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Effect of TAK-954 on Gastrointestinal and Colonic Transit in Diabetic or Idiopathic Gastroparesis Participants

Primary Purpose

Diabetic Gastroparesis, Idiopathic Gastroparesis

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

TAK-954

Placebo

About this trial

This is an interventional treatment trial for Diabetic Gastroparesis focused on measuring Drug Therapy

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Has diabetes mellitus with symptoms of gastroparesis and previously documented gastric emptying delay or previously documented idiopathic gastroparesis in the last 5 years.
Has a body mass index (BMI) greater than or equal to (>=) 16 and less than or equal to (<=) 40 kilogram per square meter (kg/m^2) at the Screening Visit.

Exclusion Criteria:

Has glycosylated hemoglobin (HbA1c) greater than (>) 12 percent (%).
Has other structural diseases/conditions that affect the gastrointestinal (GI) system.
Are unable to withdraw drugs known to alter GI transit 48 hours prior to the study.
Has clinically significant abnormal baseline safety laboratory values.
Has preexisting hepatic disease that meets Child-Pugh Class B (moderate; total score 7 to 9 points) or C (severe; total score 10 to 15 points).
Are without known preexisting hepatic disease who have 1 or more of the following:
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2 times the upper limit of normal (ULN).
- Bilirubin >1.5 times the ULN unless due to Gilbert's syndrome.
- International normalized ratio (INR) >1.5 unless on anticoagulation therapy.
Has QT intervals with Fridericia correction method (QTcF) interval (>=) 460 millisecond (msec) or with other factors that increase the risk of QT prolongation or arrhythmic events at screening. Note: Participants with bundle branch block and a prolonged QTc interval, or with QTcF between 450 and 460 msec, should be reviewed by the Medical Monitor for potential inclusion.
Has second or third degree atrioventricular (AV) block; AV disassociation; >5 beats of non-sustained VT at a rate >120 beats per minute (bpm); Electrocardiogram (ECG) changes consistent with acute myocardial ischemia or infarction.
Has cardiac history that includes conditions requiring heart rate control (example, atrial fibrillation, atrial flutter, ventricular tachycardia, or other tachyarrhythmias).
Has clinical evidence (including physical examination, ECG, clinical laboratory value and review of the medical history) of significant cardiovascular, respiratory, moderate or severe renal insufficiency (creatinine clearance <=60 mL/min), hematological, neurological, or psychiatric disease, or other disease that interferes with the objectives of the study.
If female, are pregnant or lactating or intending to become pregnant before participating in this study, during the study, and 4 to 5 days (5 half-lives) PLUS 30 days after last dose of the study drug; or intending to donate ova during such time period.
Are considered by the investigator to be alcoholics not in remission or known substance abusers. Have a history of alcohol consumption exceeding 2 standard drinks per day on average (1 glass is approximately equivalent to: beer [354 milliliter per [mL/] 12 ounces], wine [118 mL/4 ounces], or distilled spirits [29.5 mL/1 ounce] per day).

Sites / Locations

Mayo Clinic

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo

TAK-954 0.1 mg

TAK-954 0.3 mg

TAK-954 1 mg

Arm Description

TAK-954 placebo-matching, 60-minute infusion, intravenously (IV), once daily on Days 1 to 3.

TAK-954 0.1 mg, 60-minute infusion, IV, once daily on Days 1 to 3.

TAK-954 1 mg, 60-minute infusion, IV, once daily for up to 3 days.

TAK-954 1 mg, 60-minute infusion, IV, once daily on Days 1 to 3.

Outcomes

Primary Outcome Measures

Percent Change From Baseline in Half-emptying Time (T1/2) of Gastric Solids

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.

Secondary Outcome Measures

Colonic Geometric Center

The scintigraphic method was used to measure colonic geometric center following a radio-labelled meal. The geometric center (GC) was the weighted average of counts in the different colonic regions, where 0= no radioactivity in the colon and if radioactivity was detected in the colon, 1=all isotope was in the ascending colon and 5=all isotope was in the stool; a high GC indicated faster colonic transit.

Colonic Filling at Hour 6

Colonic filling was estimated as percentage of the radio-labelled meal that reached the colon at Hour 6.

