Effect of TAK-954 on Gastrointestinal and Colonic Transit in Diabetic or Idiopathic Gastroparesis Participants
Sponsor
Takeda (Industry)
Overall Status
Completed
CT.gov ID
NCT03281577
Collaborator
(none)
36
1
4
18.3
2
Study Details
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 |
|---|---|---|
|
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
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
:
Jan 2, 2018
Actual Primary Completion Date
:
Jun 7, 2019
Actual Study Completion Date
:
Jul 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
- 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.
Secondary Outcome Measures
- Colonic Geometric Center [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.
- Colonic Filling at Hour 6 [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.
- Half-emptying Time (T1/2) of Ascending Colon [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.
- AUCtau: Area Under the Plasma Concentration-Time Curve From Time 0 to t for TAK-954 [Predose and at multiple time-points post-dose (up to 25 hours) on Days 1, 2 and 3]
- Cmax: Maximum Observed Plasma Concentration for TAK-954 [Predose and at multiple time-points post-dose (up to 25 hours) on Days 1, 2 and 3]
- Ctrough: Observed Plasma Concentration at the End of a Dosing Interval [At multiple time-points post-dose, up to 9 hours on Day 2 and up to 25 hours on Day 3]
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 65 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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).
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Mayo Clinic | Rochester | Minnesota | United States | 55905 |
Sponsors and Collaborators
- Takeda
Investigators
- Study Director: Medical Director Clinical Science, Takeda
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Takeda
ClinicalTrials.gov Identifier:
NCT03281577
Other Study ID Numbers:
- TAK-954-2003
- U1111-1200-9396
First Posted:
Sep 13, 2017
Last Update Posted:
Jan 7, 2021
Last Verified:
Dec 1, 2020
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Takeda
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Participants took part in the study at 1 investigative site in the United States from 02 January 2018 to 12 July 2019. |
|---|---|
| Pre-assignment Detail | Participants with a diagnosis of diabetic or idiopathic gastroparesis were enrolled and randomized in 1:1:1:1 ratio to receive TAK-954 0.1 mg, 0.3 mg, 1 mg or placebo. |
| Arm/Group Title | Placebo | TAK-954 0.1 mg | TAK-954 0.3 mg | TAK-954 1 mg |
|---|---|---|---|---|
| Arm/Group 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 0.3 mg, 60-minute infusion, IV, once daily on Days 1 to 3. | TAK-954 1 mg, 60-minute infusion, IV, once daily on Days 1 to 3. |
| Period Title: Overall Study | ||||
| STARTED | 10 | 10 | 9 | 7 |
| COMPLETED | 9 | 10 | 9 | 6 |
| NOT COMPLETED | 1 | 0 | 0 | 1 |
Baseline Characteristics
| Arm/Group Title | Placebo | TAK-954 0.1 mg | TAK-954 0.3 mg | TAK-954 1 mg | Total |
|---|---|---|---|---|---|
| Arm/Group Description | TAK-954 placebo-matching, 60-minute infusion, 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 0.3 mg, 60-minute infusion, IV, once daily on Days 1 to 3. | TAK-954 1 mg, 60-minute infusion, IV, once daily on Days 1 to 3. | Total of all reporting groups |
| Overall Participants | 10 | 10 | 9 | 7 | 36 |
| Age (years) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [years] |
46.2
(15.67)
|
46.8
(12.45)
|
42.3
(11.82)
|
40.3
(8.75)
|
44.3
(12.45)
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
8
80%
|
10
100%
|
7
77.8%
|
5
71.4%
|
30
83.3%
|
| Male |
2
20%
|
0
0%
|
2
22.2%
|
2
28.6%
|
6
16.7%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||||
| Hispanic or Latino |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Not Hispanic or Latino |
9
90%
|
9
90%
|
9
100%
|
7
100%
|
34
94.4%
|
| Unknown or Not Reported |
1
10%
|
1
10%
|
0
0%
|
0
0%
|
2
5.6%
|
| Race/Ethnicity, Customized (Count of Participants) | |||||
