Delving into the Latest Updates on TAK-906 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Trazpiroben

Target

D2 receptor x D3 receptor

Mechanism

D2 receptor antagonists(Dopamine D2 receptor antagonists), D3 receptor antagonists(Dopamine D3 receptor antagonists)

Therapeutic Areas

Nervous System DiseasesDigestive System DisordersEndocrinology and Metabolic Disease

Active Indication-

Inactive Indication

Diabetic GastroparesisGastroparesis

Originator Organization

Takeda Pharmaceutical Co., Ltd.

Active Organization-

Inactive Organization

Millennium Pharmaceuticals, Inc.

Takeda Pharmaceutical Co., Ltd.

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC31H39N3O4

InChIKeyBDXJYAAYLZTLEK-UHFFFAOYSA-N

CAS Registry1352993-39-5

The aim of this study is to understand how TAK-906 tablets and capsules are processed by the body in healthy adults under fasting conditions and also how TAK-906 tablets are processed by the body when taken with a high fat high calorie breakfast compared to fasting.
This study will require participants to stay at the clinical research unit for about 3 weeks to be monitored after receiving TAK-906.

Start Date02 Apr 2021

Sponsor / Collaborator

Takeda Pharmaceutical Co., Ltd.

NCT04454918

/ CompletedPhase 1

A Phase 1 Study to Assess Absolute Bioavailability of TAK-906 and to Characterize Mass Balance, Pharmacokinetics, Metabolism, and Excretion of [14C]-TAK-906 in Healthy Male Subjects

The purpose of this study is to determine ABA of TAK-906 following single oral (capsule) administration of 50 milligram (mg) of TAK-906 and single intravenous (IV) microtracer dose administration of 100 microgram (μg) (approximately 1 microcurie [μCi]) of [14C]-TAK-906 in Period 1 (ABA), and to determine the mass balance of TAK-906 in urine and feces following a single oral (solution) administration of 50 mg (approximately 100 μCi) of [14C]-TAK-906 in Period 2 (absorption, distribution, metabolism, and elimination [ADME]).

Start Date30 Jul 2020

Sponsor / Collaborator

Millennium Pharmaceuticals, Inc.

NCT04121078

/ CompletedPhase 1

A Phase 1, Open-Label, Randomized, Two-Way Crossover Study to Evaluate the Effect of Single-Dose Intravenous Rifampin as a Prototypic Inhibitor of OATP1B1 and OATP1B3 on the Single-Dose Pharmacokinetics of Oral TAK-906 in Healthy Adult Subjects

The purpose of this study is to evaluate the effect of single dose intravenous rifampin on the single-dose PK of orally administered TAK-906.

Start Date15 Oct 2019

Sponsor / Collaborator

Millennium Pharmaceuticals, Inc.

100 Clinical Results associated with TAK-906

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100 Translational Medicine associated with TAK-906

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100 Patents (Medical) associated with TAK-906

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10

Literatures (Medical) associated with TAK-906

01 Oct 2023·Neurogastroenterology and motility

Randomized clinical trial: A phase 2b controlled study of the efficacy and safety of trazpiroben (TAK-906) for idiopathic or diabetic gastroparesis.

Article

Author: Kuo, Braden ; Tack, Jan ; McCallum, Richard ; Chen, Yaozhu J ; Huh, Susanna Y ; Parkman, Henry P ; Mehrotra, Shailly ; Zhang, Yanwei

BACKGROUNDPrevious clinical studies of trazpiroben, a dopamine D₂ /D₃ receptor antagonist for long-term treatment of moderate-to-severe idiopathic and diabetic gastroparesis, have shown improved symptoms of fullness. This study assessed trazpiroben efficacy, safety, and tolerability in adults with idiopathic and diabetic gastroparesis versus placebo.METHODSThis global, multicenter, double-blind, parallel-group, phase 2b study (NCT03544229) enrolled eligible adults aged 18-85 years with symptomatic idiopathic or diabetic gastroparesis. Randomized participants received either oral placebo or trazpiroben 5, 25, or 50 mg, administered twice daily over 12 weeks, and completed the American Neurogastroenterology and Motility Society Gastroparesis Cardinal Symptom Index-Daily Diary. Change in weekly composite score from baseline to week 12 (primary endpoint) and treatment-emergent adverse events were assessed. Data were summarized descriptively.KEY RESULTSOverall, 242 participants were enrolled (mean [standard deviation] age 55.7 [14.2] years; 75.6% female); 193 completed the study. No significant differences in change from baseline in weekly average of the daily diary composite score occurred at week 12 between placebo (least-squares mean [standard error] -1.19 [0.12]) and trazpiroben (5, 25, and 50 mg: -1.11 [0.22], -1.17 [0.12], and -1.21 [0.12], respectively). Overall, 41.4% of participants receiving trazpiroben reported treatment-emergent adverse events (placebo, 39.7%). No serious events were considered trazpiroben-related; no life-threatening or fatal events were reported.CONCLUSIONS & INFERENCESThere was no clinically meaningful difference in efficacy between trazpiroben and placebo in treating gastroparesis, based on the primary endpoint analysis. Trazpiroben was well tolerated with no new safety concerns identified, strengthening evidence supporting its favorable safety profile. NCT number: NCT03544229.

