Trial Outcomes & Findings for A Study to Evaluate the Efficacy and Safety of TAK-906 in Adult Participants With Symptomatic Idiopathic or Diabetic Gastroparesis (NCT NCT03544229)

Last Updated: 2022-11-16

Results Overview

ANMS GCSI-DD is a patient-reported outcome instrument for a symptom-based clinical trial endpoint in gastroparesis. The ANMS GCSI-DD composite score included score of nausea, early satiety, upper abdominal pain, and postprandial fullness. The severity scores of these symptoms range from 0 (none) to 4 (very severe). The daily composite score was calculated by summing the scores on the 4 symptom items (nausea, early satiety, postprandial fullness, and upper abdominal pain) and then dividing by 4, that is the number of items within the composite score. Thus, the maximum daily composite score was (4 symptoms × maximum score 4 divided by 4) = 16/4 = 4. The ANMS GCSI-DD daily composite score ranged from 0 to 4 with higher scores reflecting greater symptom severity. The negative change from baseline indicates improvement. Mixed-effects Model for Repeated Measures (MMRM) was used for the analysis.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

242 participants

Primary outcome timeframe

Baseline and Week 12

Results posted on

2022-11-16

Participant Flow

Participants with symptomatic idiopathic or diabetic gastroparesis took part in the study at 73 investigative sites in Belgium, Poland, Japan and the United States from 14 October 2018 to 15 July 2021.

Participants receive TAK-906 5 mg, 25 mg, 50 mg Maleate or placebo in 1:1:1:1 ratio until protocol amendment 8 was implemented. As pre-specified in protocol amendment 8 further randomization TAK-906 5 mg arm was discontinued and remaining enrolled participants were randomized into TAK-906 25 mg, TAK-906 50 mg Maleate or placebo in 1:1:1 ratio.

Participant milestones

Participant milestones
Measure	Placebo TAK-906 maleate placebo-matching capsules, orally, twice daily (BID) for up to 12 weeks.	TAK-906 Maleate 5 mg TAK-906 maleate 5 mg, capsules, orally, BID for up to 12 weeks.	TAK-906 Maleate 25 mg TAK-906 maleate 25 mg, capsules, orally, BID for up to 12 weeks.	TAK-906 Maleate 50 mg TAK-906 maleate 50 mg, capsules, orally, BID for up to 12 weeks.
Overall Study STARTED	73	23	72	74
Overall Study COMPLETED	67	21	67	72
Overall Study NOT COMPLETED	6	2	5	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo TAK-906 maleate placebo-matching capsules, orally, twice daily (BID) for up to 12 weeks.	TAK-906 Maleate 5 mg TAK-906 maleate 5 mg, capsules, orally, BID for up to 12 weeks.	TAK-906 Maleate 25 mg TAK-906 maleate 25 mg, capsules, orally, BID for up to 12 weeks.	TAK-906 Maleate 50 mg TAK-906 maleate 50 mg, capsules, orally, BID for up to 12 weeks.
Overall Study Adverse Event	1	0	1	0
Overall Study Protocol Deviation	0	0	1	0
Overall Study Lost to Follow-up	3	0	0	2
Overall Study Voluntary Withdrawal	2	1	3	0
Overall Study Lack of Efficacy	0	1	0	0

