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TAK-954

Phase 2

Diabetic Gastroparesis | Small molecule | Gastrointestinal |Takeda Pharmaceutical Company Limited|Last Updated: Jun 23, 2023

Success Probability

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Market & Valuation

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Trial Design

RandomizedDouble-BlindPLACEBO_CONTROLLED
Total Trials1
Total Enrollment36

FDA Designations

No designations recorded

Clinical trial landscape

TAK-954 · 7 trials · 7 indications

Phase 2 2Phase 1 5
NCT03827655A Study of TAK-954 to Treat Gastrointestinal Dysfunction in Adults After SurgeryPostoperative Gastrointestinal Dysfunction
COMPLETED209 Analytics
NCT03281577Effect of TAK-954 on Gastrointestinal and Colonic Transit in Diabetic or Idiopathic Gastroparesis ParticipantsDiabetic Gastroparesis
COMPLETED36 Analytics
PHASE2COMPLETED
A Study of TAK-954 to Treat Gastrointestinal Dysfunction in Adults After Surgery
Postoperative Gastrointestinal DysfunctionUnlock trial analytics
PHASE2COMPLETED
Effect of TAK-954 on Gastrointestinal and Colonic Transit in Diabetic or Idiopathic Gastroparesis Participants
Diabetic GastroparesisUnlock trial analytics

Study Endpoints

Primary Endpoints

Time From End of the Surgery to Resolution of Upper and Lower Gastrointestinal (GI) Function Postsurgery as Assessed by the Investigator
Day 1 (surgery) up to Day 10 postsurgery

The time from end of surgery to tolerance of solid food, without first occurrence of vomiting or clinically significant nausea for 1 calendar day after a solid meal (upper GI function) and first spontaneous bowel movement (lower GI function), whichever occurred later up to 10 days postsurgery was observed. Kaplan-Meier survival analysis method was used.

Percent Change From Baseline in Half-emptying Time (T1/2) of Gastric Solids
Predose and at multiple time-points post-dose (up to 9 hours) on Day 2

Half-emptying time (t1/2) of gastric solids is the time for half of the ingested solids or liquids to leave the stomach. Scintigraphy assessments were used to evaluate the gastric emptying of solids following a radio-labelled meal. A negative percent change from baseline indicated improvement.

Cumulative Percentage of Administered Radioactivity Recovered in Urine
Day 1 pre-dose and at multiple time points (up to 264, 312, and 336 hours) post-dose
Cumulative Percentage of Administered Radioactivity Recovered in Feces
Day 1 pre-dose and at multiple time points (up to 264, 312, and 336 hours) post-dose
Cumulative Percentage of Radioactivity in Urine and Feces Combined
Day 1 pre-dose and at multiple time points (up to 264, 312, and 336 hours) post-dose
Normalized Recovery as Percentage of Dose for TAK-954 and TAK-954 Metabolites in Urine and Feces Combined
Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose

Percentage of dose recovered for TAK-954 and its metabolites derived from 0-168 hour sampling was normalized for 100% recovery.

Normalized Recovery as Percentage of Dose for TAK-954 and TAK-954 Metabolites in Urine
Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose

Percentage of dose recovered for TAK-954 and its metabolites derived from 0-168 hour sampling was normalized for 100% recovery.

Normalized Recovery as Percentage of Dose for TAK-954 and TAK-954 Metabolites in Feces
Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose

Percentage of dose recovered for TAK-954 and its metabolites derived from 0-168 hour sampling was normalized for 100% recovery.

Mean Percent of Total Radioactivity in Plasma for TAK-954 and TAK-954 Metabolites
Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Cumulative Percentage of Dose Excreted in Urine for TAK-954
Day 1 pre-dose and at multiple time points (up to 264, 312, and 336 hours) post-dose
Cumulative Percentage of Dose Excreted in Feces for TAK-954
Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose

The cumulative percentage of dose excreted in feces as TAK-954 derived from 0-168 hour sampling was normalized for 100% recovery.

