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Clinical Trial Results:
A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Phase 2b Study to Evaluate the Efficacy and Safety of Twice-Daily Oral Administration of a Peripherally Acting Dopamine Receptor D2/D3 Antagonist, TAK-906 for the Treatment of Adult Subjects With Symptomatic Idiopathic or Diabetic Gastroparesis

Summary
EudraCT number	2018-001275-21
Trial protocol	BE PL IT
Global end of trial date	15 Jul 2021

Results information
Results version number	v1(current)
This version publication date	30 Jun 2022
First version publication date	30 Jun 2022
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

TAK-906-2002

ISRCTN number

US NCT number

NCT03544229

WHO universal trial number (UTN)

U1111-1211-2779

Sponsor organisation name

Takeda

Sponsor organisation address

95 Hayden Avenue, Lexington, United States, MA 02421

Public contact

Study Director, Takeda, TrialDisclosures@takeda.com

Scientific contact

Study Director, Takeda, TrialDisclosures@takeda.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

15 Jul 2021

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

15 Jul 2021

Was the trial ended prematurely?

Main objective of the trial

The main objective of this trial is to assess the efficacy of treatment with various dose levels of TAK-906 in adult participants with gastroparesis compared with placebo during 12 weeks of treatment.

Protection of trial subjects

All study participants were required to read and sign an Informed Consent Form.

Background therapy

Evidence for comparator

Actual start date of recruitment

17 Oct 2018

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Japan: 35

Country: Number of subjects enrolled

Belgium: 9

Country: Number of subjects enrolled

Poland: 6

Country: Number of subjects enrolled

United States: 192

Worldwide total number of subjects

242

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

167

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

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.

Screening details

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.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Data analyst, Carer

Are arms mutually exclusive

Placebo

Arm description

TAK-906 maleate placebo-matching capsules, orally, twice daily (BID) for up to 12 weeks.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

TAK-906 maleate placebo-matching capsules.

TAK-906 Maleate 5 mg

Arm description

TAK-906 maleate 5 mg, capsules, orally, BID for up to 12 weeks.

Arm type

Experimental

Investigational medicinal product name

TAK-906 Maleate

Investigational medicinal product code

Other name

TAK-906

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

TAK-906 maleate 5 mg capsules.

TAK-906 Maleate 25 mg

Arm description

TAK-906 maleate 25 mg, capsules, orally, BID for up to 12 weeks.

Arm type

Experimental

Investigational medicinal product name

TAK-906 Maleate

Investigational medicinal product code

Other name

TAK-906

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

TAK-906 maleate 25 mg capsules.

TAK-906 Maleate 50 mg

Arm description

TAK-906 maleate 50 mg, capsules, orally, BID for up to 12 weeks.

Arm type

Experimental

Investigational medicinal product name

TAK-906 Maleate

Investigational medicinal product code

Other name

TAK-906

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

TAK-906 maleate 50 mg capsules.

Number of subjects in period 1	Placebo	TAK-906 Maleate 5 mg	TAK-906 Maleate 25 mg	TAK-906 Maleate 50 mg
Started	73	23	72	74
Completed	67	21	67	72
Not completed	6	2	5	2
Adverse event, non-fatal	1	-	1	-
Voluntary Withdrawal	2	1	3	-
Protocol Deviation	-	-	1	-
Lost to follow-up	3	-	-	2
Lack of efficacy	-	1	-	-

Baseline characteristics

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Reporting group title

Placebo

Reporting group description

TAK-906 maleate placebo-matching capsules, orally, twice daily (BID) for up to 12 weeks.

Reporting group title

TAK-906 Maleate 5 mg

Reporting group description

TAK-906 maleate 5 mg, capsules, orally, BID for up to 12 weeks.

Reporting group title

TAK-906 Maleate 25 mg

Reporting group description

TAK-906 maleate 25 mg, capsules, orally, BID for up to 12 weeks.

Reporting group title

TAK-906 Maleate 50 mg

Reporting group description

TAK-906 maleate 50 mg, capsules, orally, BID for up to 12 weeks.

Reporting group values	Placebo	TAK-906 Maleate 5 mg	TAK-906 Maleate 25 mg	TAK-906 Maleate 50 mg	Total
Number of subjects	73	23	72	74
Age Categorical
Units: Subjects
Age continuous
Units: years
arithmetic mean (standard deviation)	57.1 ± 14.22	56.3 ± 14.32	56.4 ± 13.31	53.4 ± 15.09	-
Gender categorical
Units: Subjects
Male	19	4	11	25	59
Female	54	19	61	49	183
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	30	14	38	28	110
Not Hispanic or Latino	42	9	34	45	130
Unknown or Not Reported	1	0	0	1	2
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	0	0	0	1	1
Asian	8	4	12	15	39
Native Hawaiian or Other Pacific Islander	0	0	0	0	0
Black or African American	10	1	4	11	26
White	54	18	55	45	172
More than one race	0	0	0	0	0
Unknown or Not Reported	1	0	1	2	4
Region of Enrollment
Units: Subjects
Belgium	3	0	3	3	9
Japan	8	4	10	13	35
Poland	2	0	2	2	6
United States	60	19	57	56	192
Smoking Classification
Units: Subjects
Participant has Never Smoked	51	18	57	54	180
Participant is a Current Smoker	10	1	7	5	23
Participant is an Ex-smoker	12	4	8	15	39
Height
Units: centimetres (cm)
arithmetic mean (standard deviation)	164.17 ± 10.238	164.43 ± 9.178	161.32 ± 7.313	166.12 ± 8.841	-
Weight
Units: kilograms (kg)
arithmetic mean (standard deviation)	79.35 ± 16.383	82.62 ± 17.021	71.97 ± 16.261	78.77 ± 15.201	-
Body Mass Index (BMI)
BMI was calculated as weight (kg) divided by square of height (m^2).
Units: kg/m^2
arithmetic mean (standard deviation)	29.35 ± 5.003	30.48 ± 5.606	27.61 ± 5.835	28.52 ± 4.934	-
ANMS GCSI-DD Composite Score
American Neurogastroenterology and Motility Society Gastroparesis Cardinal Symptom Index-Daily Diary(ANMS GCSI-DD): patient-reported outcome instrument for symptom-based clinical trial endpoint in gastroparesis. The daily score was calculated by summing scores on 4 symptoms(nausea, early satiety, postprandial fullness, and upper abdominal pain)/4 (number of items within score), ranged from 0 to 4 with higher scores=symptom severity. FAS=all participants who were randomized, received at least 1 dose of study drug, and have baseline and at least 1 valid postbaseline value for assessment.
Units: score on a scale
arithmetic mean (full range (min-max))	2.59 (2.0 to 4.0)	2.77 (2.0 to 3.8)	2.57 (2.0 to 4.0)	2.64 (2.0 to 4.0)	-
ANMS GCSI-DD Nausea Symptom Score at Week 12 of the Treatment Period
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. FAS: 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.
Units: score on a scale
arithmetic mean (full range (min-max))	2.80 (1.6 to 4.0)	2.85 (1.7 to 4.0)	2.70 (1.6 to 4.0)	2.72 (1.9 to 4.0)	-
ANMS GCSI-DD Early Satiety Symptom Score at Week 12 of the Treatment Period
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. 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.
Units: score on a scale
arithmetic mean (full range (min-max))	2.80 (1.3 to 4.0)	2.97 (2.0 to 4.0)	2.82 (1.3 to 4.0)	2.82 (1.9 to 4.0)	-
ANMS GCSI-DD Postprandial Fullness Symptom Score at Week 12 of the Treatment Period
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. 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.
Units: score on a scale
arithmetic mean (full range (min-max))	2.99 (2.0 to 4.0)	3.16 (2.1 to 4.0)	2.98 (2.0 to 4.0)	3.08 (2.0 to 4.0)	-
ANMS GCSI-DD Upper Abdominal Pain Symptom Score at Week 12 of the Treatment Period
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. 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.
Units: score on a scale
arithmetic mean (full range (min-max))	1.76 (0.0 to 4.0)	2.11 (0.1 to 4.0)	1.77 (0.0 to 4.0)	1.94 (0.0 to 3.9)	-
ANMS GCSI-DD Recorded Vomiting Frequency at Week 12 of the Treatment Period
The vomiting frequency was scored from 0 to 4 (where 0 = no vomiting and 4 = four or more episodes of vomiting). The maximum core symptom score could be (5 symptoms × maximum score 4 divided by 5) = 20/5 = 4. The weekly recorded vomiting frequency for each postbaseline week was the average of the 7 daily scores within the targeted week relative to the first dose date. The ANMS GCSI-DD daily vomiting frequency score ranged from 0 to 4 with higher scores reflecting greater symptom severity.
Units: score on a scale
arithmetic mean (full range (min-max))	1.41 (0.0 to 11.4)	0.73 (0.0 to 1.9)	1.25 (0.0 to 7.9)	1.18 (0.0 to 11.0)	-
ANMS GCSI-DD Overall Severity of Gastroparesis Symptoms Score in Treatment Period
The maximum total symptom score could be (6 symptoms × maximum score 4 divided by 6) = 24/6 = 4. The ANMS GCSI-DD overall severity of gastroparesis symptoms score can range from 0 to 4 with higher scores reflecting greater symptom severity. 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.
Units: score on a scale
arithmetic mean (full range (min-max))	2.90 (2.0 to 4.0)	3.07 (2.0 to 4.0)	2.86 (1.4 to 4.0)	2.86 (1.4 to 4.0)	-
Bloating Severity Scale Score at Week 12 of the Treatment Period
The bloating severity scale was scored from 0 to 4 (where 0 = no symptom and 4 = severe symptom). The maximum total symptom score could be (6 symptoms × maximum score 4 divided by 6)= 24/6 = 4. The ANMS GCSI-DD daily total score can range from 0 to 4 with higher scores reflecting greater symptom severity. FAS: 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.
Units: score on a scale
arithmetic mean (full range (min-max))	2.86 (2.0 to 4.0)	3.13 (2.0 to 4.0)	2.89 (1.1 to 4.0)	2.91 (1.7 to 4.0)	-
ANMS GCSI-DD Total Score at Week 12 of the Treatment Period
The daily total score is calculated by summing the 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. The maximum total symptom score could be (6 symptoms × maximum score 4 divided by 6) = 24/6 = 4. The ANMS GCSI-DD daily total score can range from 0 to 4 with higher scores reflecting greater symptom severity. FAS population.
Units: score on a scale
arithmetic mean (full range (min-max))	2.40 (1.7 to 3.6)	2.49 (1.7 to 3.4)	2.37 (1.5 to 4.0)	2.41 (1.7 to 3.8)	-
PAGI-SYM Total Score at Week 12 of the Treatment Period
The patient assessment of upper gastrointestinal disorders-symptom severity index (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 patients with upper GI disorders. 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.
Units: score on a scale
arithmetic mean (full range (min-max))	3.13 (0.1 to 4.9)	3.33 (2.1 to 4.7)	3.05 (1.7 to 4.7)	3.14 (1.0 to 4.9)	-

