Clinical trial: a single‐centre, randomised, controlled trial of tradipitant on satiation, gastric functions, and serum drug levels in healthy volunteers

Abstract

Summary 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 http://clinicaltrials.gov #NCT04849559.

Editorial: tradipitant has promise for treating gastroparesis but leaves gastric function alone—authors’ reply

“…Ehrenpreis and Kruchko 1 for their editorial comments on the effects of tradipitant on gastric functions. 2 We agree with their appraisal of the content of our article relative to the safety and effects of tradipitant on gastric functions in healthy participants. However, the premises that lead to the conclusion that treatments for gastroparesis should focus on symptom relief rather than changes in gastric emptying are erroneous.…”

“…We thank Drs. Ehrenpreis and Kruchko 1 for their editorial comments on the effects of tradipitant on gastric functions 2 . We agree with their appraisal of the content of our article relative to the safety and effects of tradipitant on gastric functions in healthy participants.…”

Editorial: tradipitant has promise for treating gastroparesis but leaves gastric function alone

“…6 The purpose of the study by Khanna et al was to measure the physiological effects of tradipitant on gastric function including gastric motor function, satiation and post-prandial symptoms. 7 The authors performed a variety of tests on a group of healthy individuals including scintigraphic measurements of solid gastric emptying, fasting and postprandial gastric volumes by SPECT and satiation after ingestion of a nutrient drink. Overall, tradipitant demonstrated little effect on gastric function other than an increase in the first phase of gastric emptying, a physiological marker for post-prandial filling and distension of the stomach.…”

“…8 Tradipitant appears to be well tolerated with a similar side effect profile as placebo. 7 However, as announced this year, the drug failed to reach a significant difference in the primary endpoint (change of nausea severity from baseline at week 12 of treatment) of the Phase 3 clinical trial. 8 In fact, improvement in a variety of symptoms of gastroparesis was seen in both the tradipitant and placebo groups.…”

“…Neurokinin protein receptors such as NK1 are required for tachykinin‐related GI function, and NK1 receptor aberrancy may result in gastric dysfunction, nausea and vomiting 6 . The purpose of the study by Khanna et al was to measure the physiological effects of tradipitant on gastric function including gastric motor function, satiation and post‐prandial symptoms 7 . The authors performed a variety of tests on a group of healthy individuals including scintigraphic measurements of solid gastric emptying, fasting and postprandial gastric volumes by SPECT and satiation after ingestion of a nutrient drink.…”