751-P: First-in-Human, Single and Repeated Dose Study of SCO-267, a GPR40 Full Agonist, in Healthy Adults and Subjects with Glucose Intolerance

Abstract

The clinical potential of SCO-267, an orally available allosteric full agonist against GPR40 that regulates islet and gut hormone secretion, is largely unknown. Here, we present the first clinical study using the GPR40 full agonist. A randomized, single-center, double-blind, placebo-controlled, phase 1 study was conducted to investigate safety, tolerability, and pharmacokinetics as primary endpoints and pharmacodynamics as secondary endpoints of single (5-320 mg) and repeated doses (80 and 160 mg, Q.D.) of SCO-267 in healthy adults and subjects with glucose intolerance (HbA1c range 6.6-8.8%). SCO-267 was generally safe and well tolerated at all doses up to 4 days. The plasma SCO-267 concentration increased generally dose-dependently and its pharmacokinetic profiles suggests the potential for once-daily oral dosing in a clinical setting. The pharmacokinetic profiles of SCO-267 was similar between Japanese and Caucasian subjects, and healthy subjects and those with glucose intolerance. Pharmacokinetic profiles of SCO-267 in healthy adults were unaltered with repeated doses. SCO-267 was hardly detected in urine, suggesting that it is eliminated by non-renal mechanisms. SCO-267 single dose (40 and 80 mg) stimulated secretion of insulin, glucagon, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and peptide YY (PYY), and normalized glucose intolerance during an oral glucose tolerance test in subjects with glucose intolerance. SCO-267 repeated dose (80 and 160 mg) stimulated secretion of insulin, glucagon, GLP-1, GIP, and PYY in healthy adults. In conclusion, SCO-267 was safe, well tolerated, and pharmacokinetic profiles support a once-daily dosing regimen. SCO-267 further stimulated islet and gut hormone secretion and normalized glucose tolerance in humans. These findings support the further development of SCO-267 for diabetes, obesity, and nonalcoholic steatohepatitis. Disclosure H. Nishizaki: Employee; Self; Scohia Pharma Inc. O. Matsuoka: None. M. Achira: Employee; Self; PRA Health Sciences KK. T. Kagawa: Employee; Self; Scohia Pharma Inc. M. Watanabe: Employee; Self; Scohia Pharma Inc. Y. Moritoh: Employee; Self; Scohia Pharma Inc.