End points

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Reporting group title

Placebo

Reporting group description

TAK-906 maleate placebo-matching capsules, orally, twice daily (BID) for up to 12 weeks.

Reporting group title

TAK-906 Maleate 5 mg

Reporting group description

TAK-906 maleate 5 mg, capsules, orally, BID for up to 12 weeks.

Reporting group title

TAK-906 Maleate 25 mg

Reporting group description

TAK-906 maleate 25 mg, capsules, orally, BID for up to 12 weeks.

Reporting group title

TAK-906 Maleate 50 mg

Reporting group description

TAK-906 maleate 50 mg, capsules, orally, BID for up to 12 weeks.

Primary: 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

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End point title

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

End point description

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

End point type

Primary

End point timeframe

Baseline and Week 12

End point values	Placebo	TAK-906 Maleate 5 mg	TAK-906 Maleate 25 mg	TAK-906 Maleate 50 mg
Number of subjects analysed	50	15	55	58
Units: score on a scale
least squares mean (standard error)	-1.19 ± 0.120	-1.11 ± 0.219	-1.17 ± 0.120	-1.21 ± 0.116

ANMS GCSI-DD Composite Score

Comparison groups

Placebo v TAK-906 Maleate 5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[1]

P-value

= 0.618 ^[2]

Method

MMRM

Parameter type

Least-Squares Mean Difference

Point estimate

0.08

Confidence interval

level

90%

sides

2-sided

lower limit

-0.34

upper limit

0.49

Variability estimate

Standard error of the mean

Dispersion value

0.25

Notes
[1] - Mixed-effects Model for Repeated Measures (MMRM) included week, treatment, participant disease population (DG/IG), treatment-by-week interaction as fixed effects, baseline and baseline score-by-week interaction as covariates, with an unstructured working covariance matrix as default.
[2] - 1-sided p-values were obtained using MMRM Model. It was based on the one-sided alternative hypothesis testing that the treatment difference (TAK-906 - Placebo) in ANMS GCSI-DD composite score was <0.

ANMS GCSI-DD Composite Score

Comparison groups

Placebo v TAK-906 Maleate 25 mg

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

superiority ^[3]

P-value

= 0.533 ^[4]

Method

MMRM

Parameter type

Least Square Mean Difference

Point estimate

0.01

Confidence interval

level

90%

sides

2-sided

lower limit

-0.27

upper limit

0.29

Variability estimate

Standard error of the mean

Dispersion value

0.17

Notes
[3] - MMRM model included week, treatment, participant disease population (DG/IG), treatment-by-week interaction as fixed effects, baseline and baseline score-by-week interaction as covariates, with an unstructured working covariance matrix as default.
[4] - 1-sided p-values were obtained using MMRM Model. It was based on the one-sided alternative hypothesis testing that the treatment difference (TAK-906 - Placebo) in ANMS GCSI-DD composite score was <0.

ANMS GCSI-DD Composite Score

Comparison groups

Placebo v TAK-906 Maleate 50 mg

Number of subjects included in analysis

108

Analysis specification

Pre-specified

Analysis type

superiority ^[5]

P-value

= 0.447 ^[6]

Method

MMRM

Parameter type

Least-Squares Mean Difference

Point estimate

-0.02

Confidence interval

level

90%

sides

2-sided

lower limit

-0.3

upper limit

0.25

Variability estimate

Standard error of the mean

Dispersion value

0.167

Notes
[5] - MMRM model included week, treatment, participant disease population (DG/IG), treatment-by-week interaction as fixed effects, baseline and baseline score-by-week interaction as covariates, with an unstructured working covariance matrix as default.
[6] - 1-sided p-values were obtained using MMRM Model. It was based on the one-sided alternative hypothesis testing that the treatment difference (TAK-906 - Placebo) in ANMS GCSI-DD composite score was <0.

Secondary: Percentage of Participants with at Least 50% Reduction from Baseline in ANMS GCSI-DD Composite Score at Week 12

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End point title

Percentage of Participants with at Least 50% Reduction from Baseline in ANMS GCSI-DD Composite Score at Week 12

End point description

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. 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.