Mean Concentration of Total Radioactivity in Whole Blood and Plasma [14C]-TAK-954
Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
Cmax: Maximum Observed Plasma and Whole Blood Concentrations of Radioactivity for [14C]-TAK-954
Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
Cmax: Maximum Observed Plasma Concentration for TAK-954 and TAK-954 Metabolites
Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
AUClast: Area Under the Plasma and Whole Blood Radioactivity-time Curve From Time 0 to the Time of the Last Quantifiable Radioactivity for [14C]-TAK-954
Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-954 and TAK-954 Metabolites
Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
AUC∞: Area Under the Plasma and Whole Blood Radioactivity-time Curve From Time 0 to Infinity for [14C]-TAK-954
Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-954 and TAK-954 Metabolites
Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
Tmax: Time to Reach the Maximum Plasma and Whole Blood Radioactivity for [14C]-TAK-954
Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-954 and TAK-954 Metabolites
Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
t1/2z: Terminal Disposition Phase Half-life of Radioactivity in Plasma and Whole Blood for [14C]-TAK-954
Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
t1/2z: Terminal Disposition Phase Half-life in Plasma for TAK-954 and TAK-954 Metabolites
Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
CL: Total Clearance After Intravenous Administration for [14C]-TAK-954
Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
CL: Total Clearance of TAK-954 After Intravenous Administration of [14C]-TAK-954
Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
Vz: Volume of Distribution During the Terminal Disposition Phase After Intravenous Administration for [14C]-TAK-954
Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
Vz: Volume of Distribution During the Terminal Disposition Phase After Intravenous Administration for TAK-954
Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
Aet Urine: Amount of Total Radioactivity Excreted in Urine From Time 0 to Time t for [14C]-TAK-954
Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
Aet Urine: Amount of Drug Excreted in Urine From Time 0 to Time t for TAK-954
Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
Aet Feces: Amount of Total Radioactivity Excreted in Feces From Time 0 to Time t for [14C]-TAK-954
Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
Fet Urine: Fraction of Drug Excreted in Urine From Time 0 to Time t for TAK-954
Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
Fet Urine: Fraction of Total Radioactivity Excreted in Urine From Time 0 to Time t for [14C]-TAK-954
Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
Fet Feces: Fraction of Radioactivity Excreted in Feces From Time 0 to Time t for [14C]-TAK-954
Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) for TAK-954
Dosing on Day 2 in Period 1 up to 14 days after last dose of study drug on Day 2 of Period 3 (up to Day 52)
Number of Participants With Clinically Significant Change From Baseline in Vital Signs for TAK-954
Dosing on Day 2 in Period 1 up to 14 days after last dose of study drug on Day 2 of Period 3 (up to Day 52)
Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiograms (ECG) for TAK-954
Dosing on Day 2 in Period 1 up to 14 days after last dose of study drug on Day 2 of Period 3 (up to Day 52)
Number of Participants With Clinically Notable Shifts From Baseline to Abnormal Post-dose in Clinical Laboratory Values for TAK-954
Dosing on Day 2 in Period 1 up to 14 days after last dose of study drug on Day 2 of Period 3 (up to Day 52)
AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-954
Day 2 pre-dose and at multiple time points (up to 336 hours) post-dose
AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-954
Day 2 pre-dose and at multiple time points (up to 336 hours) post-dose
