Velusetrag safely improved symptoms and normalized gastric emptying in both diabetic and idiopathic gastroparesis in a phase 2b trial, the manufacturer announced.
Velusetrag (TD-5108; Theravance Biopharma) is an oral 5-hydroxytryptamine receptor 4 agonist in development for GI motility disorders. It was fast-tracked by the FDA for gastroparesis in December 2016.
The study results “demonstrate not only consistent evidence of improved gastric emptying but also meaningful improvement in gastroparesis symptoms following treatment with 5 mg of velusetrag,” Brett Haumann, MD, chief medical officer of Theravance Biopharma, said in a press release. “The findings from this study demonstrate that a 5-mg dose was sufficient to ameliorate the symptoms of gastroparesis. We believe that these findings provide clear evidence of the potential benefit of velusetrag in patients with gastroparesis, a debilitating disease in significant need of therapeutic innovation.”
In the 12-week study, investigators randomly assigned 232 patients with either diabetic or idiopathic gastroparesis to receive placebo or 5 mg, 15 mg or 30 mg of the study drug in a once daily oral dose.
“The primary endpoint analysis included a pre-specific analysis of each dose against placebo to report nominal P values. The analysis also included multiplicity adjustments of P values to account for three dose comparisons to placebo,” per the release.
At 4 weeks, those who received 5 mg velusetrag showed significant improvements in symptom scores compared with placebo based on the Gastroparesis Cardinal Symptom Index (nominal P = .0327) and the Gastroparesis Rating Scale (nominal P = .0159), the latter of which was maintained through 12 weeks (nominal P = .0427).
Moreover, patients who received the 5-mg dose also showed significant improvements in gastric emptying time (nominal P < .001) and individual disease-specific symptoms including post-prandial fullness/early satiety, bloating and upper abdominal pain (all nominal P < .05) in patients with both diabetic and idiopathic gastroparesis.
Patients who received the two higher doses of the study drug did not show significant improvements in symptoms compared with placebo, “possibly due to an increased frequency in gastrointestinal side effects at these doses that may have been caused by rapid emptying of the stomach,” according to the release. “The lack of dose response resulted in a lack of statistical significance across the three doses when adjusted for multiplicity. As a result, the statistical comparisons for the 5-mg dose are not adjusted for multiple comparisons, and all are quoted as nominal.”
The higher doses did, however, show significant improvements in gastric emptying time compared with placebo (nominal P < .001). The study drug was also generally well-tolerated, with comparable adverse event and serious adverse event rates with the 5-mg dose compared with placebo. The most common adverse events were diarrhea, nausea and headache.
The company plans to share additional data at upcoming scientific meetings and in journals, according to the press release.
“We are now preparing to meet with regulators to discuss the next phase in our development plan,” Haumann added.
Disclosures: Haumann is employed by Theravance.