End point type

Secondary

End point timeframe

Baseline and Week 12

End point values	Placebo	TAK-906 Maleate 5 mg	TAK-906 Maleate 25 mg	TAK-906 Maleate 50 mg
Number of subjects analysed	73	23	72	74
Units: percentage of participants
number (not applicable)	42.5	39.1	47.2	41.9

Statistical Analysis: At Least 50% Reduction

Comparison groups

Placebo v TAK-906 Maleate 5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[7]

P-value

= 0.607

Method

Logistic Regression

Parameter type

Odds ratio (OR)

Point estimate

0.87

Confidence interval

level

90%

sides

2-sided

lower limit

0.39

upper limit

1.96

Notes
[7] - Comparisons of TAK-906 to Placebo was based on logistic regression with at least 50% reduction of participants from baseline in weekly composite score with baseline composite score, disease population at randomization, and treatment as covariates.

Statistical Analysis: At Least 50% Reduction

Comparison groups

Placebo v TAK-906 Maleate 25 mg

Number of subjects included in analysis

145

Analysis specification

Pre-specified

Analysis type

superiority ^[8]

P-value

= 0.283

Method

Logistic Regression

Parameter type

Odds ratio (OR)

Point estimate

1.21

Confidence interval

level

90%

sides

2-sided

lower limit

0.7

upper limit

2.1

Notes
[8] - Comparisons of TAK-906 to Placebo was based on logistic regression with at least 50% reduction of participants from baseline in weekly composite score with baseline composite score, disease population at randomization, and treatment as covariates.

Statistical Analysis: At Least 50% Reduction

Comparison groups

Placebo v TAK-906 Maleate 50 mg

Number of subjects included in analysis

147

Analysis specification

Pre-specified

Analysis type

superiority ^[9]

P-value

= 0.527

Method

Logistic Regression

Parameter type

Odds ratio (OR)

Point estimate

0.98

Confidence interval

level

90%

sides

2-sided

lower limit

0.56

upper limit

1.69

Notes
[9] - Comparisons of TAK-906 to Placebo was based on logistic regression with at least 50% reduction of participants from baseline in weekly composite score with baseline composite score, disease population at randomization, and treatment as covariates.

Secondary: Change from Baseline in the ANMS GCSI-DD Nausea Symptom Score at Week 12 of the Treatment Period

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End point title

Change from Baseline in the ANMS GCSI-DD Nausea Symptom Score at Week 12 of the Treatment Period

End point description

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. Negative change from baseline indicates improvement. MMRM was used for analyses. 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. Number analysed is the number of participants with data available for analysis.

End point type

Secondary

End point timeframe

Baseline and Week 12

End point values	Placebo	TAK-906 Maleate 5 mg	TAK-906 Maleate 25 mg	TAK-906 Maleate 50 mg
Number of subjects analysed	50	15	55	58
Units: score on a scale
least squares mean (standard error)	-1.42 ± 0.134	-1.36 ± 0.245	-1.36 ± 0.133	-1.40 ± 0.129

ANMS GCSI-DD Nausea Symptom Score

Comparison groups

Placebo v TAK-906 Maleate 5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[10]

P-value

= 0.584 ^[11]

Method

MMRM

Parameter type

Least-Squares Mean Difference

Point estimate

0.06

Confidence interval

level

90%

sides

2-sided

lower limit

-0.4

upper limit

0.52

Variability estimate

Standard error of the mean

Dispersion value

0.279

Notes
[10] - MMRM model included week, treatment, participant disease population (DG/IG), treatment-by-week interaction as fixed effects, baseline and baseline score-by-week interaction as covariates, with an unstructured working covariance matrix as default.
[11] - 1-sided p-values were obtained using MMRM Model. It was based on the one-sided alternative hypothesis testing that the treatment difference (TAK-906 - Placebo) in ANMS GCSI-DD nausea symptom score was <0.

ANMS GCSI-DD Nausea Symptom Score

Comparison groups

Placebo v TAK-906 Maleate 25 mg

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

superiority ^[12]

P-value

= 0.625 ^[13]

Method

MMRM

Parameter type

Least-Squares Mean Difference

Point estimate

0.06

Confidence interval

level

90%

sides

2-sided

lower limit

-0.25

upper limit

0.37

Variability estimate

Standard error of the mean

Dispersion value

0.189

Notes
[12] - MMRM model included week, treatment, participant disease population (DG/IG), treatment-by-week interaction as fixed effects, baseline and baseline score-by-week interaction as covariates, with an unstructured working covariance matrix as default.
[13] - 1-sided p-values were obtained using MMRM Model. It was based on the one-sided alternative hypothesis testing that the treatment difference (TAK-906 - Placebo) in ANMS GCSI-DD nausea symptom score was <0.

ANMS GCSI-DD Nausea Symptom Score

Comparison groups

Placebo v TAK-906 Maleate 50 mg

Number of subjects included in analysis

108

Analysis specification

Pre-specified

Analysis type

superiority ^[14]

P-value

= 0.54

Method

MMRM

Parameter type

Least-Squares Mean Difference

Point estimate

0.02

Confidence interval

level

90%

sides

2-sided

lower limit

-0.29

upper limit

0.33

Variability estimate

Standard error of the mean

Dispersion value

0.187

Notes
[14] - MMRM model included week, treatment, participant disease population (DG/IG), treatment-by-week interaction as fixed effects, baseline and baseline score-by-week interaction as covariates, with an unstructured working covariance matrix as default.

Secondary: Change from Baseline in the ANMS GCSI-DD Early Satiety Symptom Score at Week 12 of the Treatment Period

Top of page

End point title

Change from Baseline in the ANMS GCSI-DD Early Satiety Symptom Score at Week 12 of the Treatment Period

End point description

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. 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. Number analysed is the number of participants with data available for analysis.

End point type

Secondary

End point timeframe

Baseline and Week 12

End point values	Placebo	TAK-906 Maleate 5 mg	TAK-906 Maleate 25 mg	TAK-906 Maleate 50 mg
Number of subjects analysed	50	15	55	58
Units: score on a scale
least squares mean (standard error)	-1.26 ± 0.136	-1.25 ± 0.248	-1.17 ± 0.135	-1.33 ± 0.131

ANMS GCSI-DD Early Satiety Symptom Score

Comparison groups

Placebo v TAK-906 Maleate 5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[15]

P-value

= 0.51 ^[16]

Method

MMRM

Parameter type

Least-Squares Mean Difference

Point estimate

0.01

Confidence interval

level

90%

sides

2-sided

lower limit

-0.46

upper limit

0.47

Variability estimate

Standard error of the mean

Dispersion value

0.283

Notes
[15] - MMRM model included week, treatment, participant disease population (DG/IG), treatment-by-week interaction as fixed effects, baseline and baseline score-by-week interaction as covariates, with an unstructured working covariance matrix as default.
[16] - 1-sided p-values were obtained using MMRM Model. It was based on the one-sided alternative hypothesis testing that the treatment difference (TAK-906 - Placebo) in ANMS GCSI-DD early satiety symptom score was <0.

ANMS GCSI-DD Early Satiety Symptom Score

Comparison groups

Placebo v TAK-906 Maleate 25 mg

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

superiority ^[17]

P-value

= 0.674 ^[18]

Method

MMRM

Parameter type

Least-Squares Mean Difference

Point estimate

0.09

Confidence interval

level

90%

sides

2-sided

lower limit

-0.23

upper limit

0.4

Variability estimate

Standard error of the mean

Dispersion value

0.192

Notes
[17] - MMRM model included week, treatment, participant disease population (DG/IG), treatment-by-week interaction as fixed effects, baseline and baseline score-by-week interaction as covariates, with an unstructured working covariance matrix as default.
[18] - 1-sided p-values were obtained using MMRM Model. It was based on the one-sided alternative hypothesis testing that the treatment difference (TAK-906 - Placebo) in ANMS GCSI-DD early satiety symptom score was <0.

