Diabetic Gastroparesis, Idiopathic Gastroparesis
Conditions
Brief summary
The purpose of this study is to assess the safety and efficacy of various dose levels of NG101 compared with placebo in adult participants with gastroparesis during 12 weeks of treatment.
Detailed description
This is a randomized, double-blind, parallel-group , placebo-controlled, multicenter US-based study to evaluate the safety and efficacy of 3 dose levels of NG101 (Metopimazine mesylate) compared with placebo in participants with diabetic or idiopathic gastroparesis. The study will enroll approximately 140 participants. Following the Screening Period, there is a 2-week Pretreatment Period during which participants will complete an electronic daily diary. Participants eligible for the clinical study will be randomly assigned (in a 1:1:1:1 ratio) to receive either NG101 5 mg, 10 mg, or 20 mg, or matching placebo during a 12-week Treatment Period. All participants will be asked to take one capsule 30 minutes before a meal 3 times a day and 30 minutes before bedtime for a total of 4 capsules daily (QID). The total duration of the study for each participant will be approximately 20 weeks.
Interventions
DRUGNG101
Capsules
DRUGPlacebo
Capsules
Sponsors
Neurogastrx, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Parallel Assignment
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult patients with diabetic or idiopathic gastroparesis * Symptoms consistent with gastroparesis (nausea, vomiting, early satiety, post-prandial fullness, and abdominal pain) * Documented evidence of no mechanical obstruction * Delayed gastric emptying as demonstrated by gastric scintigraphy or breath test
Exclusion criteria
* Uncontrolled diabetes (defined as HgbA1c \> 10%) * Severe postural symptoms or evidence of unexplained recurrent dizziness * Participant has received and tolerated domperidone and showed no notable symptomatic improvement in gastroparesis symptoms * Participant has had endoscopic pyloric injections of botulinum toxin within the 6 months prior to the Screening Visit. * Participant engages in daily recreational use of marijuana * Prolactin levels \> 2 x ULN
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline of Nausea Severity Score | Baseline to Week 12 | Change from Baseline at Weeks 7 through 12 (average) as measured by the Diabetic and Idiopathic Gastroparesis Symptoms Daily Diary (DIGS-DD). Participants were asked to rate their symptoms at their worst in the past 24 hours using a 0 to 10-point numeric rating scale (NRS). A score of 0 indicates no symptoms and a score of 10 indicates the worst possible symptoms. For each week in the 2-week Pretreatment Period, the 12-week Treatment Period, and the 2-week Follow-up Period, a participant's score for that week was the mean of the daily scores for that week. A negative change from baseline indicates improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Early Satiety Severity Score | Baseline to Week 12 | Change from baseline at Weeks 7 through 12 (average) as measured by the Diabetic and Idiopathic Gastroparesis Symptoms Daily Diary (DIGS-DD) for early satiety severity score. Participants were asked to rate their symptoms at their worst in the past 24 hours using a 0 to 10-point numeric rating scale (NRS). A score of 0 indicates no symptoms and a score of 10 indicates the worst possible symptoms. For each week in the 2-week Pretreatment Period, the 12-week Treatment Period, and the 2-week Follow-up Period, a participant's score for that week was the mean of the daily scores for that week. A negative change from baseline indicates improvement. |
| Change From Baseline in Postprandial Fullness Severity Score | Baseline to Week 12 | Change from baseline at Weeks 7 through 12 (average) as measured by patient's daily diary entries during participation in the study for postprandial fullness severity score. Participants were asked to rate their symptoms at their worst in the past 24 hours using a 0 to 10-point numeric rating scale (NRS). A score of 0 indicates no symptoms and a score of 10 indicates the worst possible symptoms. For each week in the 2-week Pretreatment Period, the 12-week Treatment Period, and the 2-week Follow-up Period. A negative change from baseline indicates improvement. |
