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Abstract: PO1633

Atrasentan Exhibits a Consistent, Predictable Pharmacokinetic Profile Among Healthy Asian Adults

Session Information

Category: Glomerular Diseases

  • 1203 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Rastogi, Anjay, University of California Los Angeles David Geffen School of Medicine, Los Angeles, California, United States
  • Lv, Jicheng, Peking University First Hospital, Beijing, Beijing, China
  • Catanzaro, David A., Chinook Therapeutics Inc, Seattle, Washington, United States
  • Tong, Vince, Chinook Therapeutics Inc, Seattle, Washington, United States
  • Suzuki, Yusuke, Juntendo Daigaku Igakubu Daigakuin Igaku Kenkyuka, Bunkyo-ku, Tokyo, Japan
Background

Atrasentan, a potent and selective endothelin-A receptor antagonist, is under investigation for reducing proteinuria and preserving kidney function in IgA nephropathy and other glomerular diseases. Two phase 1 studies evaluated the pharmacokinetics (PK) and safety of atrasentan in healthy adults of Chinese (Study M11-521) and Japanese (Study M11-522) parentage.

Methods

Study M11-521 was an open-label, randomized (for single-dose regimens), single-center study of single and multiple doses of atrasentan in 36 healthy Chinese adults. Single doses of atrasentan tablets (0.5, 1, or 1.5 mg) were administered in Part I, and multiple once-daily doses of atrasentan 1.5 mg were administered in Part II. Study M11-522 was a double-blind, randomized, placebo-controlled, single-center study of single doses of atrasentan (0.5, 0.75, or 1.25 mg) in 36 healthy Japanese adults. Blood samples were collected for analysis of plasma PK parameters, including the area under the plasma concentration-time curve (AUC) and the maximum observed plasma concentration (Cmax).

Results

In Study M11-521, atrasentan AUC increased proportionally with dose in the 0.5 mg to 1.5 mg dose range, and Cmax increased proportionally with dose in the 1 mg to 1.5 mg dose range. No statistically significant differences were observed in either the dose-normalized AUC∞ for the comparison of the 1.5 mg and 0.5 mg dose groups (P ≥ 0.260) or the dose-normalized Cmax for the comparison of the 1.5 mg and the 1 mg dose groups (P = 0.279). In Study M11-522, a linear increase in atrasentan mean AUC∞ was observed across the 0.5 to 1.25 mg dose range; dose-normalized mean AUC∞ did not show any statistically significant difference across the doses (P = 0.735). Atrasentan was generally well tolerated. No clinically significant vital signs, electrocardiogram activity, or laboratory measurements were observed, and no apparent significant differences among the dose regimens were found with respect to safety.

Conclusion

Dose-proportional increases in AUC were observed across the studied range, which includes the 0.75 mg dose being studied in ongoing clinical trials. These data support the safety and tolerability of atrasentan and suggest a consistent and predictable PK profile among patients of Asian descent.

Funding

  • Commercial Support –