| White |
10
100%
|
10
100%
|
9
100%
|
7
100%
|
36
100%
|
| Disease History (Count of Participants) | |||||
| Idiopathic Gastroparesis |
7
70%
|
7
70%
|
3
33.3%
|
5
71.4%
|
22
61.1%
|
| Diabetic Gastroparesis |
3
30%
|
3
30%
|
6
66.7%
|
2
28.6%
|
14
38.9%
|
| Weight (kg) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [kg] |
68.3
(15.05)
|
73.4
(14.57)
|
76.5
(17.97)
|
62.5
(9.22)
|
70.6
(15.07)
|
| Height (cm) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [cm] |
166.2
(9.37)
|
160.7
(7.27)
|
165.7
(5.92)
|
166.3
(7.57)
|
164.6
(7.74)
|
| Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [kg/m^2] |
24.8
(4.88)
|
28.4
(5.50)
|
27.7
(5.44)
|
22.6
(3.15)
|
26.1
(5.24)
|
Outcome Measures
| Title | Percent Change From Baseline in Half-emptying Time (T1/2) of Gastric Solids |
|---|---|
| Description | 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. |
| Time Frame | Predose and at multiple time-points post-dose (up to 9 hours) on Day 2 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set included all randomized participants who received at least 1 dose of study drug. Overall number of participants analyzed is number of participants with data available for analyses. |
| Arm/Group Title | Placebo | TAK-954 0.1 mg | TAK-954 0.3 mg | TAK-954 1 mg |
|---|---|---|---|---|
| Arm/Group Description | TAK-954 placebo-matching, 60-minute infusion, 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 0.3 mg, 60-minute infusion, IV, once daily on Days 1 to 3. | TAK-954 1 mg, 60-minute infusion, IV, once daily on Days 1 to 3. |
| Measure Participants | 9 | 10 | 9 | 6 |
| Mean (Standard Deviation) [percent change] |
3.5
(23.71)
|
-19.8
(14.43)
|
-25.4
(20.90)
|
-25.7
(23.56)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, TAK-954 0.1 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0012 |
| Comments | Dunnett's test was used to compare each treatment arm to placebo. Multiplicity Adjusted p-value and 95% confidence interval (CI) are presented. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Differences |
| Estimated Value | -25.81 | |
| Confidence Interval |
(2-Sided) 95% -41.757 to -9.858 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Linear mixed effects model used for analyses using gastroparesis type [diabetic or idiopathic], age, gender, BMI, baseline as covariate. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, TAK-954 0.3 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0018 |
| Comments | Dunnett's test was used to compare each treatment arm to placebo. Multiplicity Adjusted p-value and 95% CI are presented. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Differences |
| Estimated Value | -27.52 | |
| Confidence Interval |
(2-Sided) 95% -45.224 to -9.813 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Linear mixed effects model used for analyses using gastroparesis type [diabetic or idiopathic], age, gender, BMI, baseline as a covariate. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo, TAK-954 1 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <.0001 |
| Comments | Dunnett's test was used to compare each treatment arm to placebo. Multiplicity Adjusted p-value and 95% CI are presented. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Differences |
| Estimated Value | -41.76 | |
| Confidence Interval |
(2-Sided) 95% -59.616 to -23.902 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Linear mixed effects model used for analyses using gastroparesis type [diabetic or idiopathic], age, gender, BMI, baseline as a covariate. | |
| Title | Colonic Geometric Center |
|---|---|
| Description | 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. |
| Time Frame | 4, 24, and 48 hours post-radiolabeled meal on Day 2 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set included all randomized participants who received at least 1 dose of study drug. Number analyzed is the number of participants with evaluable data at the given time point. |
