Vanda Pharmaceuticals has launched the Thetis trial to evaluate NEREUS™ (tradipitant) for preventing vomiting in patients initiating GLP-1 receptor agonist therapies, building on prior Phase 2 data showing reduced vomiting rates.
Written By: Samiksha Jadhav, BPharm
Reviewed By: Pharmacally Editorial Team
Vanda Pharmaceuticals has initiated Thetis, a clinical trial designed to evaluate NEREUS™ (tradipitant) for reducing vomiting in patients starting glucagon-like peptide-1 (GLP-1) receptor agonist therapies. NEREUS™ (tradipitant) is a neurokinin-1 (NK1) receptor antagonist licensed from Eli Lilly and Company. The therapy is approved for the acute prevention of motion-induced vomiting in adults and is also being investigated for additional indications, including gastroparesis and improving tolerability of GLP-1–based treatments.
GLP-1 receptor agonists such as semaglutide and tirzepatide are widely used for type 2 diabetes and obesity due to their meaningful metabolic and weight-loss benefits. However, gastrointestinal adverse effects remain common, particularly nausea and vomiting. These events often lead to dose adjustments or discontinuation. The issue may become more pronounced with higher-dose regimens. A recently approved higher dose of Wegovy, for example, delivered additional weight-loss benefit but reported increased frequencies of nausea and vomiting compared with the earlier maximum dose.
Mihael H. Polymeropoulos, M.D., President CEO and Chairman of the Board of Vanda Pharmaceuticals indicated that although GLP-1 therapies provide important clinical benefit, treatment-related nausea and vomiting can limit adherence and reduce quality of life. Vanda also noted that tradipitant has demonstrated antiemetic activity in prior studies, supporting further evaluation in this setting.
The Thetis trial (NCT07446439) is designed as a multicenter, randomized, double-blind, placebo-controlled study. Investigators will assess oral tradipitant in patients who begin treatment at a high dose of a GLP-1 receptor agonist. The main outcome measure is the proportion of participants who experience no vomiting episodes during the study period.
The trial follows a previously reported Phase 2 study (NCT06804603) with a comparable design. In that earlier trial, participants received tradipitant or placebo before administration of a 1 mg injection of Wegovy, a level that typically requires several weeks of dose escalation. Vomiting occurred in 29.3% of patients treated with tradipitant compared with 58.6% in the placebo arm (p=0.0016), representing a relative reduction of approximately 50%.
A key secondary endpoint evaluating vomiting accompanied by significant nausea also favored tradipitant. Such events were reported in 22.4% of participants receiving tradipitant versus 48.3% in the placebo group (p=0.0039).
Topline data from the Thetis study are anticipated in the fourth quarter of 2026. Vanda indicated that further clinical evidence may be needed after completion of this study before pursuing submission of a New Drug Application.
Reference
Vanda Pharmaceuticals Announces Initiation of The Thetis Study, a Clinical Trial of NEREUS™ for the Prevention of Vomiting Induced by GLP-1 Receptor Agonists, 08 April 2026, Vanda Pharmaceuticals Announces Initiation of The Thetis Study, a Clinical Trial of NEREUS™ for the Prevention of Vomiting Induced by GLP-1 Receptor Agonists
A Study to Measure the Effects of Using Tradipitant on Nausea and Vomiting After GLP-1R Agonist Use, ClinicalTrials.gov ID NCT06804603, https://clinicaltrials.gov/study/NCT06804603
A Study to Evaluate Tradipitant on Treating Nausea and Vomiting Induced by GLP-1R Agonist Use, ClinicalTrials.gov ID NCT07446439, https://clinicaltrials.gov/study/NCT07446439
About the Writer
Samiksha Vikram Jadhav is a B.Pharm graduate with a strong academic foundation in pharmaceutical sciences, pharmacology, and drug development. She has a keen interest in healthcare advancements, clinical research, medical writing, and emerging therapies. Her work focuses on presenting developments in the pharmaceutical and healthcare sectors through clear and accurate scientific communication.