Baseline Characteristics

FAS included all participants who were randomized, received at least 1 dose of study drug, and have a baseline value and at least 1 valid postbaseline value for assessment of primary efficacy.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=73 Participants TAK-906 maleate placebo-matching capsules, orally, BID for up to 12 weeks.	TAK-906 Maleate 5 mg n=23 Participants TAK-906 maleate 5 mg, capsules, orally, BID for up to 12 weeks.	TAK-906 Maleate 25 mg n=72 Participants TAK-906 maleate 25 mg, capsules, orally, BID for up to 12 weeks.	TAK-906 Maleate 50 mg n=74 Participants TAK-906 maleate 50 mg, capsules, orally, BID for up to 12 weeks.	Total n=242 Participants Total of all reporting groups
Age, Continuous	57.1 years STANDARD_DEVIATION 14.22 • n=5 Participants	56.3 years STANDARD_DEVIATION 14.32 • n=7 Participants	56.4 years STANDARD_DEVIATION 13.31 • n=5 Participants	53.4 years STANDARD_DEVIATION 15.09 • n=4 Participants	55.7 years STANDARD_DEVIATION 14.24 • n=21 Participants
Sex: Female, Male Female	54 Participants n=5 Participants	19 Participants n=7 Participants	61 Participants n=5 Participants	49 Participants n=4 Participants	183 Participants n=21 Participants
Sex: Female, Male Male	19 Participants n=5 Participants	4 Participants n=7 Participants	11 Participants n=5 Participants	25 Participants n=4 Participants	59 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	30 Participants n=5 Participants	14 Participants n=7 Participants	38 Participants n=5 Participants	28 Participants n=4 Participants	110 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	42 Participants n=5 Participants	9 Participants n=7 Participants	34 Participants n=5 Participants	45 Participants n=4 Participants	130 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	2 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Asian	8 Participants n=5 Participants	4 Participants n=7 Participants	12 Participants n=5 Participants	15 Participants n=4 Participants	39 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	10 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants	11 Participants n=4 Participants	26 Participants n=21 Participants
Race (NIH/OMB) White	54 Participants n=5 Participants	18 Participants n=7 Participants	55 Participants n=5 Participants	45 Participants n=4 Participants	172 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants	4 Participants n=21 Participants
Region of Enrollment Belgium	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants	3 Participants n=4 Participants	9 Participants n=21 Participants
Region of Enrollment Japan	8 Participants n=5 Participants	4 Participants n=7 Participants	10 Participants n=5 Participants	13 Participants n=4 Participants	35 Participants n=21 Participants
Region of Enrollment Poland	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants	6 Participants n=21 Participants
Region of Enrollment United States of America	60 Participants n=5 Participants	19 Participants n=7 Participants	57 Participants n=5 Participants	56 Participants n=4 Participants	192 Participants n=21 Participants
Height	164.17 centimetres (cm) STANDARD_DEVIATION 10.238 • n=5 Participants	164.43 centimetres (cm) STANDARD_DEVIATION 9.178 • n=7 Participants	161.32 centimetres (cm) STANDARD_DEVIATION 7.313 • n=5 Participants	166.12 centimetres (cm) STANDARD_DEVIATION 8.841 • n=4 Participants	163.94 centimetres (cm) STANDARD_DEVIATION 9.054 • n=21 Participants
Weight	79.35 kilograms (kg) STANDARD_DEVIATION 16.383 • n=5 Participants	82.62 kilograms (kg) STANDARD_DEVIATION 17.021 • n=7 Participants	71.97 kilograms (kg) STANDARD_DEVIATION 16.261 • n=5 Participants	78.77 kilograms (kg) STANDARD_DEVIATION 15.201 • n=4 Participants	77.29 kilograms (kg) STANDARD_DEVIATION 16.36 • n=21 Participants
Body Mass Index (BMI)	29.35 kg/m^2 STANDARD_DEVIATION 5.003 • n=5 Participants	30.48 kg/m^2 STANDARD_DEVIATION 5.606 • n=7 Participants	27.61 kg/m^2 STANDARD_DEVIATION 5.835 • n=5 Participants	28.52 kg/m^2 STANDARD_DEVIATION 4.934 • n=4 Participants	28.69 kg/m^2 STANDARD_DEVIATION 5.343 • n=21 Participants
Smoking Classification Participant has Never Smoked	51 Participants n=5 Participants	18 Participants n=7 Participants	57 Participants n=5 Participants	54 Participants n=4 Participants	180 Participants n=21 Participants
Smoking Classification Participant is a Current Smoker	10 Participants n=5 Participants	1 Participants n=7 Participants	7 Participants n=5 Participants	5 Participants n=4 Participants	23 Participants n=21 Participants
Smoking Classification Participant is an Ex-smoker	12 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants	15 Participants n=4 Participants	39 Participants n=21 Participants
ANMS GCSI-DD Composite Score	2.59 score on a scale n=5 Participants • FAS included all participants who were randomized, received at least 1 dose of study drug, and have a baseline value and at least 1 valid postbaseline value for assessment of primary efficacy.	2.77 score on a scale n=7 Participants • FAS included all participants who were randomized, received at least 1 dose of study drug, and have a baseline value and at least 1 valid postbaseline value for assessment of primary efficacy.	2.57 score on a scale n=5 Participants • FAS included all participants who were randomized, received at least 1 dose of study drug, and have a baseline value and at least 1 valid postbaseline value for assessment of primary efficacy.	2.64 score on a scale n=4 Participants • FAS included all participants who were randomized, received at least 1 dose of study drug, and have a baseline value and at least 1 valid postbaseline value for assessment of primary efficacy.	2.62 score on a scale n=21 Participants • FAS included all participants who were randomized, received at least 1 dose of study drug, and have a baseline value and at least 1 valid postbaseline value for assessment of primary efficacy.
ANMS GCSI-DD Nausea Symptom Score	2.80 score on a scale n=5 Participants • FAS included all participants who were randomized, received at least 1 dose of study drug, and have a baseline value and at least 1 valid postbaseline value for assessment of primary efficacy.	2.85 score on a scale n=7 Participants • FAS included all participants who were randomized, received at least 1 dose of study drug, and have a baseline value and at least 1 valid postbaseline value for assessment of primary efficacy.	2.70 score on a scale n=5 Participants • FAS included all participants who were randomized, received at least 1 dose of study drug, and have a baseline value and at least 1 valid postbaseline value for assessment of primary efficacy.	2.72 score on a scale n=4 Participants • FAS included all participants who were randomized, received at least 1 dose of study drug, and have a baseline value and at least 1 valid postbaseline value for assessment of primary efficacy.	2.75 score on a scale n=21 Participants • FAS included all participants who were randomized, received at least 1 dose of study drug, and have a baseline value and at least 1 valid postbaseline value for assessment of primary efficacy.
ANMS GCSI-DD Early Satiety Symptom Score	2.80 score on a scale n=5 Participants • FAS included all participants who were randomized, received at least 1 dose of study drug, and have a baseline value and at least 1 valid postbaseline value for assessment of primary efficacy.	2.97 score on a scale n=7 Participants • FAS included all participants who were randomized, received at least 1 dose of study drug, and have a baseline value and at least 1 valid postbaseline value for assessment of primary efficacy.	2.82 score on a scale n=5 Participants • FAS included all participants who were randomized, received at least 1 dose of study drug, and have a baseline value and at least 1 valid postbaseline value for assessment of primary efficacy.	2.82 score on a scale n=4 Participants • FAS included all participants who were randomized, received at least 1 dose of study drug, and have a baseline value and at least 1 valid postbaseline value for assessment of primary efficacy.	2.83 score on a scale n=21 Participants • FAS included all participants who were randomized, received at least 1 dose of study drug, and have a baseline value and at least 1 valid postbaseline value for assessment of primary efficacy.