01 Jun 2022·Clinical Pharmacology in Drug Development

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

Article

Author: Whiting, Roger ; Okamoto, Hiroyuki ; Yamaguchi, Takayoshi ; Chen, Chunlin ; Kudou, Kentarou ; Sekino, Hisakuni

AbstractTrazpiroben (TAK‐906) is a peripherally selective dopamine D2/D3 receptor antagonist being developed to treat chronic gastroparesis. This phase I, randomized, double‐blind, placebo‐controlled, single‐ and multiple‐ascending dose, parallel‐group study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of trazpiroben in healthy Japanese men. Findings were compared with those from a prior US trial in healthy individuals. Overall, 24 participants were enrolled into 3 cohorts (each n = 8). Per cohort, 6 participants received trazpiroben (cohort 1, 50 mg; 2, 100 mg; 3, 10 mg) once on day 1 and twice daily on days 3 through 7, and two received placebo. Trazpiroben was well tolerated, with no clinically meaningful adverse events observed. Following single‐ and multiple‐dose administration, trazpiroben was rapidly absorbed and eliminated (mean elimination half‐life, 1.89‐6.45 hours; median time to maximum serum concentration [steady state], 1.00‐1.25 hours). Serum prolactin increased with trazpiroben treatment (mean maximum serum concentration 93.32 ng/mL [10 mg] vs. 10.83 ng/mL [placebo]), illustrating receptor target engagement. Results reflected those from healthy US participants, indicating a lack of differences between these ethnic populations in trazpiroben disposition and safety profile. Trazpiroben may represent a promising therapy for chronic gastroparesis across different populations, with further evaluation ongoing in a phase IIb study (NCT03544229).

01 Jun 2022·Clinical and Translational ScienceQ3 · MEDICINE

The pharmacokinetics of oral trazpiroben (TAK‐906) after organic anion transporting polypeptide 1B1/1B3 inhibition: A phase I, randomized study

Q3 · MEDICINE

ArticleOA

Author: Wang, Lisi ; Dukes, George ; Tolkoff, Max ; Nishihara, Mitsuhiro ; Almansa, Cristina ; Ramsden, Diane ; Mukker, Jatinder K. ; Huh, Susanna Y. ; Chen, Chunlin

AbstractTrazpiroben is a dopamine D2/D3 receptor antagonist under development for the treatment of gastroparesis. This phase I, open‐label, randomized, two‐way crossover study (NCT04121078) evaluated the effect of single‐dose intravenous rifampin, a potent inhibitor of the organic anion transporting polypeptides (OATPs) 1B1 and 1B3, on the pharmacokinetics and safety of trazpiroben in healthy adults. The utility of coproporphyrin (CP) I and CPIII as biomarkers of OATP inhibition was also assessed. Overall, 12 participants were enrolled and randomized (1:1) into one of two treatment sequences (AB and BA). Participants received either a single oral dose of trazpiroben 25 mg (treatment A) or a single oral dose of trazpiroben 25 mg immediately after a single 30‐min intravenous infusion of rifampin 600 mg (treatment B). After a washout period of at least 7 days, participants received the other treatment. Geometric mean area under the curve from time 0 extrapolated to infinity (AUC∞) and maximum serum concentration (Cmax) of plasma trazpiroben were higher in participants receiving treatment B than those receiving treatment A (AUC∞, 168.5 vs. 32.68 ng*h/ml; Cmax, 89.62 vs. 14.37 ng/ml); corresponding geometric mean ratios (90% confidence interval) showed 5.16 (4.25–6.25) and 6.24 (4.62–8.42)‐fold increases in these parameters, respectively. In this study, trazpiroben was confirmed as a substrate of OATP1B1/1B3, and therefore co‐administration of trazpiroben with moderate to strong inhibitors of OATP1B1/1B3 is not recommended. This is also the first assessment of the utility of CPI and CPIII as endogenous biomarkers of OATP1B1/1B3 inhibition after a single intravenous dose of rifampin.