ANMS GCSI-DD Early Satiety Symptom Score

Comparison groups

Placebo v TAK-906 Maleate 50 mg

Number of subjects included in analysis

108

Analysis specification

Pre-specified

Analysis type

superiority ^[19]

P-value

= 0.367 ^[20]

Method

MMRM

Parameter type

Least-Squares Mean Difference

Point estimate

-0.06

Confidence interval

level

90%

sides

2-sided

lower limit

-0.38

upper limit

0.25

Variability estimate

Standard error of the mean

Dispersion value

0.189

Notes
[19] - MMRM model included week, treatment, participant disease population (DG/IG), treatment-by-week interaction as fixed effects, baseline and baseline score-by-week interaction as covariates, with an unstructured working covariance matrix as default.
[20] - 1-sided p-values were obtained using MMRM Model. It was based on the one-sided alternative hypothesis testing that the treatment difference (TAK-906 - Placebo) in ANMS GCSI-DD early satiety symptom score was <0.

Secondary: Change from Baseline in the ANMS GCSI-DD Postprandial Fullness Symptom Score at Week 12 of the Treatment Period

Top of page

End point title

Change from Baseline in the ANMS GCSI-DD Postprandial Fullness Symptom Score at Week 12 of the Treatment Period

End point description

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. 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. Number analysed is the number of participants with data available for analysis.

End point type

Secondary

End point timeframe

Baseline and Week 12

End point values	Placebo	TAK-906 Maleate 5 mg	TAK-906 Maleate 25 mg	TAK-906 Maleate 50 mg
Number of subjects analysed	50	15	55	58
Units: score on a scale
least squares mean (standard error)	-1.32 ± 0.139	-1.26 ± 0.253	-1.27 ± 0.138	-1.35 ± 0.134

ANMS GCSI-DD Postprandial Fullness Symptom Score

Comparison groups

Placebo v TAK-906 Maleate 5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[21]

P-value

= 0.587 ^[22]

Method

MMRM

Parameter type

Least-Squares Mean Difference

Point estimate

0.06

Confidence interval

level

90%

sides

2-sided

lower limit

-0.41

upper limit

0.54

Variability estimate

Standard error of the mean

Dispersion value

0.289

Notes
[21] - MMRM model included week, treatment, participant disease population (DG/IG), treatment-by-week interaction as fixed effects, baseline and baseline score-by-week interaction as covariates, with an unstructured working covariance matrix as default.
[22] - 1-sided p-values were obtained using MMRM Model. It was based on the one-sided alternative hypothesis testing that the treatment difference (TAK-906 - Placebo) in ANMS GCSI-DD postprandial fullness symptom score was <0.

ANMS GCSI-DD Postprandial Fullness Symptom Score

Comparison groups

Placebo v TAK-906 Maleate 25 mg

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

superiority ^[23]

P-value

= 0.6 ^[24]

Method

MMRM

Parameter type

Least-Squares Mean Difference

Point estimate

0.05

Confidence interval

level

90%

sides

2-sided

lower limit

-0.27

upper limit

0.37

Variability estimate

Standard error of the mean

Dispersion value

0.196

Notes
[23] - MMRM model included week, treatment, participant disease population (DG/IG), treatment-by-week interaction as fixed effects, baseline and baseline score-by-week interaction as covariates, with an unstructured working covariance matrix as default.
[24] - 1-sided p-values were obtained using MMRM Model. It was based on the one-sided alternative hypothesis testing that the treatment difference (TAK-906 - Placebo) in ANMS GCSI-DD postprandial fullness symptom score was <0.

ANMS GCSI-DD Postprandial Fullness Symptom Score

Comparison groups

Placebo v TAK-906 Maleate 50 mg

Number of subjects included in analysis

108

Analysis specification

Pre-specified

Analysis type

superiority ^[25]

P-value

= 0.446 ^[26]

Method

MMRM

Parameter type

Least-Squares Mean Difference

Point estimate

-0.03

Confidence interval

level

90%

sides

2-sided

lower limit

-0.34

upper limit

0.29

Variability estimate

Standard error of the mean

Dispersion value

0.193

Notes
[25] - MMRM model included week, treatment, participant disease population (DG/IG), treatment-by-week interaction as fixed effects, baseline and baseline score-by-week interaction as covariates, with an unstructured working covariance matrix as default.
[26] - 1-sided p-values were obtained using MMRM Model. It was based on the one-sided alternative hypothesis testing that the treatment difference (TAK-906 - Placebo) in ANMS GCSI-DD postprandial fullness symptom score was <0.

Secondary: Change from Baseline in the ANMS GCSI-DD Upper Abdominal Pain Symptom Score at Week 12 of the Treatment Period

Top of page

End point title

Change from Baseline in the ANMS GCSI-DD Upper Abdominal Pain Symptom Score at Week 12 of the Treatment Period

End point description

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. 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. Number analysed is the number of participants with data available for analysis.

End point type

Secondary

End point timeframe

Baseline and Week 12

End point values	Placebo	TAK-906 Maleate 5 mg	TAK-906 Maleate 25 mg	TAK-906 Maleate 50 mg
Number of subjects analysed	50	15	55	58
Units: score on a scale
least squares mean (standard error)	-0.72 ± 0.118	-0.68 ± 0.214	-0.90 ± 0.117	-0.76 ± 0.114

ANMS GCSI-DD Upper Abdominal Pain Symptom Score

Comparison groups

Placebo v TAK-906 Maleate 5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[27]

P-value

= 0.562 ^[28]

Method

MMRM

Parameter type

Least-Squares Mean Difference

Point estimate

0.04

Confidence interval

level

90%

sides

2-sided

lower limit

-0.37

upper limit

0.44

Variability estimate

Standard error of the mean

Dispersion value

0.245

Notes
[27] - MMRM model included week, treatment, participant disease population (DG/IG), treatment-by-week interaction as fixed effects, baseline and baseline score-by-week interaction as covariates, with an unstructured working covariance matrix as default.
[28] - 1-sided p-values were obtained using MMRM Model. It was based on the one-sided alternative hypothesis testing that the treatment difference (TAK-906 - Placebo) in ANMS GCSI-DD upper abdominal pain symptom score was <0.

ANMS GCSI-DD Upper Abdominal Pain Symptom Score

Comparison groups

Placebo v TAK-906 Maleate 25 mg

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

superiority ^[29]

P-value

= 0.138 ^[30]

Method

MMRM

Parameter type

Least-Squares Mean Difference

Point estimate

-0.18

Confidence interval

level

90%

sides

2-sided

lower limit

-0.46

upper limit

0.09

Variability estimate

Standard error of the mean

Dispersion value

0.166

Notes
[29] - MMRM model included week, treatment, participant disease population (DG/IG), treatment-by-week interaction as fixed effects, baseline and baseline score-by-week interaction as covariates, with an unstructured working covariance matrix as default.
[30] - 1-sided p-values were obtained using MMRM Model. It was based on the one-sided alternative hypothesis testing that the treatment difference (TAK-906 - Placebo) in ANMS GCSI-DD upper abdominal pain symptom score was <0.