| Change From Baseline in Abdominal Pain Severity Score | Baseline to Week 12 | Change from baseline at Weeks 7 through 12 (average) as measured by patient's daily diary entries during participation in the study for postprandial fullness severity score. Participants were asked to rate their symptoms at their worst in the past 24 hours using a 0 to 10-point numeric rating scale (NRS). A score of 0 indicates no symptoms and a score of 10 indicates the worst possible symptoms. For each week in the 2-week Pretreatment Period, the 12-week Treatment Period, and the 2-week Follow-up Period. A negative change from baseline indicates improvement. |
| Change From Baseline in Discrete Episodes of Vomiting | Baseline to Week 12 | Change from baseline at Weeks 7 through 12 (average) as measured by patient's daily diary entries during participation in the study for the number of discrete episodes of vomiting. Participants were asked to record the number of episodes of vomiting in the past 24 hours. Each episode counts as 1. A negative change from baseline indicates improvement. |
| Change From Baseline in 3-symptom Severity Score | Baseline to Week 12 | Change from baseline at Weeks 7 through 12 (average) as measured by patient's daily diary entries during participation in the study for 3-symptom severity score. Participants were asked to rate their symptoms at their worst in the past 24 hours using a 0 to 10-point numeric rating scale (NRS). A score of 0 indicates no symptoms and a score of 10 indicates the worst possible symptoms. For each week, the 3-symptom severity score is the average of the mean daily scores of nausea, early satiety, and postprandial fullness severity scores. A negative change from baseline indicates improvement. |
| Change From Baseline in 4-symptom Severity Score | Baseline to Week 12 | Change from baseline at Weeks 7 through 12 (average) as measured by patient's daily diary entries during participation in the study for 4-symptom severity score. Participants were asked to rate their symptoms at their worst in the past 24 hours using a 0 to 10-point numeric rating scale (NRS). A score of 0 indicates no symptoms and a score of 10 indicates the worst possible symptoms. For each week, the 4-symptom severity score is the average of the mean daily scores of nausea, early satiety, postprandial fullness, and abdominal pain severity scores. A negative change from baseline indicates improvement |
Countries
United States
Participant flow
Recruitment details
Participants with symptomatic idiopathic or diabetic gastroparesis took part in the study at 51 investigative sites in the United States from 01 August 2020 to 25 February 2023
Pre-assignment details
Participants eligible for the study were randomized in a 1:1:1:1 ratio to receive either NG101 treatment arms of 5 mg, 10 mg, or 20 mg, or matching placebo during a 12-week Treatment Period. Randomization was stratified on the following factors: gastroparesis etiology (diabetes vs idiopathic), sex (male vs female), and current cannabinoid use (yes vs no).
Participants by arm
| Arm | Count |
|---|---|
| NG101 - 5 mg NG101 5 mg, capsules, orally, QID (4 times a day) for up to 12 weeks
NG101: Capsules | 40 |
| NG101 - 10 mg NG101 10 mg, capsules, orally, QID (4 times a day) for up to 12 weeks
NG101: Capsules | 41 |
| NG101 - 20 mg NG101 20 mg, capsules, orally, QID (4 times a day) for up to 12 weeks
NG101: Capsules | 40 |
| Placebo Placebo-matching, capsules, orally, QID (4 times a day) for up to 12 weeks
Placebo: Capsules | 40 |
| Total | 161 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 3 | 7 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 | 1 | 4 |
| Overall Study | No study drug administered or protocol deviation | 0 | 2 | 0 | 2 |
| Overall Study | Withdrawal by Subject | 3 | 1 | 1 | 1 |
Baseline characteristics
| Characteristic | NG101 - 5 mg | NG101 - 10 mg | NG101 - 20 mg | Placebo | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 8 Participants | 9 Participants | 10 Participants | 11 Participants | 38 Participants |