ANMS GCSI-DD Postprandial Fullness Symptom Score	2.99 score on a scale n=5 Participants • FAS included all participants who were randomized, received at least 1 dose of study drug, and have a baseline value and at least 1 valid postbaseline value for assessment of primary efficacy.	3.16 score on a scale n=7 Participants • FAS included all participants who were randomized, received at least 1 dose of study drug, and have a baseline value and at least 1 valid postbaseline value for assessment of primary efficacy.	2.98 score on a scale n=5 Participants • FAS included all participants who were randomized, received at least 1 dose of study drug, and have a baseline value and at least 1 valid postbaseline value for assessment of primary efficacy.	3.08 score on a scale n=4 Participants • FAS included all participants who were randomized, received at least 1 dose of study drug, and have a baseline value and at least 1 valid postbaseline value for assessment of primary efficacy.	3.03 score on a scale n=21 Participants • FAS included all participants who were randomized, received at least 1 dose of study drug, and have a baseline value and at least 1 valid postbaseline value for assessment of primary efficacy.
ANMS GCSI-DD Upper Abdominal Pain Symptom Score	1.76 score on a scale n=5 Participants • FAS included all participants who were randomized, received at least 1 dose of study drug, and have a baseline value and at least 1 valid postbaseline value for assessment of primary efficacy.	2.11 score on a scale n=7 Participants • FAS included all participants who were randomized, received at least 1 dose of study drug, and have a baseline value and at least 1 valid postbaseline value for assessment of primary efficacy.	1.77 score on a scale n=5 Participants • FAS included all participants who were randomized, received at least 1 dose of study drug, and have a baseline value and at least 1 valid postbaseline value for assessment of primary efficacy.	1.94 score on a scale n=4 Participants • FAS included all participants who were randomized, received at least 1 dose of study drug, and have a baseline value and at least 1 valid postbaseline value for assessment of primary efficacy.	1.85 score on a scale n=21 Participants • FAS included all participants who were randomized, received at least 1 dose of study drug, and have a baseline value and at least 1 valid postbaseline value for assessment of primary efficacy.
ANMS GCSI-DD Recorded Vomiting Frequency	1.41 vomiting episodes/day n=5 Participants • FAS included all participants who were randomized, received at least 1 dose of study drug, and have a baseline value and at least 1 valid postbaseline value for assessment of primary efficacy.	0.73 vomiting episodes/day n=7 Participants • FAS included all participants who were randomized, received at least 1 dose of study drug, and have a baseline value and at least 1 valid postbaseline value for assessment of primary efficacy.	1.25 vomiting episodes/day n=5 Participants • FAS included all participants who were randomized, received at least 1 dose of study drug, and have a baseline value and at least 1 valid postbaseline value for assessment of primary efficacy.	1.18 vomiting episodes/day n=4 Participants • FAS included all participants who were randomized, received at least 1 dose of study drug, and have a baseline value and at least 1 valid postbaseline value for assessment of primary efficacy.	1.23 vomiting episodes/day n=21 Participants • FAS included all participants who were randomized, received at least 1 dose of study drug, and have a baseline value and at least 1 valid postbaseline value for assessment of primary efficacy.
ANMS GCSI-DD Overall Severity of Gastroparesis Symptoms Score	2.90 score on a scale n=5 Participants • FAS included all participants who were randomized, received at least 1 dose of study drug, and have a baseline value and at least 1 valid postbaseline value for assessment of primary efficacy.	3.07 score on a scale n=7 Participants • FAS included all participants who were randomized, received at least 1 dose of study drug, and have a baseline value and at least 1 valid postbaseline value for assessment of primary efficacy.	2.86 score on a scale n=5 Participants • FAS included all participants who were randomized, received at least 1 dose of study drug, and have a baseline value and at least 1 valid postbaseline value for assessment of primary efficacy.	2.86 score on a scale n=4 Participants • FAS included all participants who were randomized, received at least 1 dose of study drug, and have a baseline value and at least 1 valid postbaseline value for assessment of primary efficacy.	2.89 score on a scale n=21 Participants • FAS included all participants who were randomized, received at least 1 dose of study drug, and have a baseline value and at least 1 valid postbaseline value for assessment of primary efficacy.
Bloating Severity Scale Score	2.86 score on a scale n=5 Participants • FAS included all participants who were randomized, received at least 1 dose of study drug, and have a baseline value and at least 1 valid postbaseline value for assessment of primary efficacy.	3.13 score on a scale n=7 Participants • FAS included all participants who were randomized, received at least 1 dose of study drug, and have a baseline value and at least 1 valid postbaseline value for assessment of primary efficacy.	2.89 score on a scale n=5 Participants • FAS included all participants who were randomized, received at least 1 dose of study drug, and have a baseline value and at least 1 valid postbaseline value for assessment of primary efficacy.	2.91 score on a scale n=4 Participants • FAS included all participants who were randomized, received at least 1 dose of study drug, and have a baseline value and at least 1 valid postbaseline value for assessment of primary efficacy.	2.91 score on a scale n=21 Participants • FAS included all participants who were randomized, received at least 1 dose of study drug, and have a baseline value and at least 1 valid postbaseline value for assessment of primary efficacy.
ANMS GCSI-DD Total Score	2.40 score on a scale n=5 Participants • FAS included all participants who were randomized, received at least 1 dose of study drug, and have a baseline value and at least 1 valid postbaseline value for assessment of primary efficacy.	2.49 score on a scale n=7 Participants • FAS included all participants who were randomized, received at least 1 dose of study drug, and have a baseline value and at least 1 valid postbaseline value for assessment of primary efficacy.	2.37 score on a scale n=5 Participants • FAS included all participants who were randomized, received at least 1 dose of study drug, and have a baseline value and at least 1 valid postbaseline value for assessment of primary efficacy.	2.41 score on a scale n=4 Participants • FAS included all participants who were randomized, received at least 1 dose of study drug, and have a baseline value and at least 1 valid postbaseline value for assessment of primary efficacy.	2.40 score on a scale n=21 Participants • FAS included all participants who were randomized, received at least 1 dose of study drug, and have a baseline value and at least 1 valid postbaseline value for assessment of primary efficacy.
PAGI-SYM Total Score	3.13 score on a scale n=5 Participants • FAS included all participants who were randomized, received at least 1 dose of study drug, and have a baseline value and at least 1 valid postbaseline value for assessment of primary efficacy.	3.33 score on a scale n=7 Participants • FAS included all participants who were randomized, received at least 1 dose of study drug, and have a baseline value and at least 1 valid postbaseline value for assessment of primary efficacy.	3.05 score on a scale n=5 Participants • FAS included all participants who were randomized, received at least 1 dose of study drug, and have a baseline value and at least 1 valid postbaseline value for assessment of primary efficacy.	3.13 score on a scale n=4 Participants • FAS included all participants who were randomized, received at least 1 dose of study drug, and have a baseline value and at least 1 valid postbaseline value for assessment of primary efficacy.	3.13 score on a scale n=21 Participants • FAS included all participants who were randomized, received at least 1 dose of study drug, and have a baseline value and at least 1 valid postbaseline value for assessment of primary efficacy.

