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Sarah J Bond,1 Nathan Parikh,1 Shrey Majmudar,1 Sabrina Pin,1 Christine Wang,1 Lauren Willis,1 Susanne B Haga1,2 1Duke University, Durham, NC, 27708, USA; 2Duke University School of Medicine, Durham, NC, 27708, USACorrespondence: Susanne B HagaDuke University, 101 Science Drive, Box 3382, Durham, NC, 27708, USA, Tel +1 919 684 0325, Fax +1 919 681 8973, Email susanne.haga@duke.eduBackground: Despite the purported advantages and potential efficacy of mHealth interventions to promote wellness in children, adolescents, and young adults, it is not clear what areas have been explored and the challenges reported in the biomedical literature.Methods: We conducted a scoping review of publications between 2015 and 2019.Results: We identified 54 papers that met our inclusion criteria. Studies were conducted in 21 countries and ranged in size from six to 9851 participants (median: 184). A total of 41% of studies enrolled adolescents only (n = 19). Of the seven types of mHealth interventions identified, apps were the most common intervention (59%; n = 32) evaluated and 44% of the studies evaluated two or more interventions. The most common topic of the studies reviewed was sexual and reproductive health (24%; n = 13).Conclusion: Most pediatric mHealth intervention studies are conducted in adolescents in large part, and sexual and reproductive health is the most commonly studied topic. With the easy and widespread accessibility to smartphone technology, the use of mobile apps for wellness interventions will likely continue to expand to other wellness topics.Keywords: mHealth, wellness, children, adolescents, young adults

D Alexander Oh, Neha Parikh, Varun Khurana, Christina Cognata Smith, Santosh VetticadenINSYS Therapeutics, Inc., Chandler, AZ, USA Abstract: Dronabinol is a pharmaceutical tetrahydrocannabinol originally developed as an oral capsule. A dronabinol oral solution was recently approved, and the effects of food on absorption and bioavailability of the oral solution versus capsules were compared in an open-label, single-dose, 3-period crossover study. Healthy volunteers were randomized to either dronabinol oral solution 4.25 mg (fed) or dronabinol capsule 5 mg (fed or fasted). Dosing was separated by a 7-day washout period. Plasma pharmacokinetics were evaluated for dronabinol and its major metabolite, 11-hydroxy-delta-9-tetrahydrocannabinol (11-OH-∆9-THC). Pharmacokinetic data were available for analysis in 54 volunteers. In the fed state, initial dronabinol absorption was faster with oral solution versus capsule (mean time to the first measurable concentration, 0.15 vs 2.02 hours, respectively), with 100% and 15% of volunteers, respectively, having detectable plasma dronabinol levels 30 minutes postdose. There was less interindividual variability in plasma dronabinol concentration during early absorption with oral solution versus capsule. Compared with the fasted state, mean area under the plasma concentration–time curve from time zero to the last measurable concentration (AUC0-t) increased by 2.1- and 2.4-fold for dronabinol oral solution and capsule, respectively, when taken with food. Mean time to maximum plasma concentration was similarly delayed for dronabinol oral solution with food (7.7 hours) and capsule with food (5.6 hours) versus capsule with fasting (1.7 hours). Under fed conditions, AUC0–t and area under the plasma concentration–time curve from time zero to infinity were similar for the oral solution versus capsule based on 11-OH-∆9-THC levels. An appreciable food effect was observed for dronabinol oral solution and capsules. Dronabinol oral solution may offer therapeutic benefit to patients, given its rapid and lower interindividual absorption variability versus dronabinol capsule. Keywords: bioavailability, dronabinol, Marinol, pharmacokinetics, observer variation