Half-emptying Time (T1/2) of Ascending Colon

T1/2 of ascending colon emptying was estimated by analysis of proportionate emptying over time of counts from the colon. Scintigraphy assessments were used to evaluate the emptying of solids or liquids from ascending colon following a radio-labelled meal.

AUCtau: Area Under the Plasma Concentration-Time Curve From Time 0 to t for TAK-954

Cmax: Maximum Observed Plasma Concentration for TAK-954

Ctrough: Observed Plasma Concentration at the End of a Dosing Interval

Full Information

NCT ID

NCT03281577

First Posted

September 11, 2017

Last Updated

December 16, 2020

Sponsor

Takeda

1. Study Identification

Unique Protocol Identification Number

NCT03281577

Brief Title

Effect of TAK-954 on Gastrointestinal and Colonic Transit in Diabetic or Idiopathic Gastroparesis Participants

Official Title

A Dose-Ranging, Randomized, Parallel, Placebo-Controlled Study to Assess the Effect of TAK-954 on Gastrointestinal and Colonic Transit in Patients With Diabetic or Idiopathic Gastroparesis

Study Type

Interventional

2. Study Status

Record Verification Date

December 2020

Overall Recruitment Status

Completed

Study Start Date

January 2, 2018 (Actual)

Primary Completion Date

June 7, 2019 (Actual)

Study Completion Date

July 12, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Takeda

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief Summary

The purpose of this study is to evaluate the dose-dependent effects of TAK-954 on gastric emptying time of solids in participants with diabetic or idiopathic gastroparesis assessed by scintigraphy.

Detailed Description

The drug being tested in this study is called TAK-954. TAK-954 is a serotonin (5 HT4) receptor agonist and is being tested to treat people who have diabetic or idiopathic gastroparesis and who previously reported delay in stomach emptying. This study will look at the gastric emptying time of solids in people who take TAK-954 or placebo. The study will enroll approximately 41 patients. Participants will be randomly assigned (by chance, like flipping a coin) to one of the four treatment groups-which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need): TAK-954 0.1 mg TAK-954 0.3 mg TAK-954 1 mg Placebo (dummy inactive solution) - this is a solution that looks like the study drug but has no active ingredient. This single center trial will be conducted in the United States. The duration of treatment is 3 days and the overall period of evaluation is up to 28 days. The participants will be contacted by telephone (Days 10 to 14) for follow-up assessment. There will be another follow-up phone call for women of childbearing potential (Days 38 to 43).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Diabetic Gastroparesis, Idiopathic Gastroparesis

Keywords

Drug Therapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

36 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

TAK-954 placebo-matching, 60-minute infusion, intravenously (IV), once daily on Days 1 to 3.

Arm Title

TAK-954 0.1 mg

Arm Type

Experimental

Arm Description

TAK-954 0.1 mg, 60-minute infusion, IV, once daily on Days 1 to 3.

Arm Title

TAK-954 0.3 mg

Arm Type

Experimental

Arm Description

TAK-954 1 mg, 60-minute infusion, IV, once daily for up to 3 days.

Arm Title

TAK-954 1 mg

Arm Type

Experimental

Arm Description

TAK-954 1 mg, 60-minute infusion, IV, once daily on Days 1 to 3.

Intervention Type

Drug

Intervention Name(s)

TAK-954

Intervention Description

TAK-954 IV infusion.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

TAK-954 placebo-matching IV infusion.

Primary Outcome Measure Information:

Title

Percent Change From Baseline in Half-emptying Time (T1/2) of Gastric Solids

Description

Time Frame

Predose and at multiple time-points post-dose (up to 9 hours) on Day 2

Secondary Outcome Measure Information:

Title

Colonic Geometric Center

Description

Time Frame

4, 24, and 48 hours post-radiolabeled meal on Day 2

Title

Colonic Filling at Hour 6

Description

Colonic filling was estimated as percentage of the radio-labelled meal that reached the colon at Hour 6.