PRIMARY outcome

Timeframe: Baseline and Week 12

Outcome measures

Outcome measures
Measure	Placebo n=73 Participants TAK-906 maleate placebo-matching capsules, orally, BID for up to 12 weeks.	TAK-906 Maleate 5 mg n=23 Participants TAK-906 maleate 5 mg, capsules, orally, BID for up to 12 weeks.	TAK-906 Maleate 25 mg n=72 Participants TAK-906 maleate 25 mg, capsules, orally, BID for up to 12 weeks.	TAK-906 Maleate 50 mg n=74 Participants TAK-906 maleate 50 mg, capsules, orally, BID for up to 12 weeks.
Change From Baseline in the American Neurogastroenterology and Motility Society Gastroparesis Cardinal Symptom Index-Daily Diary (ANMS GCSI-DD) Composite Score at Week 12 of the Treatment Period	-1.19 score on a scale Standard Error 0.120	-1.11 score on a scale Standard Error 0.219	-1.17 score on a scale Standard Error 0.120	-1.21 score on a scale Standard Error 0.116

SECONDARY outcome

Timeframe: Baseline and Week 12

ANMS GCSI-DD is a patient-reported outcome instrument for a symptom-based clinical trial endpoint in gastroparesis . The ANMS GCSI-DD composite score included score of nausea, early satiety, upper abdominal pain and postprandial fullness. The severity scores of these symptoms range from 0 (none) to 4 (very severe). The daily composite score was calculated by summing the scores on the 4 symptom items (nausea, early satiety, postprandial fullness, and upper abdominal pain) and then dividing by 4, that is the number of items within the composite score. Thus, the maximum daily composite score was (4 symptoms × maximum score 4 divided by 4) = 16/4 = 4. The ANMS GCSI-DD daily composite score ranged from 0 to 4 with higher scores reflecting greater symptom severity.

Outcome measures

Outcome measures
Measure	Placebo n=73 Participants TAK-906 maleate placebo-matching capsules, orally, BID for up to 12 weeks.	TAK-906 Maleate 5 mg n=23 Participants TAK-906 maleate 5 mg, capsules, orally, BID for up to 12 weeks.	TAK-906 Maleate 25 mg n=72 Participants TAK-906 maleate 25 mg, capsules, orally, BID for up to 12 weeks.	TAK-906 Maleate 50 mg n=74 Participants TAK-906 maleate 50 mg, capsules, orally, BID for up to 12 weeks.
Percentage of Participants With at Least 50% Reduction From Baseline in ANMS GCSI-DD Composite Score at Week 12	42.5 percentage of participants	39.1 percentage of participants	47.2 percentage of participants	41.9 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: FAS included all participants who were randomized, received at least 1 dose of study drug, and have a baseline value and at least 1 valid postbaseline value for assessment of primary efficacy. Overall number analyzed is the number of participants with data available for analysis.