100 Deals associated with TAK-906

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Diabetic Gastroparesis	Phase 2	US	Millennium Pharmaceuticals, Inc.	26 Sep 2017
Gastroparesis	Phase 2	US	Millennium Pharmaceuticals, Inc.	26 Sep 2017

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03544229 (CTgov)	Phase 2	Gastroparesis \| Diabetic Gastroparesis	242	Placebo (Placebo)	qczhlrebtu(wtlfoaaglp) = ksmlltxvci kuhxqcitbg (uteeqhpgeg, qffaqtmgyu - sfjadtwpmx) View more	-	16 Nov 2022
				TAK-906 Maleate (TAK-906 Maleate 5 mg)	qczhlrebtu(wtlfoaaglp) = tbiniwammb kuhxqcitbg (uteeqhpgeg, wtrtawnikn - rbatvogjmo) View more
NCT04454918 (CTgov)	Phase 1	-	6	[14C]-TAK-906+TAK-906 (TAK-906 50 mg + [14C]-TAK-906 100 μg)	jraurxdirp(xfviycebsa) = voqmhzejtu imdgzmsmjq (glbufuhiss, qxhigkaeda - nsmmchvtjd) View more	-	07 Mar 2022
				[14C]-TAK-906 ([14C]-TAK-906 50 mg)	hzhlecgmbv(bcgdrncctj) = ygrmrcjxlu zqkepxfrxu (ydpuiyufzs, tcxdfqjfpg - ukrkzaoija) View more
NCT03849690 (Pubmed \| Clin Transl Sci)	Phase 1	-	12	Trazpiroben 25 mg alone	qbldkvyhup(cteyicggog) = idktftgevw yklsjfdayf (syixhikmdl ) View more	Positive	26 Feb 2022
				Trazpiroben 25 mg + Esomeprazole 40 mg	qbldkvyhup(cteyicggog) = gsismknjgk yklsjfdayf (syixhikmdl ) View more
NCT03544229 (Pubmed)	Phase 1	-	24	Trazpiroben	sqnviyrfce(dkprcsjfba) = Trazpiroben was well tolerated, with no clinically meaningful adverse events observed tvwjftdjrg (evwdkgioja )	-	29 Dec 2021
				Placebo
NCT03849690 (CTgov)	Phase 1	-	12	TAK-906 (TAK-906 25 mg)	kvqfrrvxuu(tcvhrznqlf) = oejjcaowng fknfgvaimg (urtvmeeebl, jbfaduvxdm - oiziqhklno) View more	-	12 May 2020
				Esomeprazole+TAK-906 (Esomeprazole 40 mg and TAK-906 25 mg)	kvqfrrvxuu(tcvhrznqlf) = ujwvqxvffg fknfgvaimg (urtvmeeebl, tuaoknacxt - ihelrfzqha) View more
NCT03268941 (CTgov)	Phase 2	Gastroparesis \| Diabetic Gastroparesis	51	TAK-906 Maleate Placebo (Part 1: Placebo)	(fmjoibkvxp) = qhedkmaruk vjvfaujlhm (brrblxsfnb, iolwdfeiym - yrhpslfhsu) View more	-	23 Jul 2019
				TAK-906 Maleate (Part 1: TAK 906 Maleate 5 mg)	(fmjoibkvxp) = ozduzmhsdt vjvfaujlhm (brrblxsfnb, ygcrfcypoi - mfbatikdmw) View more
NCT03237156 (CTgov)	Phase 1	-	24	placebo+TAK-906 (Cohorts 1-3: Placebo)	xqjlzccryg(wdienimoic) = mtxueyejpv ycnspatpjm (ssdezfhnly, xggsuivhgu - gledamvbkr) View more	-	18 Feb 2019
				TAK-906 (Cohort 1: TAK-906 50 mg)	xqjlzccryg(wdienimoic) = xihbmldpzu ycnspatpjm (ssdezfhnly, snfjiizwgf - gqjyvaawin) View more
UEGW2018	Not Applicable	-	-	TAK-906 25 mg alone	(buyxgfqqgi) = There were no AEs in period 1 nybgacrctt (knrfzpzuql ) View more	-	01 Oct 2018
				TAK-906 25 mg with itraconazole 200 mg