjustment is warranted.Keywords: hepatic impairment, iberdomide, pharmacokinetics |
| first_indexed | 2024-04-10T06:37:18Z |
| format | Article |
| id | doaj.art-5cd3f02d399d417c8102ca8bd64a478d |
| institution | Directory Open Access Journal |
| issn | 1179-1438 |
| language | English |
| last_indexed | 2024-04-10T06:37:18Z |
| publishDate | 2023-02-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Clinical Pharmacology: Advances and Applications |
| spelling | doaj.art-5cd3f02d399d417c8102ca8bd64a478d2023-02-28T18:02:44ZengDove Medical PressClinical Pharmacology: Advances and Applications1179-14382023-02-01Volume 1591981933A Phase 1, Multicenter, Open-Label Study to Evaluate the Pharmacokinetics of Iberdomide in Subjects with Mild, Moderate, or Severe Hepatic Impairment Compared with Healthy SubjectsCheng YYe YGaudy AGhosh AXue YWang AZhou SLi YYiming Cheng,1 Ying Ye,1 Allison Gaudy,1 Atalanta Ghosh,2 Yongjun Xue,3 Alice Wang,1 Simon Zhou,1 Yan Li1 1Clinical Pharmacology & Pharmacometrics, Bristol Myers Squibb, Princeton, NJ, USA; 2Global Biometrics and Data Sciences, Bristol Myers Squibb, Princeton, NJ, USA; 3Nonclinical Research & Development, Bristol Myers Squibb, Princeton, NJ, USACorrespondence: Yan Li, Clinical Pharmacology & Pharmacometrics, Bristol Myers Squibb, 556 Morris Ave, Summit, Princeton, NJ, 07901, USA, Tel +1 908-481-6203, Email Yan.Li@bms.comIntroduction: Iberdomide, a novel cereblon modulator (CELMoD®), is currently under clinical investigation for hematology indications. To evaluate the influence of hepatic impairment on the pharmacokinetics (PK) of iberdomide and its major active metabolite M12, a phase 1, multicenter, open-label study was conducted in healthy subjects and subjects with mild, moderate, and severe hepatic impairment.Methods: Forty subjects were enrolled in the study and divided into five groups based on hepatic function. 1 mg iberdomide was administered and plasma samples were collected to evaluate the pharmacokinetics of iberdomide and M12.Results: After a single dose of iberdomide (1 mg), mean iberdomide Cmax (maximum observed concentration) and AUC (area under the concentration-time curve) exposure were generally comparable between hepatic impairment (HI) subjects (severe, moderate and mild) and their respective matched normal controls. Mean Cmax and AUC exposure of the metabolite M12 were generally comparable between mild HI and matched normal subjects. However, mean Cmax of the M12 was 30% and 65% lower and AUC was 57% and 63% lower in moderate and severe HI subjects as compared to their respective matched normal controls. However, given the relatively low M12 exposure as compared to its parent drug, the observed differences were not considered clinically meaningful.Conclusion: In summary, 1 mg single oral dose of iberdomide was generally well-tolerated. HI (mild, moderate or severe) had no clinically relevant impact on iberdomide PK and therefore, no dose adjustment is warranted.Keywords: hepatic impairment, iberdomide, pharmacokineticshttps://www.dovepress.com/a-phase-1-multicenter-open-label-study-to-evaluate-the-pharmacokinetic-peer-reviewed-fulltext-article-CPAAhepatic impairmentiberdomidepharmacokinetics |
| spellingShingle | Cheng Y Ye Y Gaudy A Ghosh A Xue Y Wang A Zhou S Li Y A Phase 1, Multicenter, Open-Label Study to Evaluate the Pharmacokinetics of Iberdomide in Subjects with Mild, Moderate, or Severe Hepatic Impairment Compared with Healthy Subjects Clinical Pharmacology: Advances and Applications hepatic impairment iberdomide pharmacokinetics |
| title | A Phase 1, Multicenter, Open-Label Study to Evaluate the Pharmacokinetics of Iberdomide in Subjects with Mild, Moderate, or Severe Hepatic Impairment Compared with Healthy Subjects |
