Proof-of-concept study to evaluate the safety and efficacy of saroglitazar in patients with primary biliary cholangitis
| Autor: | Cynthia Levy, Deven Parmar, Andrew deLemos, Simona Rossi, Aasim Sheikh, Naga Chalasani, Nikolaos Pyrsopoulos, Edward Mena, David S. Goldberg, Stephen H. Caldwell, Farheen Shaikh, Ravi Ravinuthala, Raj Vuppalanchi, James D. Bainbridge |
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| Rok vydání: | 2022 |
| Předmět: |
Male
Agonist medicine.medical_specialty medicine.drug_class Placebo Gastroenterology Placebos Double-Blind Method Internal medicine Humans Medicine Pyrroles In patient Phenylpropionates Hepatology Liver Cirrhosis Biliary business.industry Incidence (epidemiology) Saroglitazar Middle Aged medicine.disease Ursodeoxycholic acid Treatment Outcome Alkaline phosphatase Female business Dyslipidemia medicine.drug |
| Zdroj: | Journal of Hepatology. 76:75-85 |
| ISSN: | 0168-8278 |
| Popis: | Saroglitazar is a novel peroxisome proliferator-activated receptor (PPAR) agonist with dual agonistic properties (α/γ). Due to a strong mechanistic rationale, we aimed to test the safety and efficacy of saroglitazar in patients with primary biliary cholangitis (PBC) who were either ursodeoxycholic acid (UDCA) resistant or intolerant.In this double-blind, phase II proof-of-concept trial, 37 patients with PBC were randomized to saroglitazar 4 mg (n = 13), saroglitazar 2 mg (n = 14), or placebo (n = 10) daily for 16 weeks. The primary efficacy endpoint was the reduction in alkaline phosphatase (ALP) level at Week 16.A significant reduction of mean ALP levels was observed at Week 16 relative to baseline in both the saroglitazar 4 mg (least-squares [LS] mean =-163.3 U/L, SE = 25.1, p0.001) and 2 mg (LS mean =-155.8 U/L, SE = 24.4, p0.001) groups, compared with placebo (LS mean =-21.1 U/L, SE = 28.9). Treatment with saroglitazar resulted in a rapid reduction of ALP concentration at Week 4 that was sustained through the study duration. At least 1 treatment-emergent adverse event occurred in 11 (84.6%) patients in the saroglitazar 4 mg group, in 12 (85.7%) patients in the 2 mg group and in 8 (80%) patients in the placebo group. Study drug was discontinued in 4 patients (3 patients in the 4 mg group and 1 patient in the 2 mg group) due to aminotransferase increases that promptly returned to baseline values after drug discontinuation.Saroglitazar at 2 mg and 4 mg daily was tolerated and resulted in rapid and sustained improvements in ALP. Further studies are underway at a daily dose of 2 mg and 1 mg due to the higher incidence of elevated liver enzymes observed with the 4 mg dose. CLINICALTRIALS.NCT03112681 LAY SUMMARY: Saroglitazar resulted in a rapid and sustained improvement in alkaline phosphatase levels in patients with primary biliary cholangitis. The mean percentage reductions in alkaline phosphatase levels were 49% and 51% in the saroglitazar 4 mg and 2 mg groups compared to 3% in the placebo group. |
| Databáze: | OpenAIRE |
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