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

• ClinicalTrials.gov Identifier: NCT03281577
• Recruitment Status: Completed
• First Posted: September 13, 2017
• Results First Posted: July 15, 2020
• Last Update Posted: January 7, 2021
• Sponsor: Takeda
• Information provided by (Responsible Party): Takeda

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.

Condition or disease	Intervention/treatment	Phase
Diabetic Gastroparesis; Idiopathic Gastroparesis	Drug: TAK-954; Drug: Placebo	Phase 2

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).

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 36 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: January 2, 2018
• Actual Primary Completion Date: June 7, 2019
• Actual Study Completion Date: July 12, 2019

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Placebo; TAK-954 placebo-matching, 60-minute infusion, intravenously (IV), once daily on Days 1 to 3.	Drug: Placebo; TAK-954 placebo-matching IV infusion.
Experimental: TAK-954 0.1 mg; TAK-954 0.1 mg, 60-minute infusion, IV, once daily on Days 1 to 3.	Drug: TAK-954; TAK-954 IV infusion.
Experimental: TAK-954 0.3 mg; TAK-954 1 mg, 60-minute infusion, IV, once daily for up to 3 days.	Drug: TAK-954; TAK-954 IV infusion.
Experimental: TAK-954 1 mg; TAK-954 1 mg, 60-minute infusion, IV, once daily on Days 1 to 3.	Drug: TAK-954; TAK-954 IV infusion.

Outcome Measures

Primary Outcome Measures :

1. Percent Change From Baseline in Half-emptying Time (T1/2) of Gastric Solids [ Time Frame: 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.

Secondary Outcome Measures :

1. Colonic Geometric Center [ Time Frame: 4, 24, and 48 hours post-radiolabeled meal on Day 2 ]
   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.
2. Colonic Filling at Hour 6 [ Time Frame: 6 hours post-radiolabel meal on Day 2 ]
   Colonic filling was estimated as percentage of the radio-labelled meal that reached the colon at Hour 6.
3. Half-emptying Time (T1/2) of Ascending Colon [ Time Frame: Predose and at multiple time-points post-dose (up to 25 hours) on Days 1, 2 and 3 ]
   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.
4. 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 ]
5. 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 ]
6. 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 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Has diabetes mellitus with symptoms of gastroparesis and previously documented gastric emptying delay or previously documented idiopathic gastroparesis in the last 5 years.
2. 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:

1. Has glycosylated hemoglobin (HbA1c) greater than (>) 12 percent (%).
2. Has other structural diseases/conditions that affect the gastrointestinal (GI) system.
3. Are unable to withdraw drugs known to alter GI transit 48 hours prior to the study.
4. Has clinically significant abnormal baseline safety laboratory values.
5. 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).

6. 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.
7. 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.
8. 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.
9. Has cardiac history that includes conditions requiring heart rate control (example, atrial fibrillation, atrial flutter, ventricular tachycardia, or other tachyarrhythmias).
10. 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.
11. 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.
12. 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).

Contacts and Locations

Locations

United States, Minnesota

Mayo Clinic

Rochester, Minnesota, United States, 55905

Sponsors and Collaborators

Takeda

Investigators

• Study Director: Medical Director Clinical Science; Takeda

  Study Documents (Full-Text)

Documents provided by Takeda:

Study Protocol  [PDF] December 19, 2018

Statistical Analysis Plan  [PDF] September 25, 2018

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT03281577
• Other Study ID Numbers: TAK-954-2003; U1111-1200-9396 ( Registry Identifier: WHO )
• First Posted: September 13, 2017
• Results First Posted: July 15, 2020
• Last Update Posted: January 7, 2021
• Last Verified: December 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)
• 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.
• URL: https://vivli.org/ourmember/takeda/

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Takeda:

Drug Therapy

Additional relevant MeSH terms:

Gastroparesis; Stomach Diseases; Gastrointestinal Diseases; Digestive System Diseases; Paralysis; Neurologic Manifestations