ANMS GCSI-DD is a patient-reported outcome instrument for a symptom-based clinical trial endpoint in gastroparesis. The ANMS GCSI-DD assesses nausea, early satiety, postprandial fullness, and upper abdominal pain on a severity score calculated from a 5-point Likert scale. The ANMS GCSI-DD nausea symptom score ranged from 0 to 4 with higher scores reflecting greater symptom severity. The negative change from baseline indicates improvement. MMRM was used for analysis.

Outcome measures

Outcome measures
Measure	Placebo n=50 Participants TAK-906 maleate placebo-matching capsules, orally, BID for up to 12 weeks.	TAK-906 Maleate 5 mg n=15 Participants TAK-906 maleate 5 mg, capsules, orally, BID for up to 12 weeks.	TAK-906 Maleate 25 mg n=55 Participants TAK-906 maleate 25 mg, capsules, orally, BID for up to 12 weeks.	TAK-906 Maleate 50 mg n=58 Participants TAK-906 maleate 50 mg, capsules, orally, BID for up to 12 weeks.
Change From Baseline in the ANMS GCSI-DD Nausea Symptom Score at Week 12 of the Treatment Period	-1.42 score on a scale Standard Error 0.134	-1.36 score on a scale Standard Error 0.245	-1.36 score on a scale Standard Error 0.133	-1.40 score on a scale Standard Error 0.129

SECONDARY outcome

Timeframe: Baseline and Week 12

ANMS GCSI-DD is a patient-reported outcome instrument for a symptom-based clinical trial endpoint in gastroparesis. The ANMS GCSI-DD assesses nausea, early satiety, postprandial fullness, and upper abdominal pain on a severity score calculated from a 5-point Likert scale. The ANMS GCSI-DD early satiety symptom score ranged from 0 to 4 with higher scores reflecting greater symptom severity. The negative change from Baseline indicated improvement. MMRM was used for the analysis.

Outcome measures

Outcome measures
Measure	Placebo n=50 Participants TAK-906 maleate placebo-matching capsules, orally, BID for up to 12 weeks.	TAK-906 Maleate 5 mg n=15 Participants TAK-906 maleate 5 mg, capsules, orally, BID for up to 12 weeks.	TAK-906 Maleate 25 mg n=55 Participants TAK-906 maleate 25 mg, capsules, orally, BID for up to 12 weeks.	TAK-906 Maleate 50 mg n=58 Participants TAK-906 maleate 50 mg, capsules, orally, BID for up to 12 weeks.
Change From Baseline in the ANMS GCSI-DD Early Satiety Symptom Score at Week 12 of the Treatment Period	-1.26 score on a scale Standard Error 0.136	-1.25 score on a scale Standard Error 0.248	-1.17 score on a scale Standard Error 0.135	-1.33 score on a scale Standard Error 0.131

SECONDARY outcome

Timeframe: Baseline and Week 12

ANMS GCSI-DD is a patient-reported outcome instrument for a symptom-based clinical trial endpoint in gastroparesis. The ANMS GCSI-DD assesses nausea, early satiety, postprandial fullness, and upper abdominal pain on a severity score calculated from a 5-point Likert scale. The ANMS GCSI-DD postprandial fullness symptom score ranged from 0 to 4 with higher scores reflecting greater symptom severity. The negative change from baseline indicates improvement. MMRM was used for the analysis.

Outcome measures

Outcome measures
Measure	Placebo n=50 Participants TAK-906 maleate placebo-matching capsules, orally, BID for up to 12 weeks.	TAK-906 Maleate 5 mg n=15 Participants TAK-906 maleate 5 mg, capsules, orally, BID for up to 12 weeks.	TAK-906 Maleate 25 mg n=55 Participants TAK-906 maleate 25 mg, capsules, orally, BID for up to 12 weeks.	TAK-906 Maleate 50 mg n=58 Participants TAK-906 maleate 50 mg, capsules, orally, BID for up to 12 weeks.
Change From Baseline in the ANMS GCSI-DD Postprandial Fullness Symptom Score at Week 12 of the Treatment Period	-1.32 score on a scale Standard Error 0.139	-1.26 score on a scale Standard Error 0.253	-1.27 score on a scale Standard Error 0.138	-1.35 score on a scale Standard Error 0.134

SECONDARY outcome

Timeframe: Baseline and Week 12

ANMS GCSI-DD is a patient-reported outcome instrument for a symptom-based clinical trial endpoint in gastroparesis. The ANMS GCSI-DD assesses nausea, early satiety, postprandial fullness, and upper abdominal pain on a severity score calculated from a 5-point Likert scale. The ANMS GCSI-DD upper abdominal pain symptom score ranged from 0 to 4 with higher scores reflecting greater symptom severity. The negative change from baseline indicates improvement. MMRM was used for the analysis.

