MEDI0382 is an oxyntomodulin-like peptide with targeted GLP-1 and glucagon receptor activity under development for T2DM treatment. Patients with T2DM have a high risk for cardiovascular disease. In an open-label, crossover, phase 1 study (NCT03347968), we evaluated the effect of MEDI0382 (SC; titrated up to 300 µg for 25 days) on the pharmacodynamics (PD) and PK of warfarin (PO; 25 mg on day [d] 2 [warfarin alone] and d 27 [warfarin + MEDI0382]) and PD of esmolol (IV; 200 µg/kg/min for 90 min on d 1 [esmolol alone] and d 26 [esmolol + MEDI0382]) in healthy volunteers (N = 22). Coprimary endpoints were prothrombin time (PT) maximum international normalized ratio (INRmax) and INRAUC of warfarin with MEDI0382, and change in heart rate from rest to after a 9-minute treadmill test (Bruce Protocol) with esmolol and MEDI0382. The coprimary endpoints were analyzed using paired t-tests. INRmax and INRAUC values were log transformed for analysis. MEDI0382 had no effect on PT INRmax, INRAUC (Table), or the PK profile of warfarin. Similar changes in heart rate with the treadmill test were observed with esmolol alone or with esmolol and MEDI0382 (Table). MEDI0382 resulted in an increased incidence of nausea and vomiting. There were no serious or severe adverse events. These results support co-administration of MEDI0382 and warfarin or esmolol and do not suggest safety concerns.

H.A. Coleman: None. M. Petrone: Employee; Self; MedImmune. T.M. Petrohoy: None. Y. Yang: Employee; Self; MedImmune. L.J. Sanford: None. L. Hansen: Employee; Self; AstraZeneca, MedImmune. Stock/Shareholder; Self; Bristol-Myers Squibb Company, Novo Nordisk A/S. A. Flor: Employee; Self; AstraZeneca.

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