Time Frame

6 hours post-radiolabel meal on Day 2

Title

Half-emptying Time (T1/2) of Ascending Colon

Description

Time Frame

Predose and at multiple time-points post-dose (up to 25 hours) on Days 1, 2 and 3

Title

AUCtau: Area Under the Plasma Concentration-Time Curve From Time 0 to t for TAK-954

Time Frame

Predose and at multiple time-points post-dose (up to 25 hours) on Days 1, 2 and 3

Title

Cmax: Maximum Observed Plasma Concentration for TAK-954

Time Frame

Predose and at multiple time-points post-dose (up to 25 hours) on Days 1, 2 and 3

Title

Ctrough: Observed Plasma Concentration at the End of a Dosing Interval

Time Frame

At multiple time-points post-dose, up to 9 hours on Day 2 and up to 25 hours on Day 3

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Has diabetes mellitus with symptoms of gastroparesis and previously documented gastric emptying delay or previously documented idiopathic gastroparesis in the last 5 years. Has a body mass index (BMI) greater than or equal to (>=) 16 and less than or equal to (<=) 40 kilogram per square meter (kg/m^2) at the Screening Visit. Exclusion Criteria: Has glycosylated hemoglobin (HbA1c) greater than (>) 12 percent (%). Has other structural diseases/conditions that affect the gastrointestinal (GI) system. Are unable to withdraw drugs known to alter GI transit 48 hours prior to the study. Has clinically significant abnormal baseline safety laboratory values. Has preexisting hepatic disease that meets Child-Pugh Class B (moderate; total score 7 to 9 points) or C (severe; total score 10 to 15 points). Are without known preexisting hepatic disease who have 1 or more of the following: Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2 times the upper limit of normal (ULN). Bilirubin >1.5 times the ULN unless due to Gilbert's syndrome. International normalized ratio (INR) >1.5 unless on anticoagulation therapy. Has QT intervals with Fridericia correction method (QTcF) interval (>=) 460 millisecond (msec) or with other factors that increase the risk of QT prolongation or arrhythmic events at screening. Note: Participants with bundle branch block and a prolonged QTc interval, or with QTcF between 450 and 460 msec, should be reviewed by the Medical Monitor for potential inclusion. Has second or third degree atrioventricular (AV) block; AV disassociation; >5 beats of non-sustained VT at a rate >120 beats per minute (bpm); Electrocardiogram (ECG) changes consistent with acute myocardial ischemia or infarction. Has cardiac history that includes conditions requiring heart rate control (example, atrial fibrillation, atrial flutter, ventricular tachycardia, or other tachyarrhythmias). Has clinical evidence (including physical examination, ECG, clinical laboratory value and review of the medical history) of significant cardiovascular, respiratory, moderate or severe renal insufficiency (creatinine clearance <=60 mL/min), hematological, neurological, or psychiatric disease, or other disease that interferes with the objectives of the study. If female, are pregnant or lactating or intending to become pregnant before participating in this study, during the study, and 4 to 5 days (5 half-lives) PLUS 30 days after last dose of the study drug; or intending to donate ova during such time period. Are considered by the investigator to be alcoholics not in remission or known substance abusers. Have a history of alcohol consumption exceeding 2 standard drinks per day on average (1 glass is approximately equivalent to: beer [354 milliliter per [mL/] 12 ounces], wine [118 mL/4 ounces], or distilled spirits [29.5 mL/1 ounce] per day).

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Medical Director Clinical Science

Organizational Affiliation

Takeda

Official's Role

Study Director

Facility Information:

Facility Name

Mayo Clinic

City

Rochester

State/Province

Minnesota

ZIP/Postal Code

55905

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.

IPD Sharing Access Criteria

IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.

IPD Sharing URL

https://vivli.org/ourmember/takeda/

Citations:

PubMed Identifier

33711180

Citation

Chedid V, Brandler J, Arndt K, Vijayvargiya P, Wang XJ, Burton D, Harmsen WS, Siegelman J, Chen C, Chen Y, Almansa C, Dukes G, Camilleri M. Randomised study: effects of the 5-HT4 receptor agonist felcisetrag vs placebo on gut transit in patients with gastroparesis. Aliment Pharmacol Ther. 2021 May;53(9):1010-1020. doi: 10.1111/apt.16304. Epub 2021 Mar 12.

Results Reference

derived

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Effect of TAK-954 on Gastrointestinal and Colonic Transit in Diabetic or Idiopathic Gastroparesis Participants

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