Trazpiroben

Trazpiroben
Clinical data
Other namesTAK-906; ATC-1906
Drug classDopamine antagonist
Identifiers
  • 3-[[1-cyclohexyl-4-oxo-8-(4-oxo-4-phenylbutyl)-1,3,8-triazaspiro[4.5]decan-3-yl]methyl]benzoic acid
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
Chemical and physical data
FormulaC31H39N3O4
Molar mass517.670 g·mol−1
3D model (JSmol)
  • C1CCC(CC1)N2CN(C(=O)C23CCN(CC3)CCCC(=O)C4=CC=CC=C4)CC5=CC(=CC=C5)C(=O)O
  • InChI=1S/C31H39N3O4/c35-28(25-10-3-1-4-11-25)15-8-18-32-19-16-31(17-20-32)30(38)33(23-34(31)27-13-5-2-6-14-27)22-24-9-7-12-26(21-24)29(36)37/h1,3-4,7,9-12,21,27H,2,5-6,8,13-20,22-23H2,(H,36,37)
  • Key:BDXJYAAYLZTLEK-UHFFFAOYSA-N

Trazpiroben (developmental code name TAK-906) is a dopamine antagonist drug which was under development for the treatment of gastroparesis. It acts as a peripherally selective dopamine D2 and D3 receptor antagonist. The drug has been found to strongly increase prolactin levels in humans, similarly to other peripherally selective D2 receptor antagonists like domperidone. Clinical development of trazpiroben was discontinued before April 2022. Trazpiroben was originated by Altos Therapeutics and was under development by Takeda Oncology.

In a global phase 2b trial (NCT03544229), adults aged 18 to 85 with idiopathic or diabetic gastroparesis received oral trazpiroben 5, 25 or 50 mg, or placebo, twice daily for 12 weeks.[N1] The primary endpoint analysis found no clinically meaningful difference in efficacy between trazpiroben and placebo. The drug was well tolerated: 41.4% of participants receiving trazpiroben reported treatment-emergent adverse events, compared with 39.7% on placebo, and no serious events were considered drug-related.[N1] Prolactin levels rose in the 25 mg and 50 mg groups, consistent with the drug’s mechanism of action.[N2]

Takeda discontinued clinical development of trazpiroben in early 2022 in response to the phase 2b data.[1][N3] Trazpiroben was originated by Altos Therapeutics and was under development by Takeda

References

  1. 1 2 3 4 "Trazpiroben - Takeda Oncology - AdisInsight".
  2. 1 2 Whiting RL, Choppin A, Luehr G, Jasper JR (October 2021). "Preclinical Evaluation of the Effects of Trazpiroben (TAK-906), a Novel, Potent Dopamine D2/D3 Receptor Antagonist for the Management of Gastroparesis". J Pharmacol Exp Ther. 379 (1): 85–95. doi:10.1124/jpet.121.000698. PMID 34253646. S2CID 235809216.
  3. ↑ Whiting RL, Darpo B, Chen C, Fletcher M, Combs D, Xue H, Stoltz RR (August 2021). "Safety, Pharmacokinetics, and Pharmacodynamics of Trazpiroben (TAK-906), a Novel Selective D2 /D3 Receptor Antagonist: A Phase 1 Randomized, Placebo-Controlled Single- and Multiple-Dose Escalation Study in Healthy Participants". Clin Pharmacol Drug Dev. 10 (8): 927–939. doi:10.1002/cpdd.906. PMC 8451790. PMID 33462988.
  4. ↑ Kuo B, Scimia C, Dukes G, Zhang W, Gupta S, Chen C, Chuang E, Camilleri M (August 2021). "Randomised clinical trial: safety, pharmacokinetics and pharmacodynamics of trazpiroben (TAK-906), a dopamine D2 /D3 receptor antagonist, in patients with gastroparesis". Aliment Pharmacol Ther. 54 (3): 267–280. doi:10.1111/apt.16451. PMID 34148244. S2CID 235492049.
  5. 1 2 Yamaguchi T, Kudou K, Okamoto H, Chen C, Whiting R, Sekino H (December 2021). "Evaluating the Safety, Tolerability, and Disposition of Trazpiroben, a D2 /D3 Receptor Antagonist: Phase I Single- and Multiple-Ascending Dose Studies in Healthy Japanese Participants". Clin Pharmacol Drug Dev. 11 (6): 695–706. doi:10.1002/cpdd.1057. PMC 9303893. PMID 34967147. S2CID 245567576.