ANMS GCSI-DD Upper Abdominal Pain Symptom Score

Comparison groups

Placebo v TAK-906 Maleate 50 mg

Number of subjects included in analysis

108

Analysis specification

Pre-specified

Analysis type

superiority ^[31]

P-value

= 0.394 ^[32]

Method

MMRM

Parameter type

Least-Squares Mean Difference

Point estimate

-0.04

Confidence interval

level

90%

sides

2-sided

lower limit

-0.32

upper limit

0.23

Variability estimate

Standard error of the mean

Dispersion value

0.164

Notes
[31] - MMRM model included week, treatment, participant disease population (DG/IG), treatment-by-week interaction as fixed effects, baseline and baseline score-by-week interaction as covariates, with an unstructured working covariance matrix as default.
[32] - 1-sided p-values were obtained using MMRM Model. It was based on the one-sided alternative hypothesis testing that the treatment difference (TAK-906 - Placebo) in ANMS GCSI-DD upper abdominal pain symptom score was <0.

Secondary: Change from Baseline in the ANMS GCSI-DD Recorded Vomiting Frequency at Week 12 of the Treatment Period

Top of page

End point title

Change from Baseline in the ANMS GCSI-DD Recorded Vomiting Frequency at Week 12 of the Treatment Period

End point description

ANMS GCSI-DD is a patient-reported outcome instrument for a symptom-based clinical trial endpoint in gastroparesis. The vomiting frequency was scored from 0 to 4 (where 0 = no vomiting and 4 = four or more episodes of vomiting). The maximum core symptom score could be (5 symptoms × maximum score 4 divided by 5) = 20/5 = 4. The weekly recorded vomiting frequency for each postbaseline week was the average of the 7 daily scores within the targeted week relative to the first dose date. The ANMS GCSI-DD daily vomiting frequency 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. FAS: 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. Number analysed is the number of participants with data available for analysis.

End point type

Secondary

End point timeframe

Baseline and Week 12

End point values	Placebo	TAK-906 Maleate 5 mg	TAK-906 Maleate 25 mg	TAK-906 Maleate 50 mg
Number of subjects analysed	50	15	55	57
Units: score on a scale
least squares mean (standard error)	-0.71 ± 0.236	-0.44 ± 0.421	-0.48 ± 0.234	-0.63 ± 0.231

ANMS GCSI-DD Recorded Vomiting Frequency

Statistical analysis description

ANMS

Comparison groups

Placebo v TAK-906 Maleate 5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[33]

P-value

= 0.709

Method

MMRM

Parameter type

Least-Squares Mean Difference

Point estimate

0.27

Confidence interval

level

90%

sides

2-sided

lower limit

-0.53

upper limit

1.07

Variability estimate

Standard error of the mean

Dispersion value

0.484

Notes
[33] - MMRM model included week, treatment, participant disease population (DG/IG), treatment-by-week interaction as fixed effects, baseline and baseline score-by-week interaction as covariates, with an unstructured working covariance matrix as default.

ANMS GCSI-DD Recorded Vomiting Frequency

Comparison groups

Placebo v TAK-906 Maleate 25 mg

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

superiority ^[34]

P-value

= 0.76 ^[35]

Method

MMRM

Parameter type

Least-Sqaures Mean Difference

Point estimate

0.24

Confidence interval

level

90%

sides

2-sided

lower limit

-0.31

upper limit

0.78

Variability estimate

Standard error of the mean

Dispersion value

0.332

Notes
[34] - MMRM model included week, treatment, participant disease population (DG/IG), treatment-by-week interaction as fixed effects, baseline and baseline score-by-week interaction as covariates, with an unstructured working covariance matrix as default.
[35] - 1-sided p-values were obtained using MMRM Model. It was based on the one-sided alternative hypothesis testing that the treatment difference (TAK-906 - Placebo) in ANMS GCSI-DD recorded vomiting frequency was <0.

ANMS GCSI-DD Recorded Vomiting Frequency

Comparison groups

Placebo v TAK-906 Maleate 50 mg

Number of subjects included in analysis

107

Analysis specification

Pre-specified

Analysis type

superiority ^[36]

P-value

= 0.591 ^[37]

Method

MMRM

Parameter type

Least-Squares Mean Difference

Point estimate

0.08

Confidence interval

level

90%

sides

2-sided

lower limit

-0.47

upper limit

0.62

Variability estimate

Standard error of the mean

Dispersion value

0.33

Notes
[36] - MMRM model included week, treatment, participant disease population (DG/IG), treatment-by-week interaction as fixed effects, baseline and baseline score-by-week interaction as covariates, with an unstructured working covariance matrix as default.
[37] - 1-sided p-values were obtained using MMRM Model. It was based on the one-sided alternative hypothesis testing that the treatment difference (TAK-906 - Placebo) in ANMS GCSI-DD recorded vomiting frequency was <0.

Secondary: Change from Baseline in the ANMS GCSI-DD Overall Severity of Gastroparesis Symptoms Score at Week 12 of the Treatment Period

Top of page

End point title

Change from Baseline in the ANMS GCSI-DD Overall Severity of Gastroparesis Symptoms Score at Week 12 of the Treatment Period

End point description

ANMS GCSI-DD is a patient-reported outcome instrument for a symptom-based clinical trial endpoint in gastroparesis. The maximum total symptom score was (6 symptoms × maximum score 4 divided by 6) = 24/6 = 4. The ANMS GCSI-DD overall severity of gastroparesis symptoms 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. 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. Number analysed is the number of participants with data available for analysis.

End point type

Secondary

End point timeframe

Baseline and Week 12

End point values	Placebo	TAK-906 Maleate 5 mg	TAK-906 Maleate 25 mg	TAK-906 Maleate 50 mg
Number of subjects analysed	50	15	55	58
Units: score on a scale
least squares mean (standard error)	-1.20 ± 0.130	-1.02 ± 0.237	-1.22 ± 0.129	-1.25 ± 0.125

ANMS GCSI-DD Overall Severity of Gastroparesis

Comparison groups

Placebo v TAK-906 Maleate 5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[38]

P-value

= 0.742 ^[39]

Method

MMRM

Parameter type

Least-Squares Mean Difference

Point estimate

0.18

Confidence interval

level

90%

sides

2-sided

lower limit

-0.27

upper limit

0.62

Variability estimate

Standard error of the mean

Dispersion value

0.27

Notes
[38] - MMRM model included week, treatment, participant disease population (DG/IG), treatment-by-week interaction as fixed effects, baseline and baseline score-by-week interaction as covariates, with an unstructured working covariance matrix as default.
[39] - 1-sided p-values were obtained using MMRM Model. It was based on the one-sided alternative hypothesis testing that the treatment difference (TAK-906 - Placebo) in ANMS GCSI-DD overall severity of gastroparesis symptoms score was <0.

ANMS GCSI-DD Overall Severity of Gastroparesis

Comparison groups

Placebo v TAK-906 Maleate 25 mg

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

superiority ^[40]

P-value

= 0.461 ^[41]

Method

MMRM

Parameter type

Least-Squares Mean Difference

Point estimate

-0.02

Confidence interval

level

90%

sides

2-sided

lower limit

-0.32

upper limit

0.28

Variability estimate

Standard error of the mean

Dispersion value

0.183

Notes
[40] - MMRM model included week, treatment, participant disease population (DG/IG), treatment-by-week interaction as fixed effects, baseline and baseline score-by-week interaction as covariates, with an unstructured working covariance matrix as default.
[41] - 1-sided p-values were obtained using MMRM Model. It was based on the one-sided alternative hypothesis testing that the treatment difference (TAK-906 - Placebo) in ANMS GCSI-DD overall severity of gastroparesis symptoms score was <0.