| Age, Categorical Between 18 and 65 years | 32 Participants | 32 Participants | 30 Participants | 29 Participants | 123 Participants |
| Age, Continuous | 52.7 years STANDARD_DEVIATION 11.5 | 53.7 years STANDARD_DEVIATION 11.26 | 55.7 years STANDARD_DEVIATION 13.5 | 55.4 years STANDARD_DEVIATION 14.19 | 54.5 years STANDARD_DEVIATION 12.62 |
| Cannabinoid use No | 36 Participants | 38 Participants | 37 Participants | 35 Participants | 146 Participants |
| Cannabinoid use Yes | 4 Participants | 3 Participants | 3 Participants | 5 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 17 Participants | 20 Participants | 20 Participants | 16 Participants | 73 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 23 Participants | 21 Participants | 20 Participants | 24 Participants | 88 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Gastroparesis etiology Diabetic | 18 Participants | 19 Participants | 19 Participants | 17 Participants | 73 Participants |
| Gastroparesis etiology Idiopathic | 22 Participants | 22 Participants | 21 Participants | 23 Participants | 88 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 9 Participants | 4 Participants | 9 Participants | 23 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 39 Participants | 32 Participants | 33 Participants | 30 Participants | 134 Participants |
| Region of Enrollment United States | 40 participants | 41 participants | 40 participants | 40 participants | 161 participants |
| Sex: Female, Male Female | 33 Participants | 34 Participants | 33 Participants | 33 Participants | 133 Participants |
| Sex: Female, Male Male | 7 Participants | 7 Participants | 7 Participants | 7 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 40 | 0 / 41 | 0 / 40 | 0 / 40 |
| other Total, other adverse events | 15 / 40 | 12 / 41 | 21 / 40 | 14 / 40 |
| serious Total, serious adverse events | 1 / 40 | 0 / 41 | 1 / 40 | 0 / 40 |
Outcome results
Primary
Change From Baseline of Nausea Severity Score
Change from Baseline at Weeks 7 through 12 (average) as measured by the Diabetic and Idiopathic Gastroparesis Symptoms Daily Diary (DIGS-DD). Participants were asked to rate their symptoms at their worst in the past 24 hours using a 0 to 10-point numeric rating scale (NRS). A score of 0 indicates no symptoms and a score of 10 indicates the worst possible symptoms. For each week in the 2-week Pretreatment Period, the 12-week Treatment Period, and the 2-week Follow-up Period, a participant's score for that week was the mean of the daily scores for that week. A negative change from baseline indicates improvement.
Time frame: Baseline to Week 12
Population: Per Protocol population included all participants in the Intent-To-Treat Population (all enrolled participants who were randomized) who do not have any major protocol deviations that would affect efficacy as determined by the study team.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| NG101 - 5 mg | Change From Baseline of Nausea Severity Score | -3.55 units on a scale | Standard Error 0.331 |
| NG101 - 10 mg | Change From Baseline of Nausea Severity Score | -3.65 units on a scale | Standard Error 0.0348 |
| NG101 - 20 mg | Change From Baseline of Nausea Severity Score | -3.43 units on a scale | Standard Error 0.348 |
| Placebo | Change From Baseline of Nausea Severity Score | -2.83 units on a scale | Standard Error 0.347 |
p-value: 0.13595% CI: [-1.67, 0.23]ANOVA
p-value: 0.099795% CI: [-1.79, 0.16]ANCOVA
p-value: 0.219595% CI: [-1.58, 0.37]ANCOVA
Secondary
Change From Baseline in 3-symptom Severity Score
Change from baseline at Weeks 7 through 12 (average) as measured by patient's daily diary entries during participation in the study for 3-symptom severity score. Participants were asked to rate their symptoms at their worst in the past 24 hours using a 0 to 10-point numeric rating scale (NRS). A score of 0 indicates no symptoms and a score of 10 indicates the worst possible symptoms. For each week, the 3-symptom severity score is the average of the mean daily scores of nausea, early satiety, and postprandial fullness severity scores. A negative change from baseline indicates improvement.
