A Pan-Inhibitor of Phosphate Transporters AP306 in Hemodialysis Patients
Introduction: Hyperphosphatemia in patients undergoing dialysis is not well-controlled. AP306 is a pan-inhibitor of phosphate transporters, designed to block the active uptake of phosphate through the gastrointestinal tract. Methods: In this phase 2 randomized, active-controlled, open-label study, h...
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Elsevier
2025-04-01
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| Series: | Kidney International Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2468024925000634 |
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| author | Li Wang Li Zuo Ming Shi Leyi Gu Kunling Ma Pei Wang Yu Wang Qun Luo Menghua Chen Ping Zhang Hongli Jiang Guisen Li Weifeng Zhang Yingxue Cathy Liu Qing Zhao |
| author_facet | Li Wang Li Zuo Ming Shi Leyi Gu Kunling Ma Pei Wang Yu Wang Qun Luo Menghua Chen Ping Zhang Hongli Jiang Guisen Li Weifeng Zhang Yingxue Cathy Liu Qing Zhao |
| author_sort | Li Wang |
| collection | DOAJ |
| description | Introduction: Hyperphosphatemia in patients undergoing dialysis is not well-controlled. AP306 is a pan-inhibitor of phosphate transporters, designed to block the active uptake of phosphate through the gastrointestinal tract. Methods: In this phase 2 randomized, active-controlled, open-label study, hemodialysis patients with serum phosphate between 5.5 and 9.0 mg/dl were randomized to receive either AP306 or sevelamer carbonate for 12 weeks. The primary outcome was the change in serum phosphate levels from baseline until the therapy ceased. AP306 was initiated at 75 mg and adjusted stepwise to 125 mg and 150 mg orally thrice daily every 4 weeks, to maintain serum phosphate between 3.5 and 5.5 mg/dl. Sevelamer levels were adjusted using the same criteria and frequency. Results: A total of 27 patients were randomized to receive AP306 and 28 to receive sevelamer. At the end-of-treatment, both AP306 and sevelamer resulted in a significant decrease from baseline in serum phosphate by 2.51 mg/dl (95% confidence interval [CI]:−3.07 to −1.92; P < 0.001) and 1.08 mg/dl (95% CI: −1.58 to −0.59), respectively. The proportions of patients achieving the recommended range as per the Kidney Disease: Improving Global Outcomes guidelines (2.5–4.5 mg/dl) were about 20% higher in AP306 than in sevelamer, starting from treatment week 5. The most reported adverse events (AEs) associated with AP306 were gastrointestinal disorders (51.9%), most of which were mild to moderate diarrhea (44.4%). Conclusion: AP306 monotherapy significantly reduced serum phosphate levels and substantially improved the serum phosphate control rate in hemodialysis patients with hyperphosphatemia. AP306 was safe and well-tolerated. |
| format | Article |
| id | doaj-art-43a1dc5eee4f404daea2172ec5f5f5dd |
| institution | Kabale University |
| issn | 2468-0249 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Kidney International Reports |
| spelling | doaj-art-43a1dc5eee4f404daea2172ec5f5f5dd2025-08-20T03:25:54ZengElsevierKidney International Reports2468-02492025-04-011041143115110.1016/j.ekir.2025.01.038A Pan-Inhibitor of Phosphate Transporters AP306 in Hemodialysis PatientsLi Wang0Li Zuo1Ming Shi2Leyi Gu3Kunling Ma4Pei Wang5Yu Wang6Qun Luo7Menghua Chen8Ping Zhang9Hongli Jiang10Guisen Li11Weifeng Zhang12Yingxue Cathy Liu13Qing Zhao14Department of Nephrology and Institute of Nephrology, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Sichuan Clinical Research Centre for Kidney Diseases, Chengdu, Sichuan, China; Correspondence: Li Wang, Department of Nephrology and Institute of Nephrology, Sichuan Provincial People's Hospital, 32# W. Sec 2, 1st Ring Rd., Chengdu, Sichuan Province, P.R. China.Department of Nephrology, Peking University People’s Hospital, Beijing, ChinaDepartment of Nephrology, Blood Purification Center, Renmin Hospital of Wuhan University, Wuhan, ChinaMolecular Cell Lab for Kidney Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Department of Nephrology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Shanghai