| Arm/Group Title | Placebo | TAK-954 0.1 mg | TAK-954 0.3 mg | TAK-954 1 mg |
|---|---|---|---|---|
| Arm/Group Description | TAK-954 placebo-matching, 60-minute infusion, 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 0.3 mg, 60-minute infusion, IV, once daily on Days 1 to 3. | TAK-954 1 mg, 60-minute infusion, IV, once daily on Days 1 to 3. |
| Measure Participants | 10 | 10 | 9 | 7 |
| Colonic Transit at 4 Hours, Day 2 |
0.539
(0.6809)
|
1.190
(0.9083)
|
1.737
(1.0302)
|
1.148
(0.4138)
|
| Colonic Transit at 24 Hours, Day 2 |
1.965
(1.2964)
|
3.792
(1.1441)
|
3.468
(1.3252)
|
2.978
(1.1382)
|
| Colonic Transit at 48 Hours, Day 2 |
3.323
(1.2948)
|
4.406
(1.1169)
|
4.550
(0.9004)
|
3.792
(1.0382)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, TAK-954 0.1 mg |
|---|---|---|
| Comments | Colonic Transit at 4 Hours, Day 2 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2590 |
| Comments | Dunnett's test was used to compare each treatment arm to placebo. Multiplicity Adjusted p-value and 95% CI are presented. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Differences |
| Estimated Value | 0.72 | |
| Confidence Interval |
(2-Sided) 95% -0.364 to 1.795 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Linear mixed effects model used for analyses using gastroparesis type [diabetic or idiopathic], age, gender, BMI, baseline as a covariate. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, TAK-954 0.3 mg |
|---|---|---|
| Comments | Colonic Transit at 4 Hours, Day 2 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0280 |
| Comments | Dunnett's test was used to compare each treatment arm to placebo. Multiplicity Adjusted p-value and 95% CI are presented. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Differences |
| Estimated Value | 1.27 | |
| Confidence Interval |
(2-Sided) 95% 0.119 to 2.418 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Linear mixed effects model used for analyses using gastroparesis type [diabetic or idiopathic], age, gender, BMI, baseline as a covariate. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo, TAK-954 1 mg |
|---|---|---|
| Comments | Colonic Transit at 4 Hours, Day 2 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6882 |
| Comments | Dunnett's test was used to compare each treatment arm to placebo. Multiplicity Adjusted p-value and 95% CI are presented. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Differences |
| Estimated Value | 0.45 | |
| Confidence Interval |
(2-Sided) 95% -0.757 to 1.660 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Linear mixed effects model used for analyses using gastroparesis type [diabetic or idiopathic], age, gender, BMI, baseline as a covariate. | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Placebo, TAK-954 0.1 mg |
|---|---|---|
| Comments | Colonic Transit at 24 Hours, Day 2 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0062 |
| Comments | Dunnett's test was used to compare each treatment arm to placebo. Multiplicity Adjusted p-value and 95% CI are presented. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Differences |
| Estimated Value | 1.87 | |
| Confidence Interval |
(2-Sided) 95% 0.493 to 3.250 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Linear mixed effects model used for analyses using gastroparesis type [diabetic or idiopathic], age, gender, BMI, baseline as a covariate. | |
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Placebo, TAK-954 0.3 mg |
|---|---|---|
| Comments | Colonic Transit at 24 Hours, Day 2 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1490 |
| Comments | Dunnett's test was used to compare each treatment arm to placebo. Multiplicity Adjusted p-value and 95% CI are presented. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Differences |
| Estimated Value | 1.19 | |
| Confidence Interval |
(2-Sided) 95% -0.327 to 2.717 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Linear mixed effects model used for analyses using gastroparesis type [diabetic or idiopathic], age, gender, BMI, baseline as a covariate. | |
