Pharmacokinetics of Bocidelpar, ASP0367, in Renal and Hepatic Impairment: Results From Two Phase 1 Studies
ABSTRACT Bocidelpar is a peroxisome proliferator‐activated receptor δ modulator designed to address mitochondrial impairment. Two open‐label, single‐dose phase 1 studies (NCT05117294/NCT04942964) investigated the effect of severe renal or mild/moderate hepatic impairment on bocidelpar pharmacokineti...
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Wiley
2025-08-01
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| Series: | Clinical and Translational Science |
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| Online Access: | https://doi.org/10.1111/cts.70310 |
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| author | Megumi Iwai Nakyo Heo Kentaro Hashimoto Sayuri Guro Selina Moy Anna Spence Tomasz Wojtkowski Lauren Benner Melanie Helmick Tong Zhu Brian C. Ferslew |
| author_facet | Megumi Iwai Nakyo Heo Kentaro Hashimoto Sayuri Guro Selina Moy Anna Spence Tomasz Wojtkowski Lauren Benner Melanie Helmick Tong Zhu Brian C. Ferslew |
| author_sort | Megumi Iwai |
| collection | DOAJ |
| description | ABSTRACT Bocidelpar is a peroxisome proliferator‐activated receptor δ modulator designed to address mitochondrial impairment. Two open‐label, single‐dose phase 1 studies (NCT05117294/NCT04942964) investigated the effect of severe renal or mild/moderate hepatic impairment on bocidelpar pharmacokinetics and safety. Adult participants received 75 mg bocidelpar and underwent serial blood and urine sampling over 4 days to evaluate the pharmacokinetics of bocidelpar. Thirteen participants were included in the renal cohort (severe impairment, n = 7; healthy participants, n = 6). A minimal increase was observed in the maximum concentration (Cmax) of the severe impairment group versus healthy participants (geometric least squares mean [GeoLSM] ratio [90% CI], 139.66% [86.33, 225.92]). No clear changes were observed in the area under the curve (AUC). Twenty‐five participants were included in the hepatic cohort (mild impairment, n = 8; moderate impairment, n = 8; healthy participants, n = 9). Compared with matched controls, increased Cmax was observed in the mild (GeoLSM ratio [90% CI], 181.37% [95.47, 344.56]) and moderate (GeoLSM ratio [90% CI], 298.78% [145.00, 615.65]) impairment groups. Mild impairment did not substantially affect the AUCinf versus matched controls (GeoLSM ratio [90% CI], 110.73% [82.16, 149.24]); however, it was higher in the moderate impairment group versus matched controls (GeoLSM ratio [90% CI], 195.58% [115.26, 331.88]). Across both studies, five treatment‐emergent adverse events were observed in five participants; all were considered mild in severity. Overall, bocidelpar was well tolerated and had an acceptable safety profile. Severe renal impairment had a minimal effect on bocidelpar pharmacokinetics, while moderate hepatic impairment resulted in increased bocidelpar concentration and exposure compared with matched controls. |
| format | Article |
| id | doaj-art-31209ec3697545cd92c64849d6c8b67d |
| institution | Kabale University |
| issn | 1752-8054 1752-8062 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Wiley |
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| series | Clinical and Translational Science |