Peritoneal Dialysis Research Center, Uremia Diagnosis and Treatment Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Nephrology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, ChinaDepartment of Nephrology, Blood Purification Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Nephrology, the First Affiliated Hospital of Nanchang University, Nanchang, ChinaKidney Disease Center, Ningbo No. 2 Hospital, Ningbo, ChinaDepartment of Nephrology, General Hospital of Ningxia Medical University, Yinchuan, ChinaKidney Disease Center, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, ChinaBlood Purification Center, the First Affiliated Hospital of Xi'an Jiaotong University, Xi’an, ChinaDepartment of Nephrology and Institute of Nephrology, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Sichuan Clinical Research Centre for Kidney Diseases, Chengdu, Sichuan, ChinaClinical Science, Shanghai Alebund Pharmaceuticals Limited, Shanghai, ChinaBiometrics, Shanghai Alebund Pharmaceuticals Limited, Shanghai, ChinaClinical Science, Shanghai Alebund Pharmaceuticals Limited, Shanghai, ChinaIntroduction: Hyperphosphatemia in patients undergoing dialysis is not well-controlled. AP306 is a pan-inhibitor of phosphate transporters, designed to block the active uptake of phosphate through the gastrointestinal tract. Methods: In this phase 2 randomized, active-controlled, open-label study, hemodialysis patients with serum phosphate between 5.5 and 9.0 mg/dl were randomized to receive either AP306 or sevelamer carbonate for 12 weeks. The primary outcome was the change in serum phosphate levels from baseline until the therapy ceased. AP306 was initiated at 75 mg and adjusted stepwise to 125 mg and 150 mg orally thrice daily every 4 weeks, to maintain serum phosphate between 3.5 and 5.5 mg/dl. Sevelamer levels were adjusted using the same criteria and frequency. Results: A total of 27 patients were randomized to receive AP306 and 28 to receive sevelamer. At the end-of-treatment, both AP306 and sevelamer resulted in a significant decrease from baseline in serum phosphate by 2.51 mg/dl (95% confidence interval [CI]:−3.07 to −1.92; P < 0.001) and 1.08 mg/dl (95% CI: −1.58 to −0.59), respectively. The proportions of patients achieving the recommended range as per the Kidney Disease: Improving Global Outcomes guidelines (2.5–4.5 mg/dl) were about 20% higher in AP306 than in sevelamer, starting from treatment week 5. The most reported adverse events (AEs) associated with AP306 were gastrointestinal disorders (51.9%), most of which were mild to moderate diarrhea (44.4%). Conclusion: AP306 monotherapy significantly reduced serum phosphate levels and substantially improved the serum phosphate control rate in hemodialysis patients with hyperphosphatemia. AP306 was safe and well-tolerated.http://www.sciencedirect.com/science/article/pii/S2468024925000634dialysisend-stage kidney diseasehyperphosphatemiaphosphate transporter |
| spellingShingle | Li Wang Li Zuo Ming Shi Leyi Gu Kunling Ma Pei Wang Yu Wang Qun Luo Menghua Chen Ping Zhang Hongli Jiang Guisen Li Weifeng Zhang Yingxue Cathy Liu Qing Zhao A Pan-Inhibitor of Phosphate Transporters AP306 in Hemodialysis Patients Kidney International Reports dialysis end-stage kidney disease hyperphosphatemia phosphate transporter |
| title | A Pan-Inhibitor of Phosphate Transporters AP306 in Hemodialysis Patients |
| title_full | A Pan-Inhibitor of Phosphate Transporters AP306 in Hemodialysis Patients |
| title_fullStr | A Pan-Inhibitor of Phosphate Transporters AP306 in Hemodialysis Patients |
| title_full_unstemmed | A Pan-Inhibitor of Phosphate Transporters AP306 in Hemodialysis Patients |
| title_short | A Pan-Inhibitor of Phosphate Transporters AP306 in Hemodialysis Patients |
| title_sort | pan inhibitor of phosphate transporters ap306 in hemodialysis patients |
| topic | dialysis end-stage kidney disease hyperphosphatemia phosphate transporter |
| url | http://www.sciencedirect.com/science/article/pii/S2468024925000634 |
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