766-P: Safety and Tolerability of Once-Weekly GL0034 (Utreglutide) in Healthy Individuals—A Multiple Ascending Dose Study

Abstract

GL0034 (GL) is being developed as a once-weekly, long-acting glucagon-like peptide 1 receptor agonist (GLP-1RA). This phase 1 study assessed the safety and tolerability of multiple ascending doses of GL. Healthy individuals (N=36) with BMI 18 to 28 kg/m2 were randomized (9:3) to subcutaneous GL or placebo. Two groups of nine individuals each received a fixed dose of 450 μg (cohort 1) or 680 μg (cohort 2) during four weeks; a third group was treated for eight weeks, with two weekly doses of 450 μg, followed by two doses of 900 μg and four doses of 1,520 μg (cohort 3). Safety biomarkers and key exploratory pharmacodynamic effects including fasting insulin and glucose, alanine transaminase and body weight were assessed. GL related adverse effects were mainly gastrointestinal with dose-dependent nausea, vomiting and decreased appetite. Fasting insulin was decreased in cohort 2 and cohort 3 on day 23 and 51 respectively following treatment with GL with a corresponding reduction in homeostatic model assessment for insulin resistance (HOMA-IR). At day 51, alanine transaminase levels decreased from baseline in cohort 3 versus an increase in placebo. Dose-dependent decreases in body weight were measured in cohorts 1, 2 and 3, respectively, compared to baseline, and were sustained through days 50 and 78. In conclusion, GL was well tolerated and efficacious in healthy individuals with normal weight. Disclosure R.Thennati: None. A.Garcia-ocana: Consultant; Sun Pharmaceutical Industries Ltd. G.A.Rutter: Consultant; Sun Pharmaceutical Industries Ltd. R.E.Pratley: Other Relationship; Bayer Inc., Corcept Therapeutics, Dexcom, Inc., Gasherbrum Bio, Inc., Hanmi Pharm. Co., Ltd., Hengrui (USA) Ltd., Merck Sharp & Dohme Corp., Novo Nordisk, Pfizer Inc., Rivus Pharmaceuticals Inc., Sanofi, Scohia Pharma Inc., Sun Pharmaceutical Industries Ltd. B.Thorens: Advisory Panel; Sun Pharmaceutical Industries Ltd. T.Vilsbøll: Consultant; AstraZeneca, Boehringer Ingelheim Inc., Gilead Sciences, Inc., Eli Lilly and Company, Mundipharma, Merck & Co., Inc., Novo Nordisk A/S, Sanofi, Sun Pharmaceutical Industries Ltd., Bristol-Myers Squibb Company. V.S.Burade: None. M.Natarajan: None. P.Shahi: None. R.Nagaraja: None. S.T.Panchal: None. S.K.Agrawal: None. B.Jandrain: None. T.Duvauchelle: None.