| spelling | doaj-art-31209ec3697545cd92c64849d6c8b67d2025-08-23T17:10:42ZengWileyClinical and Translational Science1752-80541752-80622025-08-01188n/an/a10.1111/cts.70310Pharmacokinetics of Bocidelpar, ASP0367, in Renal and Hepatic Impairment: Results From Two Phase 1 StudiesMegumi Iwai0Nakyo Heo1Kentaro Hashimoto2Sayuri Guro3Selina Moy4Anna Spence5Tomasz Wojtkowski6Lauren Benner7Melanie Helmick8Tong Zhu9Brian C. Ferslew10Astellas Pharma Inc. Tokyo JapanAstellas Pharma Inc. Northbrook Illinois USAAstellas Pharma Inc. Tokyo JapanAstellas Pharma Inc. Tokyo JapanAstellas Pharma Inc. Northbrook Illinois USAAstellas Pharma Inc. Northbrook Illinois USAAstellas Pharma Inc. Northbrook Illinois USAAstellas Pharma Inc. Northbrook Illinois USAAstellas Pharma Inc. Northbrook Illinois USAAstellas Pharma Inc. Northbrook Illinois USAAstellas Pharma Inc. Northbrook Illinois USAABSTRACT Bocidelpar is a peroxisome proliferator‐activated receptor δ modulator designed to address mitochondrial impairment. Two open‐label, single‐dose phase 1 studies (NCT05117294/NCT04942964) investigated the effect of severe renal or mild/moderate hepatic impairment on bocidelpar pharmacokinetics and safety. Adult participants received 75 mg bocidelpar and underwent serial blood and urine sampling over 4 days to evaluate the pharmacokinetics of bocidelpar. Thirteen participants were included in the renal cohort (severe impairment, n = 7; healthy participants, n = 6). A minimal increase was observed in the maximum concentration (Cmax) of the severe impairment group versus healthy participants (geometric least squares mean [GeoLSM] ratio [90% CI], 139.66% [86.33, 225.92]). No clear changes were observed in the area under the curve (AUC). Twenty‐five participants were included in the hepatic cohort (mild impairment, n = 8; moderate impairment, n = 8; healthy participants, n = 9). Compared with matched controls, increased Cmax was observed in the mild (GeoLSM ratio [90% CI], 181.37% [95.47, 344.56]) and moderate (GeoLSM ratio [90% CI], 298.78% [145.00, 615.65]) impairment groups. Mild impairment did not substantially affect the AUCinf versus matched controls (GeoLSM ratio [90% CI], 110.73% [82.16, 149.24]); however, it was higher in the moderate impairment group versus matched controls (GeoLSM ratio [90% CI], 195.58% [115.26, 331.88]). Across both studies, five treatment‐emergent adverse events were observed in five participants; all were considered mild in severity. Overall, bocidelpar was well tolerated and had an acceptable safety profile. Severe renal impairment had a minimal effect on bocidelpar pharmacokinetics, while moderate hepatic impairment resulted in increased bocidelpar concentration and exposure compared with matched controls.https://doi.org/10.1111/cts.70310hepaticpharmacokineticsphase Irenal |
| spellingShingle | Megumi Iwai Nakyo Heo Kentaro Hashimoto Sayuri Guro Selina Moy Anna Spence Tomasz Wojtkowski Lauren Benner Melanie Helmick Tong Zhu Brian C. Ferslew Pharmacokinetics of Bocidelpar, ASP0367, in Renal and Hepatic Impairment: Results From Two Phase 1 Studies Clinical and Translational Science hepatic pharmacokinetics phase I renal |
| title | Pharmacokinetics of Bocidelpar, ASP0367, in Renal and Hepatic Impairment: Results From Two Phase 1 Studies |
| title_full | Pharmacokinetics of Bocidelpar, ASP0367, in Renal and Hepatic Impairment: Results From Two Phase 1 Studies |
| title_fullStr | Pharmacokinetics of Bocidelpar, ASP0367, in Renal and Hepatic Impairment: Results From Two Phase 1 Studies |
| title_full_unstemmed | Pharmacokinetics of Bocidelpar, ASP0367, in Renal and Hepatic Impairment: Results From Two Phase 1 Studies |
| title_short | Pharmacokinetics of Bocidelpar, ASP0367, in Renal and Hepatic Impairment: Results From Two Phase 1 Studies |
| title_sort | pharmacokinetics of bocidelpar asp0367 in renal and hepatic impairment results from two phase 1 studies |
| topic | hepatic pharmacokinetics phase I renal |
| url | https://doi.org/10.1111/cts.70310 |
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