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Placebo, TAK-954 1 mg |
|---|---|---|
| Comments | Colonic Transit at 24 Hours, Day 2 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6285 |
| Comments | Dunnett's test was used to compare each treatment arm to placebo. Multiplicity Adjusted p-value and 95% CI are presented. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Differences |
| Estimated Value | 0.63 | |
| Confidence Interval |
(2-Sided) 95% -0.931 to 2.200 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Linear mixed effects model used for analyses using gastroparesis type [diabetic or idiopathic], age, gender, BMI, baseline as a covariate. | |
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Placebo, TAK-954 0.1 mg |
|---|---|---|
| Comments | Colonic Transit at 48 Hours, Day 2 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0358 |
| Comments | Dunnett's test was used to compare each treatment arm to placebo. Multiplicity Adjusted p-value and 95% CI are presented. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Differences |
| Estimated Value | 1.29 | |
| Confidence Interval |
(2-Sided) 95% 0.073 to 2.501 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Linear mixed effects model used for analyses using gastroparesis type [diabetic or idiopathic], age, gender, BMI, baseline as a covariate. | |
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Placebo, TAK-954 0.3 mg |
|---|---|---|
| Comments | Colonic Transit at 48 Hours, Day 2 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0430 |
| Comments | Dunnett's test was used to compare each treatment arm to placebo. Multiplicity Adjusted p-value and 95% CI are presented. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Differences |
| Estimated Value | 1.33 | |
| Confidence Interval |
(2-Sided) 95% 0.035 to 2.621 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Linear mixed effects model used for analyses using gastroparesis type [diabetic or idiopathic], age, gender, BMI, baseline as a covariate. | |
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Placebo, TAK-954 1 mg |
|---|---|---|
| Comments | Colonic Transit at 48 Hours, Day 2 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9419 |
| Comments | Dunnett's test was used to compare each treatment arm to placebo. Multiplicity Adjusted p-value and 95% CI are presented. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Differences |
| Estimated Value | 0.25 | |
| Confidence Interval |
(2-Sided) 95% -1.107 to 1.611 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Linear mixed effects model used for analyses using gastroparesis type [diabetic or idiopathic], age, gender, BMI, baseline as a covariate. | |
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set included all randomized participants who received at least 1 dose of study drug. Overall number of participants analyzed is number of participants with data available for analyses. |
| Arm/Group Title | Placebo | TAK-954 0.1 mg | TAK-954 0.3 mg | TAK-954 1 mg |
|---|---|---|---|---|
| Arm/Group Description | TAK-954 placebo-matching, 60-minute infusion, 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 0.3 mg, 60-minute infusion, IV, once daily on Days 1 to 3. | TAK-954 1 mg, 60-minute infusion, IV, once daily on Days 1 to 3. |
| Measure Participants | 9 | 10 | 9 | 6 |
| Mean (Standard Deviation) [percentage of radio-labelled food] |
31.3
(25.38)
|
55.6
(31.31)
|
86.4
(19.76)
|
75.3
(31.70)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, TAK-954 0.1 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0436 |
| Comments | Dunnett's test was used to compare each treatment arm to placebo. Multiplicity Adjusted p-value and 95% CI are presented. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Differences |
| Estimated Value | 33.12 | |
| Confidence Interval |
(2-Sided) 95% 0.799 to 65.439 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Linear mixed effects model used for analyses using gastroparesis type [diabetic or idiopathic], age, gender, BMI, baseline as a covariate. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, TAK-954 0.3 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0007 |
| Comments | Dunnett's test was used to compare each treatment arm to placebo. Multiplicity Adjusted p-value and 95% CI are presented. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Differences |
| Estimated Value | 57.98 | |
| Confidence Interval |
(2-Sided) 95% 23.555 to 92.396 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Linear mixed effects model used for analyses using gastroparesis type [diabetic or idiopathic], age, gender, BMI, baseline as a covariate. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo, TAK-954 1 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0134 |
| Comments | Dunnett's test was used to compare each treatment arm to placebo. Multiplicity Adjusted p-value and 95% CI are presented. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Differences |
| Estimated Value | 44.44 | |
| Confidence Interval |
(2-Sided) 95% 8.249 to 80.629 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Linear mixed effects model used for analyses using gastroparesis type [diabetic or idiopathic], age, gender, BMI, baseline as a covariate. | |
| Title | Half-emptying Time (T1/2) of Ascending Colon |
|---|---|
| Description | 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. |
| Time Frame | Predose and at multiple time-points post-dose (up to 25 hours) on Days 1, 2 and 3 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set included all randomized participants who received at least 1 dose of study drug. Overall number of participants analyzed is the number of participants with data available for analyses. |
| Arm/Group Title | Placebo | TAK-954 0.1 mg | TAK-954 0.3 mg | TAK-954 1 mg |
|---|---|---|---|---|
| Arm/Group Description | TAK-954 placebo-matching, 60-minute infusion, 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 0.3 mg, 60-minute infusion, IV, once daily on Days 1 to 3. | TAK-954 1 mg, 60-minute infusion, IV, once daily on Days 1 to 3. |
| Measure Participants | 9 | 10 | 9 | 6 |
| Median (Full Range) [hours] |
19.1
|
5.4
|
6.3
|
7.4
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, TAK-954 0.1 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0789 |
| Comments | Dunnett's test was used to compare each treatment arm to placebo. Multiplicity Adjusted p-value and 95% CI are presented. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Differences |
| Estimated Value | -10.27 | |
| Confidence Interval |
(2-Sided) 95% -21.507 to 0.960 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Linear mixed effects model used for analyses using gastroparesis type [diabetic or idiopathic], age, gender, BMI, baseline as a covariate. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, TAK-954 0.3 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0270 |
| Comments | Dunnett's test was used to compare each treatment arm to placebo. Multiplicity Adjusted p-value and 95% CI are presented. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Differences |
| Estimated Value | -13.28 | |
| Confidence Interval |
(2-Sided) 95% -25.242 to -1.314 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Linear mixed effects model used for analyses using gastroparesis type [diabetic or idiopathic], age, gender, BMI, baseline as a covariate. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo, TAK-954 1 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0750 |
| Comments | Dunnett's test was used to compare each treatment arm to placebo. Multiplicity Adjusted p-value and 95% CI are presented. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Differences |
| Estimated Value | -11.63 | |
| Confidence Interval |
(2-Sided) 95% -24.206 to 0.952 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Linear mixed effects model used for analyses using gastroparesis type [diabetic or idiopathic], age, gender, BMI, baseline as a covariate. | |
| Title | AUCtau: Area Under the Plasma Concentration-Time Curve From Time 0 to t for TAK-954 |
|---|---|
| Description | |
| Time Frame | Predose and at multiple time-points post-dose (up to 25 hours) on Days 1, 2 and 3 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic (PK) analysis set included all participants who received at least 1 dose of study drug and had sufficient blood sampling to allow for PK evaluation. Number analyzed is the number of participants with evaluable data at the given time point. |
| Arm/Group Title | TAK-954 0.1 mg | TAK-954 0.3 mg | TAK-954 1 mg |
|---|---|---|---|
| Arm/Group Description | TAK-954 0.1 mg, 60-minute infusion, IV, once daily on Days 1 to 3. | TAK-954 0.3 mg, 60-minute infusion, IV, once daily on Days 1 to 3. | TAK-954 1 mg, 60-minute infusion, IV, once daily on Days 1 to 3. |
| Measure Participants | 10 | 9 | 7 |
| Day 1 |
8.99
(2.110)
|
25.79
(8.340)
|
83.75
(25.453)
|
| Day 2 |
12.16
(3.033)
|
33.94
(9.249)
|
109.86
(31.009)
|
| Day 3 |
15.72
(3.387)
|
39.34
(12.699)
|
125.88
(34.586)
|
| Title | Cmax: Maximum Observed Plasma Concentration for TAK-954 |
|---|---|
| Description | |
| Time Frame | Predose and at multiple time-points post-dose (up to 25 hours) on Days 1, 2 and 3 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK analysis set included all participants who received at least 1 dose of study drug and had sufficient blood sampling to allow for PK evaluation. Number analyzed is the number of participants with evaluable data at the given time point. |
| Arm/Group Title | TAK-954 0.1 mg | TAK-954 0.3 mg | TAK-954 1 mg |
|---|---|---|---|
| Arm/Group Description | TAK-954 0.1 mg, 60-minute infusion, IV, once daily on Days 1 to 3. | TAK-954 0.3 mg, 60-minute infusion, IV, once daily on Days 1 to 3. | TAK-954 1 mg, 60-minute infusion, IV, once daily on Days 1 to 3. |
| Measure Participants | 10 | 9 | 7 |
| Day 1 |
1.637
(0.3918)
|
5.346
(1.5797)
|
16.029
(2.9239)
|
| Day 2 |
1.687
(0.4227)
|
5.821
(1.9447)
|
15.517
(3.7070)
|
| Day 3 |
1.705
(0.3297)
|
5.056
(1.5430)
|
17.700
(7.1544)
|
| Title | Ctrough: Observed Plasma Concentration at the End of a Dosing Interval |
|---|---|
| Description | |
| Time Frame | At multiple time-points post-dose, up to 9 hours on Day 2 and up to 25 hours on Day 3 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK analysis set included all participants who received at least 1 dose of study drug and had sufficient blood sampling to allow for PK evaluation. Number analyzed is the number of participants with evaluable data at the given time point. |
| Arm/Group Title | TAK-954 0.1 mg | TAK-954 0.3 mg | TAK-954 1 mg |
|---|---|---|---|
| Arm/Group Description | TAK-954 0.1 mg, 60-minute infusion, IV, once daily on Days 1 to 3. | TAK-954 0.3 mg, 60-minute infusion, IV, once daily on Days 1 to 3. | TAK-954 1 mg, 60-minute infusion, IV, once daily on Days 1 to 3. |
| Measure Participants | 10 | 9 | 7 |
| Day 2 |
0.1969
(0.05406)
|
0.4364
(0.20371)
|
1.6817
(0.47072)
|
| Day 3 |
0.2854
(0.10319)
|
0.6392
(0.26371)
|
2.2620
(0.40493)
|
Adverse Events
| Time Frame | From first dose up to 30 days post last dose (Up to 46 days) | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. | |||||||
| Arm/Group Title | Placebo | TAK-954 0.1 mg | TAK-954 0.3 mg | TAK-954 1 mg | ||||
| Arm/Group Description | TAK-954 placebo-matching, 60-minute infusion, 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 0.3 mg, 60-minute infusion, IV, once daily on Days 1 to 3. | TAK-954 1 mg, 60-minute infusion, IV, once daily on Days 1 to 3. | ||||
All Cause Mortality |
||||||||
| Placebo | TAK-954 0.1 mg | TAK-954 0.3 mg | TAK-954 1 mg | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/10 (0%) | 0/10 (0%) | 0/9 (0%) | 0/7 (0%) | ||||
Serious Adverse Events |
||||||||
| Placebo | TAK-954 0.1 mg | TAK-954 0.3 mg | TAK-954 1 mg | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/10 (0%) | 0/10 (0%) | 0/9 (0%) | 1/7 (14.3%) | ||||
| Investigations | ||||||||
| Pancreatic enzymes increased | 0/10 (0%) | 0/10 (0%) | 0/9 (0%) | 1/7 (14.3%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| Placebo | TAK-954 0.1 mg | TAK-954 0.3 mg | TAK-954 1 mg | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 6/10 (60%) | 5/10 (50%) | 6/9 (66.7%) | 6/7 (85.7%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Leukocytosis | 0/10 (0%) | 0/10 (0%) | 0/9 (0%) | 1/7 (14.3%) | ||||
| Eye disorders | ||||||||
| Eye swelling | 0/10 (0%) | 0/10 (0%) | 0/9 (0%) | 1/7 (14.3%) | ||||
| Gastrointestinal disorders | ||||||||
| Nausea | 4/10 (40%) | 4/10 (40%) | 2/9 (22.2%) | 4/7 (57.1%) | ||||
| Diarrhoea | 0/10 (0%) | 2/10 (20%) | 1/9 (11.1%) | 4/7 (57.1%) | ||||
| Abdominal pain | 0/10 (0%) | 3/10 (30%) | 0/9 (0%) | 2/7 (28.6%) | ||||
| Abdominal distension | 2/10 (20%) | 0/10 (0%) | 1/9 (11.1%) | 2/7 (28.6%) | ||||
| Gastrooesophageal reflux disease | 1/10 (10%) | 0/10 (0%) | 0/9 (0%) | 2/7 (28.6%) | ||||
| Flatulence | 0/10 (0%) | 1/10 (10%) | 0/9 (0%) | 1/7 (14.3%) | ||||
| Vomiting | 0/10 (0%) | 1/10 (10%) | 0/9 (0%) | 0/7 (0%) | ||||
| Abdominal pain lower | 0/10 (0%) | 0/10 (0%) | 0/9 (0%) | 1/7 (14.3%) | ||||
| General disorders | ||||||||
| Fatigue | 1/10 (10%) | 0/10 (0%) | 0/9 (0%) | 1/7 (14.3%) | ||||
| Chills | 0/10 (0%) | 1/10 (10%) | 0/9 (0%) | 1/7 (14.3%) | ||||
| Sensation of foreign body | 0/10 (0%) | 0/10 (0%) | 0/9 (0%) | 1/7 (14.3%) | ||||
| Oedema peripheral | 0/10 (0%) | 0/10 (0%) | 0/9 (0%) | 1/7 (14.3%) | ||||
| Infusion site pain | 0/10 (0%) | 0/10 (0%) | 1/9 (11.1%) | 0/7 (0%) | ||||
| Drug withdrawal syndrome | 0/10 (0%) | 0/10 (0%) | 0/9 (0%) | 1/7 (14.3%) | ||||
| Asthenia | 0/10 (0%) | 0/10 (0%) | 0/9 (0%) | 1/7 (14.3%) | ||||
| Infections and infestations | ||||||||
| Viral infection | 0/10 (0%) | 2/10 (20%) | 0/9 (0%) | 0/7 (0%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Dehydration | 0/10 (0%) | 0/10 (0%) | 0/9 (0%) | 2/7 (28.6%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Pain in extremity | 0/10 (0%) | 0/10 (0%) | 1/9 (11.1%) | 0/7 (0%) | ||||
| Musculoskeletal pain | 0/10 (0%) | 0/10 (0%) | 1/9 (11.1%) | 0/7 (0%) | ||||
| Back pain | 1/10 (10%) | 0/10 (0%) | 0/9 (0%) | 0/7 (0%) | ||||
| Arthralgia | 0/10 (0%) | 0/10 (0%) | 1/9 (11.1%) | 0/7 (0%) | ||||
| Nervous system disorders | ||||||||
| Headache | 0/10 (0%) | 1/10 (10%) | 3/9 (33.3%) | 1/7 (14.3%) | ||||
| Dizziness | 0/10 (0%) | 0/10 (0%) | 1/9 (11.1%) | 2/7 (28.6%) | ||||
| Presyncope | 0/10 (0%) | 0/10 (0%) | 1/9 (11.1%) | 0/7 (0%) | ||||
| Dysgeusia | 0/10 (0%) | 0/10 (0%) | 0/9 (0%) | 1/7 (14.3%) | ||||
| Psychiatric disorders | ||||||||
| Insomnia | 0/10 (0%) | 0/10 (0%) | 1/9 (11.1%) | 0/7 (0%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Epistaxis | 1/10 (10%) | 0/10 (0%) | 0/9 (0%) | 0/7 (0%) | ||||
| Cough | 0/10 (0%) | 0/10 (0%) | 0/9 (0%) | 1/7 (14.3%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Pruritus | 0/10 (0%) | 0/10 (0%) | 1/9 (11.1%) | 1/7 (14.3%) | ||||
| Urticaria | 0/10 (0%) | 0/10 (0%) | 0/9 (0%) | 1/7 (14.3%) | ||||
| Cold sweat | 1/10 (10%) | 0/10 (0%) | 0/9 (0%) | 0/7 (0%) | ||||
| Vascular disorders | ||||||||
| Orthostatic hypotension | 0/10 (0%) | 0/10 (0%) | 1/9 (11.1%) | 0/7 (0%) | ||||
| Flushing | 0/10 (0%) | 0/10 (0%) | 0/9 (0%) | 1/7 (14.3%) | ||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi-site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
Results Point of Contact
| Name/Title | Medical Director |
|---|---|
| Organization | Takeda |
| Phone | +1-877-825-3327 |
| takedadisclosures@takeda.com |
Responsible Party:
Takeda
ClinicalTrials.gov Identifier:
NCT03281577
Other Study ID Numbers:
- TAK-954-2003
- U1111-1200-9396
First Posted:
Sep 13, 2017
Last Update Posted:
Jan 7, 2021
Last Verified:
Dec 1, 2020