| title_full | A Phase 1, Multicenter, Open-Label Study to Evaluate the Pharmacokinetics of Iberdomide in Subjects with Mild, Moderate, or Severe Hepatic Impairment Compared with Healthy Subjects |
| title_fullStr | A Phase 1, Multicenter, Open-Label Study to Evaluate the Pharmacokinetics of Iberdomide in Subjects with Mild, Moderate, or Severe Hepatic Impairment Compared with Healthy Subjects |
| title_full_unstemmed | A Phase 1, Multicenter, Open-Label Study to Evaluate the Pharmacokinetics of Iberdomide in Subjects with Mild, Moderate, or Severe Hepatic Impairment Compared with Healthy Subjects |
| title_short | A Phase 1, Multicenter, Open-Label Study to Evaluate the Pharmacokinetics of Iberdomide in Subjects with Mild, Moderate, or Severe Hepatic Impairment Compared with Healthy Subjects |
| title_sort | phase 1 multicenter open label study to evaluate the pharmacokinetics of iberdomide in subjects with mild moderate or severe hepatic impairment compared with healthy subjects |
| topic | hepatic impairment iberdomide pharmacokinetics |
| url | https://www.dovepress.com/a-phase-1-multicenter-open-label-study-to-evaluate-the-pharmacokinetic-peer-reviewed-fulltext-article-CPAA |
| work_keys_str_mv | AT chengy aphase1multicenteropenlabelstudytoevaluatethepharmacokineticsofiberdomideinsubjectswithmildmoderateorseverehepaticimpairmentcomparedwithhealthysubjects AT yey aphase1multicenteropenlabelstudytoevaluatethepharmacokineticsofiberdomideinsubjectswithmildmoderateorseverehepaticimpairmentcomparedwithhealthysubjects AT gaudya aphase1multicenteropenlabelstudytoevaluatethepharmacokineticsofiberdomideinsubjectswithmildmoderateorseverehepaticimpairmentcomparedwithhealthysubjects AT ghosha aphase1multicenteropenlabelstudytoevaluatethepharmacokineticsofiberdomideinsubjectswithmildmoderateorseverehepaticimpairmentcomparedwithhealthysubjects AT xuey aphase1multicenteropenlabelstudytoevaluatethepharmacokineticsofiberdomideinsubjectswithmildmoderateorseverehepaticimpairmentcomparedwithhealthysubjects AT wanga aphase1multicenteropenlabelstudytoevaluatethepharmacokineticsofiberdomideinsubjectswithmildmoderateorseverehepaticimpairmentcomparedwithhealthysubjects AT zhous aphase1multicenteropenlabelstudytoevaluatethepharmacokineticsofiberdomideinsubjectswithmildmoderateorseverehepaticimpairmentcomparedwithhealthysubjects AT liy aphase1multicenteropenlabelstudytoevaluatethepharmacokineticsofiberdomideinsubjectswithmildmoderateorseverehepaticimpairmentcomparedwithhealthysubjects AT chengy phase1multicenteropenlabelstudytoevaluatethepharmacokineticsofiberdomideinsubjectswithmildmoderateorseverehepaticimpairmentcomparedwithhealthysubjects AT yey phase1multicenteropenlabelstudytoevaluatethepharmacokineticsofiberdomideinsubjectswithmildmoderateorseverehepaticimpairmentcomparedwithhealthysubjects AT gaudya phase1multicenteropenlabelstudytoevaluatethepharmacokineticsofiberdomideinsubjectswithmildmoderateorseverehepaticimpairmentcomparedwithhealthysubjects AT ghosha phase1multicenteropenlabelstudytoevaluatethepharmacokineticsofiberdomideinsubjectswithmildmoderateorseverehepaticimpairmentcomparedwithhealthysubjects AT xuey phase1multicenteropenlabelstudytoevaluatethepharmacokineticsofiberdomideinsubjectswithmildmoderateorseverehepaticimpairmentcomparedwithhealthysubjects AT wanga phase1multicenteropenlabelstudytoevaluatethepharmacokineticsofiberdomideinsubjectswithmildmoderateorseverehepaticimpairmentcomparedwithhealthysubjects AT zhous phase1multicenteropenlabelstudytoevaluatethepharmacokineticsofiberdomideinsubjectswithmildmoderateorseverehepaticimpairmentcomparedwithhealthysubjects AT liy phase1multicenteropenlabelstudytoevaluatethepharmacokineticsofiberdomideinsubjectswithmildmoderateorseverehepaticimpairmentcomparedwithhealthysubjects |