Study to Assess the Efficacy of VLY-686 in Relieving Symptoms of Gastroparesis

The Gastroparesis Core Symptom Daily Diary (GCSDD) is a patient reported diary that asks patients to rate the worst occurrence of each cardinal symptom of gastroparesis (nausea severity, early satiety, postprandial fullness, bloating, and abdominal pain) in the past 24 hours on a Likert scale from 0 (no symptoms) to 5 (very severe). Change from baseline in average nausea severity score is calculated as the weekly average post value minus baseline value of the daily nausea severity score from the GCSDD. A negative change indicates improvement.

Time frame: 4 weeks

Population: The ITT Population included any subject randomized into the study who received a dose of study medication and had at least 1 valid postbaseline efficacy measurement while on study medication. The ITT Population comprised 141 subjects.

The Clinician Global Impression of Severity (CGI-S) is a 7-point scale on which the clinician rates the severity of the patient's gastroparesis at the time of the assessment and refers to the degree of illness at the time of the visit and during the 2 weeks before the visit. The CGI-S is rated on the following 7-point scale: 1: normal, not at all ill; 2: borderline ill: 3: mildly ill; 4: moderately ill; 5: markedly ill; 6: severely ill; 7: among the most extremely ill patients. Change from baseline is calculated as post value minus baseline value. A negative change indicates improvement.

Time frame: 4 weeks

The Gastroparesis Core Symptom Daily Diary (GCSDD) is a patient reported diary that asks patients if they have vomited in the past 24 hours and how many times they vomited in the past 24 hours. Change from baseline in the weekly average of daily vomiting frequency is calculated as the weekly average post value minus baseline value of the daily daily vomiting frequency from the GCSDD. Baseline is defined as the average of all non-missing values in the screening phase (4 weeks). A negative change indicates improvement.

Time frame: 4 weeks

The GCSI is a subject reported outcome administered in-clinic with a 2-week recall period to measure the severity of symptoms in gastroparesis. The GCSI is composed of 9 items based on three subscales: post-prandial fullness/early satiety (4 items); nausea/vomiting (3 items), and bloating (2 items). The severity of each symptom is rated on a six-point Likert response scale. The minimal scale value = 0 (none) and the maximum scale value = 5 (very severe). GCSI Total score is constructed as the average of the three symptom sub-scales. Higher score is indicative of greater symptom severity.

Time frame: 4 weeks

The PAGI-SYM is a patient reported outcome which asks patients to describe the severity of their symptoms over the last two weeks to measure symptom severity for gastroparesis, functional dyspepsia, and gastroesophageal reflux disease. The measure consists of 20 symptom severity items, which cover the following domains: nausea/vomiting, fullness/early satiety, bloating, upper abdominal pain, heartburn/regurgitation, and lower abdominal pain. This questionnaire includes the Gastroparesis Cardinal Symptom Index (GCSI). The severity of each symptom is rated on a six-point Likert response scale. The minimal scale value = 0 (none) and the maximum scale value= 5 (very severe). PAGI-SYM Total score is constructed as the average of the six symptom sub-scales and a higher score is indicative of greater symptom severity.

Time frame: 4 weeks

The Patient Global Impression of Change (PGI-C) is a patient reported questionnaire with a 7-point rating scale where the participant rates his/her own improvement in overall symptoms relative to the baseline assessment. Is is rated as 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse. Higher scores indicate a worse outcome.

Time frame: 4 weeks

The Gastroparesis Core Symptom Daily Diary (GCSDD) is a patient reported diary that asks patients if they have had any nausea over the past 24 hours and if yes, to rate the worst occurrence in the past 24 hours on a Likert scale from 1 (very mild) to 5 (very severe). Change in weekly percentage of nausea-free days from baseline is calculated as weekly average post value minus baseline value. Baseline is defined as the average of all nonmissing values in the screening phase (4 weeks).

Time frame: 4 weeks

The Clinician Global Impression of Severity (CGI-S) is a 7-point scale on which the clinician rates the severity of the patient's gastroparesis at the time of the assessment and refers to the degree of illness at the time of the visit and during the 2 weeks before the visit. The CGI-S is rates on the following 7-point scale: 1: normal, not at all ill; 2: borderline ill: 3: mildly ill; 4: moderately ill; 5: markedly ill; 6: severely ill; 7: among the most extremely ill patients. Change from baseline is calculated as post value minus baseline value. A negative change indicates improvement.

Time frame: 4 weeks

Population: The baseline vomiting group subpopulation was defined as all subjects who reported at least 1 episode of vomiting during the screening period and consisted of 101 of 141 (72%) patients of the ITT population.

The Gastroparesis Core Symptom Daily Diary (GCSDD) is a patient reported diary that asks patients to rate the worst occurrence of each cardinal symptom of gastroparesis (nausea severity, early satiety, postprandial fullness, bloating, and abdominal pain) in the past 24 hours on a Likert scale from 0 (no symptoms) to 5 (very severe). Change from baseline in average nausea severity score is calculated as the weekly average post value minus baseline value of the daily nausea severity score from the GCSDD. A negative change indicates improvement.

Time frame: 4 weeks

Population: The baseline vomiting group subpopulation was defined as all subjects who reported at least 1 episode of vomiting during the screening period and consisted of 101 of 141 (72%) patients of the ITT population.

Defined as a nausea score of 0 in at week 4. Nausea severity is rated on a Likert scale from 0 (none) to 5 (very severe).

Time frame: 4 weeks

Defined as a nausea score of 0 at week 4. Nausea severity is rated on a Likert scale from 0 (none) to 5 (very severe).

Time frame: 4 weeks

Population: The baseline vomiting group subpopulation was defined as all subjects who reported at least 1 episode of vomiting during the screening period and consisted of 101 of 141 (72%) patients of the ITT population.

The GCSI is a subject reported outcome administered in-clinic with a 2-week recall period to measure the severity of symptoms in gastroparesis. The GCSI is composed of 9 items based on three subscales: post-prandial fullness/early satiety (4 items); nausea/vomiting (3 items), and bloating (2 items). The severity of each symptom is rated on a six-point Likert response scale. The minimal scale value = 0 (none) and the maximum scale value = 5 (very severe). GCSI Total score is constructed as the average of the three symptom sub-scales. Higher score is indicative of greater symptom severity.

Time frame: 4 weeks

Population: The baseline vomiting group subpopulation was defined as all subjects who reported at least 1 episode of vomiting during the screening period and consisted of 101 of 141 (72%) patients of the ITT population.

The Gastroparesis Core Symptom Daily Diary (GCSDD) is a patient reported diary that asks patients to rate the worst occurrence of each cardinal symptom of gastroparesis in the past 24 hours on a scale from 0 (no symptoms) to 5 (very severe). Change from baseline is calculated as post value minus baseline value. A negative change indicates improvement.

Time frame: 4 weeks

Population: The baseline vomiting group subpopulation was defined as all subjects who reported at least 1 episode of vomiting during the screening period and consisted of 101 of 141 (72%) patients of the ITT population.

The Gastroparesis Core Symptom Daily Diary (GCSDD) is a patient reported diary that asks patients to rate the worst occurrence of each cardinal symptom of gastroparesis in the past 24 hours on a scale from 0 (no symptoms) to 5 (very severe).

Time frame: 4 weeks

Population: The baseline vomiting group subpopulation was defined as all subjects who reported at least 1 episode of vomiting during the screening period and consisted of 101 of 141 (72%) patients of the ITT population.

Defined as a nausea score of very mild or better (≤1) in average daily nausea severity at week 4. Nausea severity is rated on a Likert scale from 0 (none) to 5 (very severe).

Time frame: 4 weeks

Defined as a nausea score of very mild or better (≤1) in average daily nausea severity at week 4. Nausea severity is rated on a Likert scale from 0 (none) to 5 (very severe).

Time frame: 4 weeks

Population: The baseline vomiting group subpopulation was defined as all subjects who reported at least 1 episode of vomiting during the screening period and consisted of 101 of 141 (72%) patients of the ITT population.

The PAGI-SYM is a patient reported outcome which asks patients to describe the severity of their symptoms over the last two weeks to measure symptom severity for gastroparesis, functional dyspepsia, and gastroesophageal reflux disease. The measure consists of 20 symptom severity items, which cover the following domains: nausea/vomiting, fullness/early satiety, bloating, upper abdominal pain, heartburn/regurgitation, and lower abdominal pain. This questionnaire includes the Gastroparesis Cardinal Symptom Index (GCSI). The severity of each symptom is rated on a six-point Likert response scale. The minimal scale value = 0 (none) and the maximum scale value= 5 (very severe). PAGI-SYM Total score is constructed as the average of the six symptom sub-scales and a higher score is indicative of greater symptom severity.

Time frame: 4 weeks

Population: The baseline vomiting group subpopulation was defined as all subjects who reported at least 1 episode of vomiting during the screening period and consisted of 101 of 141 (72%) patients of the ITT population.

Defined as 1-point or greater improvement on their GCSI total score from baseline to week 4. The GCSI is a subject reported outcome. Part I consists of the traditional GCSI and severity rating of upper abdominal pain and severity of overall symptoms on a 0 (none) to 5 (very severe) Likert scale. Part II uses a 7-point rating scale for the subject to rate their own improvement relative to baseline. Symptoms are rated as: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse. The GCSI subscale scores, nausea/vomiting (3 items), postprandial fullness/early satiety (4 items), bloating (2 items), and upper abdominal pain (2 items), are calculated by taking the mean of non-missing items in each subscale; the subscale scores vary from 0 (none or absent) to 5 (very severe). The total score is calculated by taking the mean of the three subscales (except upper abdominal pain and overall symptom item).

Time frame: 4 weeks

Defined as 1-point or greater improvement on their GCSI total score from baseline to week 4. The GCSI is a subject reported outcome. Part I consists of the traditional GCSI and severity rating of upper abdominal pain and severity of overall symptoms on a 0 (none) to 5 (very severe) Likert scale. Part II uses a 7-point rating scale for the subject to rate their own improvement relative to baseline. Symptoms are rated as: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse. The GCSI subscale scores, nausea/vomiting (3 items), postprandial fullness/early satiety (4 items), bloating (2 items), and upper abdominal pain (2 items), are calculated by taking the mean of non-missing items in each subscale; the subscale scores vary from 0 (none or absent) to 5 (very severe). The total score is calculated by taking the mean of the three subscales (except upper abdominal pain and overall symptom item).

Time frame: 4 weeks

Population: The baseline vomiting group subpopulation was defined as all subjects who reported at least 1 episode of vomiting during the screening period and consisted of 101 of 141 (72%) patients of the ITT population.

The Patient Global Impression of Change (PGI-C) is a patient reported questionnaire with a 7-point rating scale where the participant rates his/her own improvement in overall symptoms relative to the baseline assessment. Is is rated as 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse. Higher scores indicate a worse outcome.

Time frame: 4 weeks

Population: The baseline vomiting group subpopulation was defined as all subjects who reported at least 1 episode of vomiting during the screening period and consisted of 101 of 141 (72%) patients of the ITT population.