Neha Parikh,1 William G Kramer,2 Varun Khurana,1 Christina Cognata Smith,1 Santosh Vetticaden,1 1INSYS Therapeutics, Inc., Chandler, AZ, USA; 2Kramer Consulting LLC, North Potomac, MD, USA Background: Dronabinol, a pharmaceutical Δ-9-tetrahydrocannabinol, was originally developed as an oral capsule. This study evaluated the bioavailability of a new formulation, dronabinol oral solution, versus a dronabinol capsule formulation. Methods: In an open-label, four-period, single-dose, crossover study, healthy volunteers were randomly assigned to one of two treatment sequences (T-R-T-R and R-T-R-T; T = dronabinol 4.25 mg oral solution and R = dronabinol 5 mg capsule) under fasted conditions, with a minimum 7-day washout period between doses. Analyses were performed on venous blood samples drawn 15 minutes to 48 hours postdose, and dronabinol concentrations were assayed by liquid chromatography–tandem mass spectrometry. Results: Fifty-one of 52 individuals had pharmacokinetic data for analysis. The 90% confidence interval of the geometric mean ratio (oral solution/capsule) for dronabinol was within the 80%–125% bioequivalence range for area under the plasma concentration–time curve (AUC) from time zero to last measurable concentration (AUC0–t) and AUC from time zero to infinity (AUC0–∞). Maximum plasma concentration was also bioequivalent for the two dronabinol formulations. Intraindividual variability in AUC0–∞ was >60% lower for dronabinol oral solution 4.25 mg versus dronabinol capsule 5 mg. Plasma dronabinol concentrations were detected within 15 minutes postdose in 100% of patients when receiving oral solution and in

Richard S Finn,1 Renuka Iyer,2 Richard S Kalman,3 Neehar D Parikh,4 Roniel Cabrera,5 Svetlana Babajanyan,6 Ahmed O Kaseb7 1Department of Medicine, University of California, Los Angeles, CA, USA; 2Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA; 3Department of Medicine, Einstein Medical Center, Philadelphia, PA, USA; 4Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, USA; 5Department of Medicine, University of Florida Health, Gainesville, FL, USA; 6US Medical Affairs, Oncology, Bayer Healthcare, Whippany, NJ, USA; 7Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USACorrespondence: Richard S Finn, Department of Medicine, University of California, Los Angeles, CA, USA, Tel +1-310-586-2091, Email rfinn@mednet.ucla.eduIntroduction: While several systemic therapies are available for unresectable hepatocellular carcinoma (uHCC), there is a lack of granular real-world evidence to support the efficacy and safety of these therapies. The REFINE study evaluated safety and effectiveness of regorafenib in a global population under real-world practice conditions. This sub-analysis describes the safety and effectiveness of regorafenib among the United States (US) subset of patients in the REFINE study relative to patients in the non-US subset.Materials and Methods: REFINE was an international, prospective, multicenter observational study. Eligible patients were those with uHCC for whom a decision to treat with regorafenib had already been made. The primary study endpoint was the frequency of documented treatment-emergent adverse events (TEAEs). Additional endpoints included overall survival and progression-free survival. Groups were compared descriptively.Results: Of 1005 patients, 65 were from the US and 940 were from other countries. 91% of patients in the US subset (n=59) and 92% in the non-US subset (n=862) experienced ≥ 1 TEAE. Common adverse events (AEs) included gastrointestinal disorders, fatigue, and hand-foot skin reaction. Median overall survival for patients in the US subset was 11.4 months (interquartile range [IQR]: 4.7– 25.4) and 13.2 months (IQR: 5.8– 26.3) in the non-US subset. Median progression-free survival was 3.4 months (IQR: 2.4– 6.1) for patients in the US subset and 3.9 months (IQR: 2.2– 8.5) in the non-US subset.Conclusion: Regorafenib was associated with similar safety and effectiveness outcomes for patients in the US and non-US subsets of the REFINE study. Differences in the incidence of certain AEs may be due to differences in treatment management between study sites or baseline disease status. These findings are consistent with the phase 3 RESORCE trial and corroborate the safety and effectiveness of regorafenib as a subsequent-line treatment in US patients with uHCC.Keywords: hepatocellular carcinoma, regorafenib, sorafenib, observational study