Vanda Pharmaceuticals Inc. announced positive topline results from a randomized, controlled clinical study evaluating tradipitant, an oral NK-1 receptor antagonist, for reducing nausea and vomiting associated with Wegovy® (semaglutide) use in overweight and obese adults.
Study Design and Primary Outcome
The study (VP-VLY-686-2601) pre-treated participants with either tradipitant or placebo for one week before administering a 1 mg dose of Wegovy®, a level normally reached after nine weeks of dose escalation.
- Vomiting occurred in 29.3% of participants receiving tradipitant (17/58)
- Compared with 58.6% in the placebo group (34/58)
- p = 0.0016
This represents a 50% relative reduction, meeting the study’s primary endpoint.
Secondary Outcome
The trial also met a key secondary endpoint assessing both vomiting and significant nausea (≥3 on a 0–5 scale):
- 22.4% in the tradipitant group (13/58)
- 48.3% in the placebo group (28/58)
- p = 0.0039
Safety
Tradipitant demonstrated a safety profile consistent with previous studies, and no new safety signals were identified.
Full Endpoint Summary
|
Endpoint |
Placebo (N=58) |
Tradipitant (N=58) |
P-value |
|
Proportion with vomiting* |
58.6% (34/58) |
29.3% (17/58) |
0.0016 |
|
Proportion with vomiting + worst nausea ≥3** |
48.3% (28/58) |
22.4% (13/58) |
0.0039 |
*Primary endpoint
**Key secondary endpoint
Context and Implications
Nausea and vomiting are among the most common reasons for GLP-1 receptor agonist discontinuation, with real-world rates estimated at 30–50%. Reducing these effects could help patients continue treatment long enough to achieve meaningful weight loss and metabolic benefits.
Vanda noted that the current findings align with tradipitant’s performance in previous motion-sickness studies, where it reduced vomiting by more than 50% across multiple trials involving over 800 participants.
The global market for GLP-1 therapies exceeded $50 billion in the first three quarters of 2025.
Next Steps
The Phase II study enrolled 116 overweight or obese adults (BMI 25–40 kg/m²) with no prior GLP-1 exposure. Participants were treated for one week before and one week after receiving the single Wegovy® dose, with outcomes collected through daily patient-reported assessments.
Vanda plans to assess the regulatory pathway for tradipitant in this indication and expects to begin a Phase III program in the first half of 2026.
