Tradipitant achieves ‘clinically meaningful outcomes’ in gastroparesis
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Key takeaways:
- Tradipitant failed to meet statistically significant change in nausea severity at 12 weeks vs. placebo.
- Patients with high blood levels of tradipitant reported significant improvement in symptoms.
Although neurokinin-1 receptor antagonist tradipitant did not outperform placebo in improving nausea severity at 12 weeks in patients with gastroparesis, those with adequate tradipitant exposure did achieve overall symptom improvement.
“The current treatment landscape for gastroparesis is in critical need for additional solutions,” Jesse L. Carlin, PhD, clinical project lead at Vanda Pharmaceuticals, and colleagues wrote in Clinical Gastroenterology and Hepatology. “Tradipitant, a NK-1R antagonist, has demonstrated promising efficacy in improving nausea and other symptoms associated with gastroparesis. ... The results of these clinical studies further validate the NK-1 receptor as a useful target for symptom relief in diabetic and idiopathic gastroparesis.”
In a multicenter, double-blind, placebo-controlled, randomized clinical trial, researchers assessed the safety and efficacy of tradipitant among 201 adult patients with idiopathic (51.2%) or diabetic (48.8%) gastroparesis.
Patients received either tradipitant 85 mg (n = 102) or placebo (n = 99) twice daily for 12 weeks and recorded symptoms in the Gastroparesis Core Symptom Daily Diary (GCSDD). Additional patient-reported questionnaires included the Gastroparesis Cardinal Symptom Index (GCSI), Patient Global Impression of Change (PGI-C) and the Gastroparesis Treatment Benefit Survey, used to calculate Overall Patient Benefit Score (OPBS).
The primary studied endpoint was change from baseline to week 12 in average daily nausea score, as recorded in the GCSDD, while secondary outcomes included change from baseline in other symptoms of gastroparesis, nausea-free days and patient-reported outcome questionnaires.
Intention-to-treat analysis demonstrated “significant improvements from baseline” in both tradipitant and placebo groups through 12 weeks, with no significant difference between groups in nausea severity change (–1.55 vs. –1.49; P = 0.741). Both groups also reported improvements in GCSI (–1.48 vs. –1.39), PGI-C (2.46 vs. 2.59) and OPBS (1.59 vs. 1.47), but the differences were not statistically significant.
Although tradipitant was “numerically superior” in other patient-reported symptoms such as vomiting, bloating and pain, these changes did not reach statistical significance.
However, pharmacokinetic exposure-response analysis showed that participants with high blood levels of tradipitant experienced significant improvement in average nausea severity vs. placebo as early as weeks 2 to 4. This continued through week 12 but did not maintain statistical significance.
An additional post hoc analysis showed statistically significant improvement in average nausea severity for patients on tradipitant vs. placebo at week 12, as well as in overall symptoms of gastroparesis.
“Tradipitant did not meet the primary prespecified aim of this study,” Carlin and colleagues concluded. “However, three separate and supportive sub-analyses, which controlled for specific confounding factors, reveal statistically significant and clinically meaningful outcomes for gastroparesis patients treated with tradipitant.”
They continued: “Importantly, an exposure response analysis also offered additional evidence of efficacy for tradipitant. ... The effect of tradipitant in achieving improvement in nausea and improvement in overall symptoms, particularly in the first 4 to 8 weeks of treatment and when controlling for confounding factors, may suggest a disease-modifying effect.”
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