Ceoi: Plasma Concentration Observed at the End of Infusion for TAK-954
Day 2 pre-dose and at multiple time points (up to 336 hours) post-dose
CL: Total Clearance After Intravenous Administration for TAK-954
Day 2 pre-dose and at multiple time points (up to 336 hours) post-dose
Ae: Amount of Unchanged Drug Excreted in the Urine for TAK-954 on Day 2 up to 12 Hours Post-dose
Day 2 pre-dose and at multiple time points (up to 12 hours) post-dose
Ae: Amount of Unchanged Drug Excreted in the Urine for TAK-954 on Day 2 up to 24 Hours Post-dose
Day 2 pre-dose and at multiple time points (up to 24 hours) post-dose
Ae: Amount of Unchanged Drug Excreted in the Urine for TAK-954 on Day 2 up to 36 Hours Post-dose
Day 2 pre-dose and at multiple time points (up to 36 hours) post-dose
Fe: Fraction of TAK-954 Excreted in Urine on Day 2 up to 12 Hours Post-dose
Day 2 pre-dose and at multiple time points (up to 12 hours) post-dose
Fe: Fraction of TAK-954 Excreted in Urine on Day 2 up to 24 Hours Post-dose
Day 2 pre-dose and at multiple time points (up to 24 hours) post-dose
Fe: Fraction of TAK-954 Excreted in Urine on Day 2 up to 36 Hours Post-dose
Day 2 pre-dose and at multiple time points (up to 36 hours) post-dose
CLR: Renal Clearance for TAK-954
Day 2 pre-dose and at multiple time points (up to 36 hours) post-dose
Groups A, C and D; Cmax: Maximum Observed Plasma Concentration for TAK-954 (Total and Free)
Day 1 pre-infusion and at multiple time points (up to 120 hours) post-infusion
Groups A, C and D; AUC(0-72): Area Under the Plasma Concentration-time Curve From Time 0 to 72 Hours Post-dose for TAK-954 (Free and Total)
Day 1 pre-infusion and at multiple time points (up to 72 hours) post-infusion
Groups A, C and D; AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-954 (Free and Total)
Day 1 pre-infusion and at multiple time points (up to 120 hours) post-infusion
Groups A, C and D; AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-954 (Free and Total)
Day 1 pre-infusion and at multiple time points (up to 120 hours) post-infusion
Groups A, C and D; Ae: Amount of TAK-954 Excreted in Urine
Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion
Group E; Ae: Amount of TAK-954 Excreted in Urine in Period 1
Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion
Group E; Ae: Amount of TAK-954 Excreted in Urine in Period 2
Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion
Groups A, C and D; Fe: Fraction of TAK-954 Excreted in Urine
Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion
Group E; Fe: Fraction of TAK-954 Excreted in Urine in Period 1
Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion
Group E; Fe: Fraction of TAK-954 Excreted in Urine in Period 2
Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion
Groups A, C and D; CLR: Renal Clearance for TAK-954
Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion
Group E; CLR: Renal Clearance for TAK-954 in Period 1
Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion
Group E; CLR: Renal Clearance for TAK-954 in Period 2
Day 1 pre-infusion and at multiple time points (up to 24 hours) post-infusion
Group E; CLD: Clearance of Dialysate for TAK-954 in Period 2
Day 1 pre-infusion and at multiple time points (up to 4 hours) post-infusion
Cmax: Maximum Observed Plasma Concentration for TAK-954 (Total and Free)
Day 1 pre-infusion and at multiple time points (up to 96 hours) post-infusion
AUClast: Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-954 (Total and Free)
Day 1 pre-infusion and at multiple time points (up to 96 hours) post-infusion
AUC∞: Area Under the Concentration-time Curve From Time 0 to Infinity for TAK-954 (Total and Free)
Day 1 pre-infusion and at multiple time points (up to 96 hours) post-infusion
Cmax: Maximum Observed Plasma Concentration for TAK-954
TAK-954 0.2 mg: Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose; Itraconazole 200 mg and TAK-954 0.2 mg: Day 4 pre-dose and at multiple time points (up to 120 hours) post-dose