Time frame: Baseline to Week 12
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| NG101 - 5 mg | Change From Baseline in 3-symptom Severity Score | -3.16 units on a scale | Standard Error 0.334 |
| NG101 - 10 mg | Change From Baseline in 3-symptom Severity Score | -3.28 units on a scale | Standard Error 0.351 |
| NG101 - 20 mg | Change From Baseline in 3-symptom Severity Score | -2.92 units on a scale | Standard Error 0.352 |
| Placebo | Change From Baseline in 3-symptom Severity Score | -2.85 units on a scale | Standard Error 0.352 |
p-value: 0.52595% CI: [-1.27, 0.65]ANCOVA
p-value: 0.399195% CI: [-1.41, 0.56]ANCOVA
p-value: 0.900695% CI: [-1.05, 0.92]ANCOVA
Secondary
Change From Baseline in 4-symptom Severity Score
Change from baseline at Weeks 7 through 12 (average) as measured by patient's daily diary entries during participation in the study for 4-symptom severity score. Participants were asked to rate their symptoms at their worst in the past 24 hours using a 0 to 10-point numeric rating scale (NRS). A score of 0 indicates no symptoms and a score of 10 indicates the worst possible symptoms. For each week, the 4-symptom severity score is the average of the mean daily scores of nausea, early satiety, postprandial fullness, and abdominal pain severity scores. A negative change from baseline indicates improvement
Time frame: Baseline to Week 12
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| NG101 - 5 mg | Change From Baseline in 4-symptom Severity Score | -3.04 units on a scale | Standard Error 0.306 |
| NG101 - 10 mg | Change From Baseline in 4-symptom Severity Score | -3.14 units on a scale | Standard Error 0.321 |
| NG101 - 20 mg | Change From Baseline in 4-symptom Severity Score | -2.74 units on a scale | Standard Error 0.322 |
| Placebo | Change From Baseline in 4-symptom Severity Score | -2.81 units on a scale | Standard Error 0.321 |
p-value: 0.600995% CI: [-1.11, 0.64]ANCOVA
p-value: 0.465495% CI: [-1.23, 0.56]ANCOVA
p-value: 0.884295% CI: [-0.83, 0.97]ANCOVA
Secondary
Change From Baseline in Abdominal Pain Severity Score
Change from baseline at Weeks 7 through 12 (average) as measured by patient's daily diary entries during participation in the study for postprandial fullness severity score. Participants were asked to rate their symptoms at their worst in the past 24 hours using a 0 to 10-point numeric rating scale (NRS). A score of 0 indicates no symptoms and a score of 10 indicates the worst possible symptoms. For each week in the 2-week Pretreatment Period, the 12-week Treatment Period, and the 2-week Follow-up Period. A negative change from baseline indicates improvement.
Time frame: Baseline to Week 12
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| NG101 - 5 mg | Change From Baseline in Abdominal Pain Severity Score | -2.65 units on a scale | Standard Error 0.28 |
| NG101 - 10 mg | Change From Baseline in Abdominal Pain Severity Score | -2.69 units on a scale | Standard Error 0.292 |
| NG101 - 20 mg | Change From Baseline in Abdominal Pain Severity Score | -2.19 units on a scale | Standard Error 0.293 |
| Placebo | Change From Baseline in Abdominal Pain Severity Score | -2.70 units on a scale | Standard Error 0.295 |
p-value: 0.903495% CI: [-0.76, 0.86]ANCOVA
p-value: 0.974295% CI: [-0.68, 0.63]ANCOVA
p-value: 0.223595% CI: [-0.31, 1.33]ANCOVA
Secondary
Change From Baseline in Discrete Episodes of Vomiting
Change from baseline at Weeks 7 through 12 (average) as measured by patient's daily diary entries during participation in the study for the number of discrete episodes of vomiting. Participants were asked to record the number of episodes of vomiting in the past 24 hours. Each episode counts as 1. A negative change from baseline indicates improvement.
Time frame: Baseline to Week 12
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| NG101 - 5 mg | Change From Baseline in Discrete Episodes of Vomiting | -0.42 units on a scale | Standard Error 0.081 |
| NG101 - 10 mg | Change From Baseline in Discrete Episodes of Vomiting | -0.50 units on a scale | Standard Error 0.085 |
| NG101 - 20 mg | Change From Baseline in Discrete Episodes of Vomiting | -0.40 units on a scale | Standard Error 0.085 |
| Placebo | Change From Baseline in Discrete Episodes of Vomiting | -0.31 units on a scale | Standard Error 0.085 |
p-value: 0.356795% CI: [-0.34, 0.12]ANCOVA
p-value: 0.112995% CI: [-0.43, 0.05]ANCOVA
p-value: 0.45995% CI: [-0.33, 0.15]ANCOVA
Secondary
Change From Baseline in Early Satiety Severity Score
Change from baseline at Weeks 7 through 12 (average) as measured by the Diabetic and Idiopathic Gastroparesis Symptoms Daily Diary (DIGS-DD) for early satiety severity score. Participants were asked to rate their symptoms at their worst in the past 24 hours using a 0 to 10-point numeric rating scale (NRS). A score of 0 indicates no symptoms and a score of 10 indicates the worst possible symptoms. For each week in the 2-week Pretreatment Period, the 12-week Treatment Period, and the 2-week Follow-up Period, a participant's score for that week was the mean of the daily scores for that week. A negative change from baseline indicates improvement.
Time frame: Baseline to Week 12
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| NG101 - 5 mg | Change From Baseline in Early Satiety Severity Score | -3.02 units on a scale | Standard Error 0.343 |
| NG101 - 10 mg | Change From Baseline in Early Satiety Severity Score | -3.23 units on a scale | Standard Error 0.36 |
| NG101 - 20 mg | Change From Baseline in Early Satiety Severity Score | -2.64 units on a scale | Standard Error 0.362 |
| Placebo | Change From Baseline in Early Satiety Severity Score | -2.89 units on a scale | Standard Error 0.361 |
p-value: 0.794495% CI: [-1.11, 0.85]ANCOVA
p-value: 0.495695% CI: [-1.36, 0.66]ANCOVA
p-value: 0.62695% CI: [-0.76, 1.26]ANCOVA
Secondary
Change From Baseline in Postprandial Fullness Severity Score
Change from baseline at Weeks 7 through 12 (average) as measured by patient's daily diary entries during participation in the study for postprandial fullness severity score. Participants were asked to rate their symptoms at their worst in the past 24 hours using a 0 to 10-point numeric rating scale (NRS). A score of 0 indicates no symptoms and a score of 10 indicates the worst possible symptoms. For each week in the 2-week Pretreatment Period, the 12-week Treatment Period, and the 2-week Follow-up Period. A negative change from baseline indicates improvement.
Time frame: Baseline to Week 12
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| NG101 - 5 mg | Change From Baseline in Postprandial Fullness Severity Score | -2.94 units on a scale | Standard Error 0.373 |
| NG101 - 10 mg | Change From Baseline in Postprandial Fullness Severity Score | -2.96 units on a scale | Standard Error 0.392 |
| NG101 - 20 mg | Change From Baseline in Postprandial Fullness Severity Score | -2.67 units on a scale | Standard Error 0.393 |
| Placebo | Change From Baseline in Postprandial Fullness Severity Score | -2.87 units on a scale | Standard Error 0.394 |
p-value: 0.886695% CI: [-1.15, 1]ANCOVA
p-value: 0.869995% CI: [-1.19, 1.01]ANCOVA
p-value: 0.729795% CI: [-0.91, 1.29]ANCOVA