ANMS GCSI-DD Overall Severity of Gastroparesis

Comparison groups

Placebo v TAK-906 Maleate 50 mg

Number of subjects included in analysis

108

Analysis specification

Pre-specified

Analysis type

superiority ^[42]

P-value

= 0.376 ^[43]

Method

MMRM

Parameter type

Least-Squares Mean Difference

Point estimate

-0.06

Confidence interval

level

90%

sides

2-sided

lower limit

-0.36

upper limit

0.24

Variability estimate

Standard error of the mean

Dispersion value

0.181

Notes
[42] - MMRM model included week, treatment, participant disease population (DG/IG), treatment-by-week interaction as fixed effects, baseline and baseline score-by-week interaction as covariates, with an unstructured working covariance matrix as default.
[43] - 1-sided p-values were obtained using MMRM Model. It was based on the one-sided alternative hypothesis testing that the treatment difference (TAK-906 - Placebo) in ANMS GCSI-DD overall severity of gastroparesis symptoms score was <0.

Secondary: Change from Baseline in the Bloating Severity Scale Score at Week 12 of the Treatment Period

Top of page

End point title

Change from Baseline in the Bloating Severity Scale Score at Week 12 of the Treatment Period

End point description

ANMS GCSI-DD is a patient-reported outcome instrument for a symptom-based clinical trial endpoint in gastroparesis. The bloating severity scale was scored from 0 to 4 (where 0 = no symptom and 4 = severe symptom). The maximum total symptom score could be (6 symptoms × maximum score 4 divided by 6)= 24/6 = 4. The ANMS GCSI-DD 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 analyses. 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. Number analysed is the number of participants with data available for analysis.

End point type

Secondary

End point timeframe

Baseline and Week 12

End point values	Placebo	TAK-906 Maleate 5 mg	TAK-906 Maleate 25 mg	TAK-906 Maleate 50 mg
Number of subjects analysed	50	15	55	58
Units: score on a scale
least squares mean (standard error)	-1.15 ± 0.137	-1.09 ± 0.250	-1.26 ± 0.136	-1.16 ± 0.132

Bloating Severity Scale Score

Comparison groups

Placebo v TAK-906 Maleate 5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[44]

P-value

= 0.591 ^[45]

Method

MMRM

Parameter type

Least-Squares Mean Difference

Point estimate

0.07

Confidence interval

level

90%

sides

2-sided

lower limit

-0.41

upper limit

0.54

Variability estimate

Standard error of the mean

Dispersion value

0.286

Notes
[44] - MMRM model included week, treatment, participant disease population (DG/IG), treatment-by-week interaction as fixed effects, baseline and baseline score-by-week interaction as covariates, with an unstructured working covariance matrix as default.
[45] - 1-sided p-values were obtained using MMRM Model. It was based on the one-sided alternative hypothesis testing that the treatment difference (TAK-906 - Placebo) in ANMS GCSI-DD bloating severity scale score was <0.

Bloating Severity Scale Score

Comparison groups

Placebo v TAK-906 Maleate 50 mg

Number of subjects included in analysis

108

Analysis specification

Pre-specified

Analysis type

superiority ^[46]

P-value

= 0.476 ^[47]

Method

MMRM

Parameter type

Least-Squares Mean Difference

Point estimate

-0.01

Confidence interval

level

90%

sides

2-sided

lower limit

-0.33

upper limit

0.3

Variability estimate

Standard error of the mean

Dispersion value

0.191

Notes
[46] - MMRM model included week, treatment, participant disease population (DG/IG), treatment-by-week interaction as fixed effects, baseline and baseline score-by-week interaction as covariates, with an unstructured working covariance matrix as default.
[47] - 1-sided p-values were obtained using MMRM Model. It was based on the one-sided alternative hypothesis testing that the treatment difference (TAK-906 - Placebo) in ANMS GCSI-DD bloating severity scale score was <0.

Bloating Severity Scale Score

Comparison groups

Placebo v TAK-906 Maleate 25 mg

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

superiority ^[48]

P-value

= 0.291 ^[49]

Method

MMRM

Parameter type

Least-Squares mean Difference

Point estimate

-0.11

Confidence interval

level

90%

sides

2-sided

lower limit

-0.43

upper limit

0.21

Variability estimate

Standard error of the mean

Dispersion value

0.193

Notes
[48] - MMRM model included week, treatment, participant disease population (DG/IG), treatment-by-week interaction as fixed effects, baseline and baseline score-by-week interaction as covariates, with an unstructured working covariance matrix as default.
[49] - 1-sided p-values were obtained using MMRM Model. It was based on the one-sided alternative hypothesis testing that the treatment difference (TAK-906 - Placebo) in ANMS GCSI-DD bloating severity scale score was <0.

Secondary: Change from Baseline in the ANMS GCSI-DD Total Score at Week 12 of the Treatment Period

Top of page

End point title

Change from Baseline in the ANMS GCSI-DD Total Score at Week 12 of the Treatment Period

End point description

ANMS GCSI-DD is a patient-reported outcome instrument for a symptom-based clinical trial endpoint in gastroparesis. The daily total score is calculated by summing the 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. The maximum total symptom score could be (6 symptoms × maximum score 4 divided by 6) = 24/6 = 4. The ANMS GCSI-DD 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 analyses. 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. Number analysed is the number of participants with data available for analysis.

End point type

Secondary

End point timeframe

Baseline and Week 12

End point values	Placebo	TAK-906 Maleate 5 mg	TAK-906 Maleate 25 mg	TAK-906 Maleate 50 mg
Number of subjects analysed	50	15	55	58
Units: score on a scale
least squares mean (standard error)	-1.10 ± 0.108	-1.00 ± 0.196	-1.09 ± 0.107	-1.11 ± 0.104

ANMS GCSI-DD Total Score

Comparison groups

Placebo v TAK-906 Maleate 5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[50]

P-value

= 0.675 ^[51]

Method

MMRM

Parameter type

Least-Squares Mean Difference

Point estimate

0.1

Confidence interval

level

90%

sides

2-sided

lower limit

-0.27

upper limit

0.47

Variability estimate

Standard error of the mean

Dispersion value

0.224

Notes
[50] - MMRM model included week, treatment, participant disease population (DG/IG), treatment-by-week interaction as fixed effects, baseline and baseline score-by-week interaction as covariates, with an unstructured working covariance matrix as default.
[51] - 1-sided p-values were obtained using MMRM Model. It was based on the one-sided alternative hypothesis testing that the treatment difference (TAK-906 - Placebo) in ANMS GCSI-DD total score was <0.

ANMS GCSI-DD Total Score

Comparison groups

Placebo v TAK-906 Maleate 25 mg

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

superiority ^[52]

P-value

= 0.531 ^[53]

Method

MMRM

Parameter type

Least-Squares Mean Difference

Point estimate

0.01

Confidence interval

level

90%

sides

2-sided

lower limit

-0.24

upper limit

0.26

Variability estimate

Standard error of the mean

Dispersion value

0.152

Notes
[52] - MMRM model included week, treatment, participant disease population (DG/IG), treatment-by-week interaction as fixed effects, baseline and baseline score-by-week interaction as covariates, with an unstructured working covariance matrix as default.
[53] - 1-sided p-values were obtained using MMRM Model. It was based on the one-sided alternative hypothesis testing that the treatment difference (TAK-906 - Placebo) in ANMS GCSI-DD total score was <0.

