Changes Observed During The Screening Period In Patients Enrolled In The Sitagliptin Clinical Study Mk-0431-P083

MK-0431-P083, a 54-week phase III study of the DPP-4 inhibitor sitagliptin as initial oral therapy in patients 10-17 years of age with T2D was initiated in 2012 and completed enrollment in 2018. After informed consent was obtained, patient screening was initiated with a screening visit (V1), followed by a single-blind, placebo run-in (V2) for 1 week, after which they were randomized (V3, N = 201). The changes observed in select laboratory and anthropometric parameters in these 201 patients between V1 and V3 (~25 days), and adverse events (AEs) reported during the 1-week placebo run-in (V2 to V3), were summarized in a preliminary analysis. Results: (mean ± SD [95% confidence interval]) are presented below. Between V1 and V3 (25 ± 7 days, median 23 days), A1C decreased from 7.72 ± 1.02% to 7.49 ± 1.03%, a change (Δ) of -0.23 ± 0.67% [-0.32, -0.13], while FPG was unchanged. Changes were also observed in ALT (Δ: -2.55 ± 11.21 IU [-4.15, -0.95]) and AST (Δ: -1.93 ± 9.08 IU [-3.22, -0.63]). Weight and lipid parameters were unchanged. Between V2 and V3, 75 AEs were reported for 40 patients (~20% of the randomized patients). Of these AEs, 3 were assessed to be drug-related by the investigators: 2 AEs of nervousness and dyspepsia in 1 patient, and an AE of worsening gastroesophageal reflux in another. None of the 75 AEs were assessed to be severe, and none led to discontinuation from the study. These data suggest that changes may be observed in glycemic parameters during a screening period of <4 weeks. Furthermore, during the 1-week placebo run-in period, AEs were reported for nearly 20% of patients; remarkably, despite being told that patients received only placebo during this period, investigators considered some of the AEs to be drug-related. Disclosure C.A. Rosario: None. M.Y. Jalaludin: Advisory Panel; Self; Novo Nordisk Inc. Research Support; Self; Merck Sharp & Dohme Corp., Novo Nordisk Inc. R. Garcia: None. R.S. Newfield: Research Support; Self; Bristol-Myers Squibb Company, Daiichi Sankyo Company, Limited, Eli Lilly and Company, University of California and Rady Children's Hospital, San Diego. Y. Samoilova: None. N. Shehadeh: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi-Aventis. Speaker's Bureau; Self; Eli Lilly and Company, Merck Sharp & Dohme Corp. A. Pong: None. M. Zilli: Employee; Self; Merck Sharp & Dohme Corp. Stock/Shareholder; Self; Merck Sharp & Dohme Corp. C.K. Saha: Research Support; Self; Indiana University School of Medicine. S.S. Engel: Employee; Self; Merck & Co., Inc. Stock/Shareholder; Self; Merck & Co., Inc. P. Zeitler: Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Janssen Research & Development, Merck & Co., Inc., Novo Nordisk Inc. K.D. Kaufman: Employee; Self; Merck & Co., Inc. Stock/Shareholder; Self; Merck & Co., Inc. R. Shankar: Employee; Spouse/Partner; AstraZeneca. Employee; Self; Merck & Co., Inc. Employee; Spouse/Partner; NGM Biopharmaceuticals. Funding Merck & Co., Inc.