Trazpiroben shows promise in treatment of gastroparesis, claims study

Gastroparesis is a chronic gastric motility disorder. Dopamine D2/D3 receptor antagonists metoclopramide and domperidone are current treatment options but are associated with central nervous system and cardiovascular safety concerns, respectively, precluding chronic use. It is well established that dopamine D2/D3 receptor antagonists can reduce the symptoms of gastroparesis. Dopamine antagonists are effective in the establishment of normal gastric myoelectric activity and resolution of gastric dysrhythmias, which are reported to have a more direct relationship to the improvement of symptoms in patients with gastroparesis than gastric emptying alone. Furthermore, dopamine receptor antagonists have a direct antiemetic effect via inhibition of dopamine receptors in the chemoreceptor trigger zone.

Trazpiroben (TAK-906), a dopamine D2/D3 receptor antagonist, is under development for chronic treatment of moderate-to-severe gastroparesis. Nonclinical data suggest trazpiroben will have D2/D3 receptor antagonism comparable with metoclopramide or domperidone.

So, researchers aimed to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics (effect on prolactin and gastric function) of twice-daily trazpiroben (5, 25 and 100 mg) in participants with gastroparesis.

This phase 2a pilot study evaluated gastric emptying using the gastric emptying breath test, with metoclopramide as an internal control. Gastric accommodation and gastroparesis symptoms were assessed using the nutrient drink test and American Neurogastroenterology and Motility Society Gastroparesis Cardinal Symptom Index-Daily Diary, respectively.

Results revealed some new facts.

• Overall, 51 participants were enrolled. Trazpiroben was well tolerated, demonstrating a favourable safety profile without cardiovascular or central nervous system adverse events.
• All trazpiroben doses were rapidly absorbed and eliminated (t1/2z 4-5 hours), and D2/D3 receptor target engagement confirmed by increased serum prolactin (peaking at trazpiroben 25 mg).
• No effect on gastric emptying was demonstrated with trazpiroben or metoclopramide (P > 0.05), although benefits in volume-to-fullness were seen at trazpiroben 5 mg (P > 0.05) and 25 mg (88.5 vs −26.3 mL; P = 0.019), and nonsignificant numerical aggregate symptom score improvements were observed with trazpiroben 25 mg vs placebo (P = 0.182).

For full article follow the link: https://doi.org/10.1111/apt.16451

Source: Alimentary Pharmacology & Therapeutics