ANMS GCSI-DD Total Score

Comparison groups

Placebo v TAK-906 Maleate 50 mg

Number of subjects included in analysis

108

Analysis specification

Pre-specified

Analysis type

superiority ^[54]

P-value

= 0.473 ^[55]

Method

MMRM

Parameter type

Least-Squares Mean Difference

Point estimate

-0.01

Confidence interval

level

90%

sides

2-sided

lower limit

-0.26

upper limit

0.24

Variability estimate

Standard error of the mean

Dispersion value

0.15

Notes
[54] - MMRM model included week, treatment, participant disease population (DG/IG), treatment-by-week interaction as fixed effects, baseline and baseline score-by-week interaction as covariates, with an unstructured working covariance matrix as default.
[55] - 1-sided p-values were obtained using MMRM Model. It was based on the one-sided alternative hypothesis testing that the treatment difference (TAK-906 - Placebo) in ANMS GCSI-DD total score was <0.

Secondary: Percentage of Symptomatic Weeks

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End point title

Percentage of Symptomatic Weeks

End point description

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. 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.

End point type

Secondary

End point timeframe

Up to 12 weeks

End point values	Placebo	TAK-906 Maleate 5 mg	TAK-906 Maleate 25 mg	TAK-906 Maleate 50 mg
Number of subjects analysed	73	23	72	74
Units: percentage of weeks
least squares mean (standard error)	54.89 ± 4.746	46.42 ± 8.474	50.03 ± 4.781	51.31 ± 4.714

Statistical Analysis: Symptomatic Weeks

Comparison groups

Placebo v TAK-906 Maleate 5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.192 ^[56]

Method

ANOVA

Parameter type

Least-Squares Mean Difference

Point estimate

-8.47

Confidence interval

level

90%

sides

2-sided

lower limit

-24.5

upper limit

7.57

Variability estimate

Standard error of the mean

Dispersion value

9.71

Notes
[56] - The 1-sided p-value was based on the one-sided alternative hypothesis testing that the treatment difference (TAK-906 -Placebo) in symptomatic weeks was <0.

Statistical Analysis: Symptomatic Weeks

Comparison groups

Placebo v TAK-906 Maleate 25 mg

Number of subjects included in analysis

145

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.236 ^[57]

Method

ANOVA

Parameter type

Least-Squares Mean Difference

Point estimate

-4.85

Confidence interval

level

90%

sides

2-sided

lower limit

-15.98

upper limit

6.27

Variability estimate

Standard error of the mean

Dispersion value

6.736

Notes
[57] - The 1-sided p-value was based on the one-sided alternative hypothesis testing that the treatment difference (TAK-906 - Placebo) in symptomatic weeks was <0.

Statistical Analysis: Symptomatic Weeks

Comparison groups

Placebo v TAK-906 Maleate 50 mg

Number of subjects included in analysis

147

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.297 ^[58]

Method

ANOVA

Parameter type

Least-Squares Mean Difference

Point estimate

-3.58

Confidence interval

level

90%

sides

2-sided

lower limit

-14.62

upper limit

7.47

Variability estimate

Standard error of the mean

Dispersion value

6.689

Notes
[58] - The 1-sided p-value was based on the one-sided alternative hypothesis testing that the treatment difference (TAK-906 - Placebo) in symptomatic weeks was <0.

Secondary: 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

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End point title

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

End point description

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. 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. Number analyzed is the number of participants with data available for analysis.

End point type

Secondary

End point timeframe

Baseline and Week 12

End point values	Placebo	TAK-906 Maleate 5 mg	TAK-906 Maleate 25 mg	TAK-906 Maleate 50 mg
Number of subjects analysed	57	16	54	60
Units: score on a scale
least squares mean (standard error)	-1.33 ± 0.141	-1.25 ± 0.265	-1.51 ± 0.142	-1.57 ± 0.136

Statistical Analysis: PAGI-SYM Total Score

Comparison groups

Placebo v TAK-906 Maleate 5 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[59]

P-value

= 0.601 ^[60]

Method

MMRM

Parameter type

Least-Squares Mean Difference

Point estimate

0.08

Confidence interval

level

90%

sides

2-sided

lower limit

-0.42

upper limit

0.57

Variability estimate

Standard error of the mean

Dispersion value

0.3

Notes
[59] - MMRM model included week, treatment, participant disease population (DG/IG), treatment-by-week interaction as fixed effects, baseline and baseline score-by-week interaction as covariates, with an unstructured working covariance matrix as default.
[60] - 1-sided p-values were obtained using MMRM of PAGI-SYM total score. It was based on the one-sided alternative hypothesis testing that the treatment difference (TAK-906 - Placebo) in PAGI-SYM total score was <0.

Statistical Analysis: PAGI-SYM Total Score

Comparison groups

Placebo v TAK-906 Maleate 50 mg

Number of subjects included in analysis

117

Analysis specification

Pre-specified

Analysis type

superiority ^[61]

P-value

= 0.114 ^[62]

Method

MMRM

Parameter type

Least-Squares Mean Difference

Point estimate

-0.24

Confidence interval

level

90%

sides

2-sided

lower limit

-0.56

upper limit

0.09

Variability estimate

Standard error of the mean

Dispersion value

0.196

Notes
[61] - MMRM model included week, treatment, participant disease population (DG/IG), treatment-by-week interaction as fixed effects, baseline and baseline score-by-week interaction as covariates, with an unstructured working covariance matrix as default.
[62] - 1-sided p-values were obtained using MMRM of PAGI-SYM total score. It was based on the one-sided alternative hypothesis testing that the treatment difference (TAK-906 - Placebo) in PAGI-SYM total score was <0.

Statistical Analysis: PAGI-SYM Total Score

Comparison groups

Placebo v TAK-906 Maleate 25 mg

Number of subjects included in analysis

111

Analysis specification

Pre-specified

Analysis type

superiority ^[63]

P-value

= 0.181 ^[64]

Method

MMRM

Parameter type

Least-Squares Mean Difference

Point estimate

-0.18

Confidence interval

level

90%

sides

2-sided

lower limit

-0.51

upper limit

0.15

Variability estimate

Standard error of the mean

Dispersion value

0.2

Notes
[63] - MMRM model included week, treatment, participant disease population (DG/IG), treatment-by-week interaction as fixed effects, baseline and baseline score-by-week interaction as covariates, with an unstructured working covariance matrix as default.
[64] - 1-sided p-values were obtained using MMRM of PAGI-SYM total score. It was based on the one-sided alternative hypothesis testing that the treatment difference (TAK-906 - Placebo) in PAGI-SYM total score was <0.

Adverse events

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Timeframe for reporting adverse events

From the study start up to 30 days after end of treatment (up to approximately 16 weeks)

Adverse event reporting additional 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. Safety data was collected for all participants evaluable for response.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

Reporting group title

Placebo

Reporting group description

TAK-906 maleate placebo-matching capsules, orally, BID for up to 12 weeks.

Reporting group title

TAK-906 25 mg

Reporting group description

TAK-906 maleate 25 mg, capsules, orally, BID for up to 12 weeks.

Reporting group title

TAK-906 5 mg

Reporting group description

TAK-906 maleate 5 mg, capsules, orally, BID for up to 12 weeks.

Reporting group title

TAK-906 50 mg

Reporting group description

TAK-906 maleate 50 mg, capsules, orally, BID for up to 12 weeks.