Outcome measures

Outcome measures
Measure	Placebo n=50 Participants TAK-906 maleate placebo-matching capsules, orally, BID for up to 12 weeks.	TAK-906 Maleate 5 mg n=15 Participants TAK-906 maleate 5 mg, capsules, orally, BID for up to 12 weeks.	TAK-906 Maleate 25 mg n=55 Participants TAK-906 maleate 25 mg, capsules, orally, BID for up to 12 weeks.	TAK-906 Maleate 50 mg n=58 Participants TAK-906 maleate 50 mg, capsules, orally, BID for up to 12 weeks.
Change From Baseline in the ANMS GCSI-DD Upper Abdominal Pain Symptom Score at Week 12 of the Treatment Period	-0.72 score on a scale Standard Error 0.118	-0.68 score on a scale Standard Error 0.214	-0.90 score on a scale Standard Error 0.117	-0.76 score on a scale Standard Error 0.114

SECONDARY outcome

Timeframe: Baseline and Week 12

Vomiting frequency was collected as the number of times a participant vomited in a 24-hour period i.e., vomiting episodes using the ANMS GCSI-DD. The daily score was averaged over 7 days. Higher scores indicate more severe symptoms. MMRM was used for the analysis.

Outcome measures

Outcome measures
Measure	Placebo n=50 Participants TAK-906 maleate placebo-matching capsules, orally, BID for up to 12 weeks.	TAK-906 Maleate 5 mg n=15 Participants TAK-906 maleate 5 mg, capsules, orally, BID for up to 12 weeks.	TAK-906 Maleate 25 mg n=55 Participants TAK-906 maleate 25 mg, capsules, orally, BID for up to 12 weeks.	TAK-906 Maleate 50 mg n=57 Participants TAK-906 maleate 50 mg, capsules, orally, BID for up to 12 weeks.
Change From Baseline in the ANMS GCSI-DD Recorded Vomiting Frequency at Week 12 of the Treatment Period	-0.71 vomiting episodes/day Standard Error 0.236	-0.44 vomiting episodes/day Standard Error 0.421	-0.48 vomiting episodes/day Standard Error 0.234	-0.63 vomiting episodes/day Standard Error 0.231

SECONDARY outcome

Timeframe: Baseline and Week 12

The overall severity of gastroparesis symptoms is the participant report of the overall severity rating of their symptoms as entered daily in the ANMS GCSI-DD and at time of visit. Severity was rated on a 0 (none) to 4 (very severe) scale. Higher score values indicated more severe symptoms. MMRM was used for the analysis.

Outcome measures

Outcome measures
Measure	Placebo n=50 Participants TAK-906 maleate placebo-matching capsules, orally, BID for up to 12 weeks.	TAK-906 Maleate 5 mg n=15 Participants TAK-906 maleate 5 mg, capsules, orally, BID for up to 12 weeks.	TAK-906 Maleate 25 mg n=55 Participants TAK-906 maleate 25 mg, capsules, orally, BID for up to 12 weeks.	TAK-906 Maleate 50 mg n=58 Participants TAK-906 maleate 50 mg, capsules, orally, BID for up to 12 weeks.
Change From Baseline in the ANMS GCSI-DD Overall Severity of Gastroparesis Symptoms Score at Week 12 of the Treatment Period	-1.20 score on a scale Standard Error 0.130	-1.02 score on a scale Standard Error 0.237	-1.22 score on a scale Standard Error 0.129	-1.25 score on a scale Standard Error 0.125

SECONDARY outcome

Timeframe: Baseline and Week 12

The bloating severity scale was scored from 0 to 4 (where 0 = no symptom and 4 = severe symptom). The daily total score can range from 0 to 4 with higher scores reflecting greater symptom severity. The negative change from baseline indicates improvement. MMRM was used for analysis.

Outcome measures

Outcome measures
Measure	Placebo n=50 Participants TAK-906 maleate placebo-matching capsules, orally, BID for up to 12 weeks.	TAK-906 Maleate 5 mg n=15 Participants TAK-906 maleate 5 mg, capsules, orally, BID for up to 12 weeks.	TAK-906 Maleate 25 mg n=55 Participants TAK-906 maleate 25 mg, capsules, orally, BID for up to 12 weeks.	TAK-906 Maleate 50 mg n=58 Participants TAK-906 maleate 50 mg, capsules, orally, BID for up to 12 weeks.
Change From Baseline in the ANMS GCI-DD Bloating Severity Scale Score at Week 12 of the Treatment Period	-1.15 score on a scale Standard Error 0.137	-1.09 score on a scale Standard Error 0.250	-1.26 score on a scale Standard Error 0.136	-1.16 score on a scale Standard Error 0.132

SECONDARY outcome

Timeframe: Baseline and Week 12

Daily total score was calculated by summing scores on each of the 5 symptom items in ANMS GCSI-DD (nausea, early satiety, postprandial fullness, upper abdominal pain and vomiting) plus the bloating severity item and then dividing by 6. When calculating total score, vomiting frequency was scored from 0 to 4 (where 0=no vomiting and 4=four or more episodes of vomiting). The daily total score can range from 0 to 4 with higher scores reflecting greater symptom severity. MMRM was used for analyses.

