TY - JOUR
T1 - Clinical trial
T2 - a single-centre, randomised, controlled trial of tradipitant on satiation, gastric functions, and serum drug levels in healthy volunteers
AU - Khanna, Lehar
AU - Zheng, Ting
AU - Atieh, Jessica
AU - Torres, Monique
AU - Busciglio, Irene
AU - Carlin, Jesse L.
AU - Xiao, Michael
AU - Harmsen, William S.
AU - Camilleri, Michael
N1 - Publisher Copyright:
© 2022 John Wiley & Sons Ltd.
PY - 2022/7
Y1 - 2022/7
N2 - Background: Tradipitant, an NK1 receptor antagonist, improved symptoms in patients with gastroparesis. It is unclear whether these effects are mediated centrally (e.g., vomiting centre) or on gastric functions. As a class, NK1 antagonists may retard gastric emptying (GE) or increase fasting and postprandial gastric volumes (GV). Aim: To evaluate the effects of tradipitant relative to placebo on gastric motor functions, satiation, postprandial symptoms, and pharmacokinetics. Methods: We conducted a randomised, double-blind, placebo-controlled, single-centre study of tradipitant 85 mg or matching placebo b.i.d. for 9 consecutive days in 24 healthy volunteers. During the last 2 days of treatment, participants underwent scintigraphic measurements of GE of 320 kcal egg meal, fasting and postprandial GV by SPECT, and satiation by nutrient drink ingested to maximum tolerated volume (MTV) and symptoms 30 min later. Treatments were compared by Wilcoxon rank sum test. The study had 80% power to detect group differences of 23.6% in GV and 29.2% in GE T1/2. Results: The two groups of healthy participants were well balanced based on demographic features, age, and BMI. There were nonsignificant positive correlations between blood levels of tradipitant and accommodation GV and GE at 4 h. There were no significant effects of tradipitant, 85 mg b.i.d. for 9 days compared to placebo on GE, GV, satiation, or symptoms 30 min after MTV. Conclusion: Tradipitant, 85 mg b.i.d., does not significantly affect gastric motor functions (GV or GE). Importantly, there was no retardation of GE by tradipitant, which is important in relation to its potential use in patients with gastroparesis. Clinic trials registry: ClinicalTrials.gov #NCT04849559.
AB - Background: Tradipitant, an NK1 receptor antagonist, improved symptoms in patients with gastroparesis. It is unclear whether these effects are mediated centrally (e.g., vomiting centre) or on gastric functions. As a class, NK1 antagonists may retard gastric emptying (GE) or increase fasting and postprandial gastric volumes (GV). Aim: To evaluate the effects of tradipitant relative to placebo on gastric motor functions, satiation, postprandial symptoms, and pharmacokinetics. Methods: We conducted a randomised, double-blind, placebo-controlled, single-centre study of tradipitant 85 mg or matching placebo b.i.d. for 9 consecutive days in 24 healthy volunteers. During the last 2 days of treatment, participants underwent scintigraphic measurements of GE of 320 kcal egg meal, fasting and postprandial GV by SPECT, and satiation by nutrient drink ingested to maximum tolerated volume (MTV) and symptoms 30 min later. Treatments were compared by Wilcoxon rank sum test. The study had 80% power to detect group differences of 23.6% in GV and 29.2% in GE T1/2. Results: The two groups of healthy participants were well balanced based on demographic features, age, and BMI. There were nonsignificant positive correlations between blood levels of tradipitant and accommodation GV and GE at 4 h. There were no significant effects of tradipitant, 85 mg b.i.d. for 9 days compared to placebo on GE, GV, satiation, or symptoms 30 min after MTV. Conclusion: Tradipitant, 85 mg b.i.d., does not significantly affect gastric motor functions (GV or GE). Importantly, there was no retardation of GE by tradipitant, which is important in relation to its potential use in patients with gastroparesis. Clinic trials registry: ClinicalTrials.gov #NCT04849559.
KW - accommodation
KW - gastric emptying
KW - neurokinin
KW - receptor
KW - volume
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U2 - 10.1111/apt.17065
DO - 10.1111/apt.17065
M3 - Article
C2 - 35644931
AN - SCOPUS:85130989547
SN - 0269-2813
VL - 56
SP - 224
EP - 230
JO - Alimentary Pharmacology and Therapeutics
JF - Alimentary Pharmacology and Therapeutics
IS - 2
ER -