Serious adverse events	Placebo	TAK-906 25 mg	TAK-906 5 mg	TAK-906 50 mg
Total subjects affected by serious adverse events
subjects affected / exposed	2 / 73 (2.74%)	2 / 72 (2.78%)	0 / 23 (0.00%)	2 / 74 (2.70%)
number of deaths (all causes)	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Oesophageal carcinoma
subjects affected / exposed	1 / 73 (1.37%)	0 / 72 (0.00%)	0 / 23 (0.00%)	0 / 74 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Intermittent claudication
subjects affected / exposed	0 / 73 (0.00%)	0 / 72 (0.00%)	0 / 23 (0.00%)	1 / 74 (1.35%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Diabetic foot
subjects affected / exposed	1 / 73 (1.37%)	0 / 72 (0.00%)	0 / 23 (0.00%)	0 / 74 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
COVID-19 pneumonia
subjects affected / exposed	0 / 73 (0.00%)	1 / 72 (1.39%)	0 / 23 (0.00%)	0 / 74 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Diabetic ketoacidosis
subjects affected / exposed	0 / 73 (0.00%)	0 / 72 (0.00%)	0 / 23 (0.00%)	1 / 74 (1.35%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypoglycaemia
subjects affected / exposed	0 / 73 (0.00%)	1 / 72 (1.39%)	0 / 23 (0.00%)	0 / 74 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Placebo	TAK-906 25 mg	TAK-906 5 mg	TAK-906 50 mg
Total subjects affected by non serious adverse events
subjects affected / exposed	0 / 73 (0.00%)	4 / 72 (5.56%)	2 / 23 (8.70%)	4 / 74 (5.41%)
Nervous system disorders
Headache
subjects affected / exposed	0 / 73 (0.00%)	4 / 72 (5.56%)	0 / 23 (0.00%)	0 / 74 (0.00%)
occurrences all number	0	4	0	0
Gastrointestinal disorders
Nausea
subjects affected / exposed	0 / 73 (0.00%)	0 / 72 (0.00%)	0 / 23 (0.00%)	4 / 74 (5.41%)
occurrences all number	0	0	0	4
Infections and infestations
Upper respiratory tract infection
subjects affected / exposed	0 / 73 (0.00%)	0 / 72 (0.00%)	2 / 23 (8.70%)	0 / 74 (0.00%)
occurrences all number	0	0	2	0

More information

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Were there any global substantial amendments to the protocol? Yes

16 Jul 2018

Amendment 1.0: The primary purpose of this amendment was to make following changes: • Updated the biomarkers to be analyzed and rationales. • Clarified the objective and endpoint for the gastric emptying breath test (GEBT) and the timing of GEBT relative to dosing of study drug. • Clarified the criteria for use of rescue medication for nausea and vomiting. • Updated the participant eligibility criteria. • Updated the list of excluded medications. • Updated the safety section with guidance to investigators for management of extrapyramidal symptoms (EPS) and central nervous system (CNS)/neuropsychiatric AEs. • Clarified the primary efficacy analysis.

06 Aug 2018

Amendment 2.0: The primary purpose of this amendment was to make following changes: • Updated the secondary endpoints. • Updated the biomarkers to be analysed.

08 Aug 2019

Amendment 6.0: The primary purpose of this amendment was to make following changes: • Added text about the effects of estimated glomerular filtration rate (eGFR) on exposure of TAK-906 and the effects of the co-administration of esomeprazole on area under the concentration-time curve from time 0 to infinity (AUC∞) and maximum observed concentration (Cmax) of TAK-906. • Deleted the requirement for medication to be taken on an empty stomach (at least 2 hours of fasting except for water). • Revised the interim analysis by adding a futility analysis. • Clarified the use of rescue medication. • Revised exclusion criterion #26 to define prolonged corrected QT interval (QTcF) as ≥450 milliseconds and to exclude participants with risk factors for QT interval prolongation. • Revised exclusion criterion #31 to exclude participants who have any signs and/or symptoms or history of extrapyramidal system disease or history of suicide attempt. • Changed exclusion criterion #37 to exclude participants with renal impairment, defined as a lower limit of eGFR <30 mL/min at screening visit and deleted the formulas for calculating eGFR in various participant populations. • Revised the list of excluded medications. • Removed the stipulation that participants who had taken <80% of study drug in the previous 4-week period would be withdrawn from the study because of noncompliance with study drug. • Added the criteria that participants who were <80% compliant or who missed ≥6 consecutive doses since the last study visit would be re-educated about the importance of being consistent with their dosing per the protocol.

13 Jul 2020

Amendment 8.0: The primary purpose of this amendment was to make following changes: • Updated the period of evaluation from 17 to 22 weeks from screening to follow-up. • Removed GEBT at Visits 5 and 7; GEBT may still have been performed at Visit 2 if it was required for diagnostic confirmation of delayed gastric emptying. • Removed exploratory biomarker sample collection. • Discontinued randomization into the 5 mg dose arm. • Reduced the planned sample size by 10 participants per arm to 60 participants per treatment groups of placebo, TAK-906M 25 mg, and TAK-906M 50 mg. • Removed the minimum number of DG and IG participants in each dose arm. • Revised the statistical testing from 2-sided (with a significance level of 5%) to 1-sided (with a significance level of 5%). • Shortened the safety follow-up phone call from 40 to 30 days. • Added exclusion criterion #41 for any participant with suspected or known COVID-19 infection and addressed possible changes to study procedures necessitated by the COVID-19 pandemic. • Added OATP1B1/1B3 inhibitors and otilonium bromide (Spasmomen) to excluded medications. • Removed the planned interim efficacy analysis. • Updated the patient global impression of severity (PGI-S) scale; replaced the patient global impression of improvement (PGI-I) scale with the patient global impression of change (PGI-C) scale.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: 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

Primary: 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

Secondary: Percentage of Participants with at Least 50% Reduction from Baseline in ANMS GCSI-DD Composite Score at Week 12

Secondary: Percentage of Participants with at Least 50% Reduction from Baseline in ANMS GCSI-DD Composite Score at Week 12

Secondary: Change from Baseline in the ANMS GCSI-DD Nausea Symptom Score at Week 12 of the Treatment Period

Secondary: Change from Baseline in the ANMS GCSI-DD Nausea Symptom Score at Week 12 of the Treatment Period

Secondary: Change from Baseline in the ANMS GCSI-DD Early Satiety Symptom Score at Week 12 of the Treatment Period

Secondary: Change from Baseline in the ANMS GCSI-DD Early Satiety Symptom Score at Week 12 of the Treatment Period

Secondary: Change from Baseline in the ANMS GCSI-DD Postprandial Fullness Symptom Score at Week 12 of the Treatment Period

Secondary: Change from Baseline in the ANMS GCSI-DD Postprandial Fullness Symptom Score at Week 12 of the Treatment Period

Secondary: Change from Baseline in the ANMS GCSI-DD Upper Abdominal Pain Symptom Score at Week 12 of the Treatment Period

Secondary: Change from Baseline in the ANMS GCSI-DD Upper Abdominal Pain Symptom Score at Week 12 of the Treatment Period

Secondary: Change from Baseline in the ANMS GCSI-DD Recorded Vomiting Frequency at Week 12 of the Treatment Period

Secondary: Change from Baseline in the ANMS GCSI-DD Recorded Vomiting Frequency at Week 12 of the Treatment Period

Secondary: Change from Baseline in the ANMS GCSI-DD Overall Severity of Gastroparesis Symptoms Score at Week 12 of the Treatment Period

Secondary: Change from Baseline in the ANMS GCSI-DD Overall Severity of Gastroparesis Symptoms Score at Week 12 of the Treatment Period

Secondary: Change from Baseline in the Bloating Severity Scale Score at Week 12 of the Treatment Period

Secondary: Change from Baseline in the Bloating Severity Scale Score at Week 12 of the Treatment Period

Secondary: Change from Baseline in the ANMS GCSI-DD Total Score at Week 12 of the Treatment Period

Secondary: Change from Baseline in the ANMS GCSI-DD Total Score at Week 12 of the Treatment Period

Secondary: Percentage of Symptomatic Weeks

Secondary: Percentage of Symptomatic Weeks

Secondary: 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

Secondary: 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

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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France
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Portugal
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Slovenia
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Outside EU/EEA