Secondary Endpoints

Time From the End of the Surgery (Time the Incision is Closed) Until Ready for Discharge as Assessed by the Investigator
Day 1 (surgery) up to Day 24
Time From the End of Surgery Until the Discharge Order is Written
Day 1 (surgery) up to Day 24
Time From the End of Surgery to Discharge From Hospital
Day 1 (surgery) up to Day 24
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Study Design & Arms

AllocationRANDOMIZED
MaskingQUADRUPLE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
PlaceboPLACEBO_COMPARATORTAK-954 placebo-matching, 60-minute infusion, intravenously (IV), once presurgery on Day 1 and once daily postsurgery until return of upper and lower GI function or for up to 10 days.
TAK-954 0.1 mg/100 mLEXPERIMENTALTAK-954 0.1 milligrams per 100 milliliters (mg/100 mL), 60-minute infusion, IV, once presurgery on Day 1 and once daily postsurgery until return of upper and lower GI function or for up to 10 days.
TAK-954 0.5 mg/100 mLEXPERIMENTALTAK-954 0.5 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily postsurgery until return of upper and lower GI function or for up to 10 days.
TAK-954 0.1 mg/100 mL + PlaceboEXPERIMENTALTAK-954 0.1 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily placebo infusions postsurgery up to Day 10 or until resolution of upper and lower GI function.
TAK-954 0.5 mg/100 mL + PlaceboEXPERIMENTALTAK-954 0.5 mg/100 mL, 60-minute infusion, IV, once presurgery on Day 1 and once daily placebo infusions postsurgery up to Day 10 or until resolution of upper and lower GI function.
TAK-954 0.1 mgEXPERIMENTALTAK-954 0.1 mg, 60-minute infusion, IV, once daily on Days 1 to 3.
TAK-954 0.3 mgEXPERIMENTALTAK-954 1 mg, 60-minute infusion, IV, once daily for up to 3 days.
TAK-954 1 mgEXPERIMENTALTAK-954 1 mg, 60-minute infusion, IV, once daily on Days 1 to 3.
[14C]-TAK-954 0.5 mgEXPERIMENTAL\[14C\]-TAK-954 0.5 milligram (mg), (containing approximately 1.5 microcurie \[µCi\] of radioactive tracer), administered as 60-minute infusion, intravenously, once on Day 1.
Sequence 1EXPERIMENTALPeriod 1: TAK-954 placebo-matching infusion, administered intravenously over 60-minutes, once on Day 1 and Day 2. Period 2: TAK-954 0.1 milligram (mg), infusion, administered intravenously over 60-minutes, once on Day 1, TAK-954 1 mg infusion, administered intravenously over 60-minutes, once on Day 2. Period 3: TAK-954 0.1 mg, infusion, administered intravenously over 60-minutes, once on Day 1, TAK-954 2 mg infusion, administered intravenously over 60-minutes, once on Day 2. A washout period of at least 16 days will be maintained between each Treatment Period.
Sequence 2EXPERIMENTALPeriod 1: TAK-954 0.1 mg, infusion, administered intravenously over 60-minutes, once on Day 1, TAK-954 0.5 mg infusion, administered intravenously over 60-minutes once on Day 2. Period 2: TAK-954 placebo-matching infusion, administered intravenously over 60-minutes, once on Day 1 and Day 2. Period 3: TAK-954 0.1 mg, infusion, administered intravenously over 60-minutes, once on Day 1, TAK-954 2 mg, infusion, administered intravenously over 60-minutes, once on Day 2. A washout period of at least 16 days will be maintained between each Treatment Period.
Sequence 3EXPERIMENTALPeriod 1: TAK-954 0.1 mg, infusion, administered intravenously over 60-minutes, once on Day 1, TAK-954 0.5 mg, infusion, administered intravenously over 60-minutes once on Day 2. Period 2: TAK-954 0.1 mg, infusion, administered intravenously over 60-minutes, once on Day 1, TAK-954 1 mg, infusion, administered intravenously over 60-minutes, once on Day 2. Period 3: TAK-954 placebo-matching infusion, administered intravenously over 60-minutes, once on Day 1 and Day 2. A washout period of at least 16 days will be maintained between each Treatment Period.
Group A TAK-954 0.2 mg: Healthy ParticipantsEXPERIMENTALParticipants with normal renal function receive TAK-954 0.2 milligram (mg), infusion, intravenously in fasted state, once on Day 1 of a 6-day period.
Group B TAK-954 0.2 mg: Mild Renal ImpairmentEXPERIMENTALParticipants receive TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 6-day period.
Group C TAK-954 0.2 mg: Moderate Renal ImpairmentEXPERIMENTALParticipants receive TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 6-day period.
Group D TAK-954 0.2 mg: Severe Renal ImpairmentEXPERIMENTALParticipants without hemodialysis or End-stage Renal Disease (ESRD) receive TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 6-day period.
Group E TAK-954 0.2 mg: End-stage Renal Disease (ESRD)EXPERIMENTALParticipants with hemodialysis receive TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 4-day period followed by a minimum 13-day washout period, further followed by TAK-954 0.2 mg, infusion, intravenously in fasted state, once on Day 1 of a 4-day period.
Group 1 Mild Hepatic Impairment: TAK-954 0.2 mgEXPERIMENTALTAK-954 0.2 milligram (mg), intravenous, administered as 60-minute infusion, once on Day 1.
Group 2 Moderate Hepatic Impairment: TAK-954 0.2 mgEXPERIMENTALTAK-954 0.2 mg, intravenous, administered as 60-minute infusion, once on Day 1.
Group 3 Severe Hepatic Impairment: TAK-954 0.2 mgEXPERIMENTALTAK-954 0.2 mg, intravenous, administered as 60-minute infusion, once on Day 1.
Group 4 Healthy Participants: TAK-954 0.2 mgEXPERIMENTALTAK-954 0.2 mg, intravenous, administered as 60-minute infusion, once on Day 1.
TAK-954 0.2 mg + Itraconazole 200 mg and TAK-954 0.2mgEXPERIMENTALTAK-954 0.2 milligram (mg), infusion, intravenously, once on Day 1 of First Intervention Period, followed by a minimum of 7-day washout period, further followed by Itraconazole 200 mg, capsule, orally, once daily on Days 1 to 8 along with TAK-954 0.2 mg, infusion, intravenously on Day 4 of Second Intervention Period.

Interventions

NameTypeDescription
TAK-954 PlaceboDRUGTAK-954 placebo-matching intravenous infusion.
TAK-954DRUGTAK-954 intravenous infusion.
PlaceboDRUGTAK-954 placebo-matching IV infusion.
[14C]-TAK-954DRUG\[14C\]-TAK-954 intravenous infusion.
ItraconazoleDRUGItraconazole Capsule
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Eligibility Criteria

Age Range18 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites25

Inclusion Criteria: 1. Participant is scheduled to undergo a laparoscopic-assisted or open partial small- or large-bowel resection. 2. Participant's American Society of Anesthesiologists (ASA) physical status classification is ASA 1 to 3. Exclusion Criteria: 1. Has significant mechanical bowel ob...

Countries:United StatesGermanyNetherlandsCzechiaHungarySlovakia
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Frequently asked questions about TAK-954

What is TAK-954 used for?

TAK-954 is an investigational small molecule being studied for gastrointestinal conditions, including diabetic gastroparesis, idiopathic gastroparesis, and postoperative gastrointestinal dysfunction. It has also been evaluated in healthy volunteers and in people with renal or hepatic impairment to assess how the body processes the drug.

Who is developing TAK-954?

TAK-954 is being developed by Takeda Pharmaceutical Company Limited, which trades on the New York Stock Exchange under the ticker TAK. Takeda is conducting clinical trials of TAK-954 across multiple countries, including the United States, Czechia, Hungary, and the Netherlands.

What phase is TAK-954 in?

TAK-954 is in Phase 2 clinical development. A Phase 2 trial in diabetic or idiopathic gastroparesis has been completed, along with several Phase 1 studies in healthy volunteers and in people with renal impairment. The drug is investigational and has not been approved by regulatory authorities.

What clinical trials is TAK-954 in?

TAK-954 has completed four clinical trials. NCT03281577 was a Phase 2 study in diabetic or idiopathic gastroparesis. NCT03296787 evaluated renal impairment and dialysis effects. NCT03500224 studied mass balance and metabolism in healthy males, and NCT03870555 investigated safety and tolerability in healthy adults.

Is TAK-954 the same as another drug?

TAK-954 is the primary name used in clinical trial records for this investigational compound. No alternative names have been associated with TAK-954 in the available trial information, so it is not known to be the same as any other marketed or investigational drug.