Outcome measures

Outcome measures
Measure	Placebo n=50 Participants TAK-906 maleate placebo-matching capsules, orally, BID for up to 12 weeks.	TAK-906 Maleate 5 mg n=15 Participants TAK-906 maleate 5 mg, capsules, orally, BID for up to 12 weeks.	TAK-906 Maleate 25 mg n=55 Participants TAK-906 maleate 25 mg, capsules, orally, BID for up to 12 weeks.	TAK-906 Maleate 50 mg n=58 Participants TAK-906 maleate 50 mg, capsules, orally, BID for up to 12 weeks.
Change From Baseline in the ANMS GCSI-DD Total Score at Week 12 of the Treatment Period	-1.10 score on a scale Standard Error 0.108	-1.00 score on a scale Standard Error 0.196	-1.09 score on a scale Standard Error 0.107	-1.11 score on a scale Standard Error 0.104

SECONDARY outcome

Timeframe: Up to 12 weeks

Symptomatic weeks are weeks with average composite symptom score assessed as \>mild \[ANMS GCSI-DD score ≥2\] during 12 weeks of treatment. Analysis of variance (ANOVA) was used for the analysis.

Outcome measures

Outcome measures
Measure	Placebo n=73 Participants TAK-906 maleate placebo-matching capsules, orally, BID for up to 12 weeks.	TAK-906 Maleate 5 mg n=23 Participants TAK-906 maleate 5 mg, capsules, orally, BID for up to 12 weeks.	TAK-906 Maleate 25 mg n=72 Participants TAK-906 maleate 25 mg, capsules, orally, BID for up to 12 weeks.	TAK-906 Maleate 50 mg n=74 Participants TAK-906 maleate 50 mg, capsules, orally, BID for up to 12 weeks.
Percentage of Symptomatic Weeks	54.89 percentage of weeks Standard Error 4.746	46.42 percentage of weeks Standard Error 8.474	50.03 percentage of weeks Standard Error 4.781	51.31 percentage of weeks Standard Error 4.714

SECONDARY outcome

Timeframe: Baseline and Week 12

The PAGI-SYM total score is defined as the mean of 6 PAGI-SYM subscale scores from 20 items. A 6-point Likert response scale, ranging from 0 (none) to 5 (very severe), is used to measure symptom severity in participants with upper GI disorders. The negative change from baseline indicates improvement. MMRM was used for analysis.

Outcome measures

Outcome measures
Measure	Placebo n=57 Participants TAK-906 maleate placebo-matching capsules, orally, BID for up to 12 weeks.	TAK-906 Maleate 5 mg n=16 Participants TAK-906 maleate 5 mg, capsules, orally, BID for up to 12 weeks.	TAK-906 Maleate 25 mg n=54 Participants TAK-906 maleate 25 mg, capsules, orally, BID for up to 12 weeks.	TAK-906 Maleate 50 mg n=60 Participants TAK-906 maleate 50 mg, capsules, orally, BID for up to 12 weeks.
Change From Baseline in the Patient Assessment of Upper Gastrointestinal Disorders-Symptom Severity Index (PAGI-SYM) Total Score at Week 12 of the Treatment Period	-1.33 score on a scale Standard Error 0.141	-1.25 score on a scale Standard Error 0.265	-1.51 score on a scale Standard Error 0.142	-1.57 score on a scale Standard Error 0.136

Adverse Events

Placebo

Serious events: 2 serious events

Other events: 0 other events

Deaths: 0 deaths

TAK-906 5 mg

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

TAK-906 25 mg

Serious events: 2 serious events

Other events: 4 other events

Deaths: 0 deaths

TAK-906 50 mg

Serious events: 2 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=73 participants at risk TAK-906 maleate placebo-matching capsules, orally, BID for up to 12 weeks.	TAK-906 5 mg n=23 participants at risk TAK-906 maleate 5 mg, capsules, orally, BID for up to 12 weeks.	TAK-906 25 mg n=72 participants at risk TAK-906 maleate 25 mg, capsules, orally, BID for up to 12 weeks.	TAK-906 50 mg n=74 participants at risk TAK-906 maleate 50 mg, capsules, orally, BID for up to 12 weeks.
Infections and infestations COVID-19 pneumonia	0.00% 0/73 • From the study start up to 30 days after end of treatment (up to approximately 16 weeks) 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. Safety data was collected for all participants evaluable for response.	0.00% 0/23 • From the study start up to 30 days after end of treatment (up to approximately 16 weeks) 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. Safety data was collected for all participants evaluable for response.	1.4% 1/72 • From the study start up to 30 days after end of treatment (up to approximately 16 weeks) 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. Safety data was collected for all participants evaluable for response.	0.00% 0/74 • From the study start up to 30 days after end of treatment (up to approximately 16 weeks) 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. Safety data was collected for all participants evaluable for response.
Skin and subcutaneous tissue disorders Diabetic foot	1.4% 1/73 • From the study start up to 30 days after end of treatment (up to approximately 16 weeks) 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. Safety data was collected for all participants evaluable for response.	0.00% 0/23 • From the study start up to 30 days after end of treatment (up to approximately 16 weeks) 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. Safety data was collected for all participants evaluable for response.	0.00% 0/72 • From the study start up to 30 days after end of treatment (up to approximately 16 weeks) 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. Safety data was collected for all participants evaluable for response.	0.00% 0/74 • From the study start up to 30 days after end of treatment (up to approximately 16 weeks) 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. Safety data was collected for all participants evaluable for response.
Metabolism and nutrition disorders Diabetic ketoacidosis	0.00% 0/73 • From the study start up to 30 days after end of treatment (up to approximately 16 weeks) 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. Safety data was collected for all participants evaluable for response.	0.00% 0/23 • From the study start up to 30 days after end of treatment (up to approximately 16 weeks) 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. Safety data was collected for all participants evaluable for response.	0.00% 0/72 • From the study start up to 30 days after end of treatment (up to approximately 16 weeks) 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. Safety data was collected for all participants evaluable for response.	1.4% 1/74 • From the study start up to 30 days after end of treatment (up to approximately 16 weeks) 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. Safety data was collected for all participants evaluable for response.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/73 • From the study start up to 30 days after end of treatment (up to approximately 16 weeks) 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. Safety data was collected for all participants evaluable for response.	0.00% 0/23 • From the study start up to 30 days after end of treatment (up to approximately 16 weeks) 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. Safety data was collected for all participants evaluable for response.	1.4% 1/72 • From the study start up to 30 days after end of treatment (up to approximately 16 weeks) 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. Safety data was collected for all participants evaluable for response.	0.00% 0/74 • From the study start up to 30 days after end of treatment (up to approximately 16 weeks) 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. Safety data was collected for all participants evaluable for response.
Vascular disorders Intermittent claudication	0.00% 0/73 • From the study start up to 30 days after end of treatment (up to approximately 16 weeks) 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. Safety data was collected for all participants evaluable for response.	0.00% 0/23 • From the study start up to 30 days after end of treatment (up to approximately 16 weeks) 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. Safety data was collected for all participants evaluable for response.	0.00% 0/72 • From the study start up to 30 days after end of treatment (up to approximately 16 weeks) 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. Safety data was collected for all participants evaluable for response.	1.4% 1/74 • From the study start up to 30 days after end of treatment (up to approximately 16 weeks) 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. Safety data was collected for all participants evaluable for response.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oesophageal carcinoma	1.4% 1/73 • From the study start up to 30 days after end of treatment (up to approximately 16 weeks) 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. Safety data was collected for all participants evaluable for response.	0.00% 0/23 • From the study start up to 30 days after end of treatment (up to approximately 16 weeks) 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. Safety data was collected for all participants evaluable for response.	0.00% 0/72 • From the study start up to 30 days after end of treatment (up to approximately 16 weeks) 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. Safety data was collected for all participants evaluable for response.	0.00% 0/74 • From the study start up to 30 days after end of treatment (up to approximately 16 weeks) 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. Safety data was collected for all participants evaluable for response.

Other adverse events

Other adverse events
Measure	Placebo n=73 participants at risk TAK-906 maleate placebo-matching capsules, orally, BID for up to 12 weeks.	TAK-906 5 mg n=23 participants at risk TAK-906 maleate 5 mg, capsules, orally, BID for up to 12 weeks.	TAK-906 25 mg n=72 participants at risk TAK-906 maleate 25 mg, capsules, orally, BID for up to 12 weeks.	TAK-906 50 mg n=74 participants at risk TAK-906 maleate 50 mg, capsules, orally, BID for up to 12 weeks.
Nervous system disorders Headache	0.00% 0/73 • From the study start up to 30 days after end of treatment (up to approximately 16 weeks) 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. Safety data was collected for all participants evaluable for response.	0.00% 0/23 • From the study start up to 30 days after end of treatment (up to approximately 16 weeks) 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. Safety data was collected for all participants evaluable for response.	5.6% 4/72 • From the study start up to 30 days after end of treatment (up to approximately 16 weeks) 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. Safety data was collected for all participants evaluable for response.	0.00% 0/74 • From the study start up to 30 days after end of treatment (up to approximately 16 weeks) 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. Safety data was collected for all participants evaluable for response.
Gastrointestinal disorders Nausea	0.00% 0/73 • From the study start up to 30 days after end of treatment (up to approximately 16 weeks) 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. Safety data was collected for all participants evaluable for response.	0.00% 0/23 • From the study start up to 30 days after end of treatment (up to approximately 16 weeks) 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. Safety data was collected for all participants evaluable for response.	0.00% 0/72 • From the study start up to 30 days after end of treatment (up to approximately 16 weeks) 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. Safety data was collected for all participants evaluable for response.	5.4% 4/74 • From the study start up to 30 days after end of treatment (up to approximately 16 weeks) 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. Safety data was collected for all participants evaluable for response.
Infections and infestations Upper respiratory tract infection	0.00% 0/73 • From the study start up to 30 days after end of treatment (up to approximately 16 weeks) 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. Safety data was collected for all participants evaluable for response.	8.7% 2/23 • From the study start up to 30 days after end of treatment (up to approximately 16 weeks) 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. Safety data was collected for all participants evaluable for response.	0.00% 0/72 • From the study start up to 30 days after end of treatment (up to approximately 16 weeks) 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. Safety data was collected for all participants evaluable for response.	0.00% 0/74 • From the study start up to 30 days after end of treatment (up to approximately 16 weeks) 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. Safety data was collected for all participants evaluable for response.

Additional Information

Study Director

Takeda

Phone: +1-877-825-3327

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER