Gastroparesis
Conditions
Keywords
gastroparesis, early satiety, stomach, buspirone, 5-HT 1a receptor agonist
Brief summary
This study evaluates whether the study medication, buspirone, an antianxiety drug, improves the symptoms of gastroparesis in patients with gastroparesis symptoms and at least moderately severe symptoms of fullness and/or inability to eat a full meal. Half the patients will receive buspirone and half the patients will receive a placebo.
Detailed description
This is a multi-center, randomized, double-masked, placebo-controlled, parallel treatment groups phase 2 trial to determine the effect of buspirone, a 5-hydroxytryptamine (5-HT) 1a receptor agonist, on early satiety and postprandial fullness in participants with symptoms of gastroparesis and with at least moderately severe symptoms of early satiety and/or postprandial fullness. After enrollment, participants aged 18-75 years will be treated with buspirone (10 mg three times per day) or a matching placebo for 4 weeks, followed by a 2-week post-treatment washout period. The primary outcome for the study is 4-week change (week 4 minus baseline) in the 4-item postprandial fullness/early satiety subscore (higher scores indicate worse symptoms) from the Patient Assessment of Gastrointestinal Disorders Symptom Severity Index (PAGI-SYM) Gastroparesis Cardinal Symptom Index (GCSI). We hypothesize that buspirone treatment will improve symptoms of postprandial fullness/early satiety compared to treatment with placebo, as indicated by a lower (smaller, more negative) 4-week change in the postprandial fullness/early satiety subscore in the buspirone arm compared to the placebo arm; change for a participant will be calculated as subscore at 4-weeks minus subscore at baseline.
Interventions
DRUGBuspirone
Buspirone tablet
DRUGPlacebo
Sugar pill manufactured to mimic buspirone 10 mg tablet
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Texas Tech University Health Sciences Center, El Paso
Johns Hopkins University
Temple University
University of Louisville
Wake Forest University
Massachusetts General Hospital
Johns Hopkins Bloomberg School of Public Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Participants, all clinic staff and the investigators will be masked as to whether the participant is receiving buspirone or the placebo. The study drug will be over encapsulated in a size 0 gelatin capsule with partial filler to be identical to the placebo capsule, which contains only filler. The random treatment assignment will consist of a numbered study drug bottle; each bottle number will be unique and each participant will be assigned a specific bottle number, which is labelled: Buspirone or placebo 10 mg. with directions. The randomization scheme will assign participants in randomly permuted blocks of assignments stratified by clinical center. The randomization plan will be prepared and administered centrally via a secure web application by the Scientific Data Research Center.
Intervention model description
BESST is a multi-center, randomized, placebo-controlled, double-masked, parallel treatment groups phase 2 trial with half the participants receiving the study drug, buspirone, and half receiving the placebo.
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Age 18 to 85 years of age at initial screening interview * Symptoms compatible with gastroparesis or other functional gastric disorder for at least 3 months (does not have to be contiguous) prior to initial screening interview * Diagnosis of either diabetic or idiopathic gastroparesis * Delayed or normal gastric emptying retention on screening 4-hour Gastric Emptying Scintigraphy test * Symptoms of gastroparesis measured by the 9-item PAGI-SYM Gastroparesis Cardinal Symptom Index (GCSI) total score \> 2.0 at enrollment * Symptomatic with postprandial fullness/early satiety severity at enrollment using the PAGI-SYM GCSI post-prandial fullness/early satiety subscore ≥ 3 * Upper endoscopy or upper GI series without ulcers or mass lesions in the 2 years prior to enrollment
Exclusion criteria
* Post-surgical gastroparesis, including prior pyloromyotomy, pyloric resection, vagotomy, bariatric surgery or post-Nissen fundoplication * Another active disorder which could explain symptoms in the opinion of the investigator * Concurrent use of opiate narcotic analgesics more than 3 days per week * Significant hepatic injury as defined by alanine aminotransferase (ALT) elevation of greater than twice the Upper Limit of Normal (ULN) or a Child-Pugh score of 10 or greater * Significant renal impairment as defined by serum creatinine \> 3.0 * Uncontrolled diabetes defined as HbA1c (%) of 10% or more within 60 days of enrollment * Allergy to buspirone * Concurrent or prior use (within 30 days) of monoamine oxidase (MAO) inhibitors * Concurrent or prior use (within 30 days) of benzodiazepines * Concurrent or prior use (within 30 days) of buspirone, warfarin, haloperidol, and drugs to treat seizures (e.g., phenytoin and carbamazepine) * Women breast feeding or known to be pregnant * Any other condition, which in the opinion of the investigator would impede compliance or hinder completion of the study * Failure to give informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 4-Week Change in the Postprandial Fullness and Early Satiety Symptoms Severity | baseline and 4-weeks | The outcome is assessed using the self-reported early satiety/postprandial fullness subscore (ES/PPF), which is computed as the average of 4 scores for 4-items on the Gastroparesis Cardinal Symptom Index (GCSI) survey: stomach fullness, inability to finish a normal-sized meal, feeling excessively full after meals, and loss of appetite. Each item is scored from 0 (no) to 5 (very severe) symptoms in the past 2-weeks; the subscore ranges from 0 to 5. The change is computed as the subscore at 4-weeks minus the baseline subscore. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 4-Week Change in Vomiting Symptom Severity | baseline and 4-weeks | The outcome is assessed using self-reported assessment of vomiting severity in the prior 2-weeks using the Gastroparesis Cardinal Symptom Index (GCSI) survey. The item is scored from 0 (no) to 5 (very severe) symptoms; the change is computed as the score at 4-weeks minus the baseline score. A negative change indicates improvement in vomiting severity. |
| 4-Week Change in Participant's Rating of Symptom Relief | baseline and 4-weeks | The outcome is assessed using the participant-rated Clinical Patient Grading Assessment Scale (CPGAS) score which is scored from -3 (very considerably worse) to 3 (completely better) in the past week compared to the way the participant usually feels. The change is computed as the score at 4-weeks minus the baseline score. A positive change indicates patient feeling better. |
| 4-Week Change in Severity of Somatic Symptoms | baseline and 4-weeks | The outcome is assessed using the self-reported Patient Health Questionnaire 15 Somatic Symptom Severity Scale (PHQ-15) total somatization score (ranges from 0 -30, with 30 being most bothered by symptoms in prior 4-weeks), calculated as the sum of 15-items, each scored from 0 (not bothered at all) to 2 (bothered a lot) by somatic symptoms in the prior 4-weeks. The change is computed as the score at 4-weeks minus the baseline score. A negative change indicates being less bothered by the symptoms. |
| 4-Week Change in Depression | baseline and 4-weeks | The outcome is assessed using the self-reported Hospital Anxiety and Depression Scale (HADS) depression subscore, calculated as the sum of 7 items, each scored from 0 (not at all) to 3 (most of the time). The change is computed as the subscore at 4-weeks minus the baseline subscore. A negative change indicates reduced depression. |
| 4-Week Change in Anxiety | baseline and 4-weeks | The outcome is assessed using the self-reported Hospital Anxiety and Depression Scale (HADS) anxiety subscore, calculated as the sum of 7-items, each scored from 0 (not at all) to 3 (most of the time). The change is computed as the subscore at 4-weeks minus the baseline subscore. A negative change indicates reduced anxiety at 4-weeks. |
| 4-Week Change Overall Quality of Health Due to Gastroparesis Issues | baseline and 4-weeks | The outcome is assessed using the self-reported Patient Assessment of Upper Gastrointestinal Disorders-Quality of Life (PAGI-QOL) total score which comprises 30 items scored from 0 (none of the time) to 5 (all of the time) the participant's QOL has been affected by their gastrointestinal issues in the prior two weeks. The total score is the mean of the 5 subscale scores and ranges from 0 (lowest QOL) to 5 (highest QOL) in past 2-weeks. The change is computed as the score at 4-weeks minus the baseline score. A positive change indicates improved QOL. |
| 4-Week Change in Overall Mental Quality of Life (QOL) | baseline and 4-weeks | The outcome is assessed using the self-reported 36-item Short Form Health Survey (SF-36v2) mental health QOL component score. The score ranges from 0 (poorest) to 100 (highest) QOL. The change is computed as the score at 4-weeks minus the baseline score. A positive change indicates improved mental QOL. |
| 4-Week Change in Overall Physical Quality of Life (QOL) | baseline and 4-weeks | The outcome is assessed using the self-reported 36-item Short Form Health Survey (SF-36v2) physical health QOL component score. The score ranges from 0 (poorest) to 100 (highest) QOL. The change is computed as the score at 4-weeks minus the baseline score. A positive change indicates improved Physical QOL. |
| 4-Week Change in Gastric Retention | baseline and 4-weeks | The outcome is assessed using the percent of gastric retention at 4-hours from the Gastric Emptying Scintigraphy (GES) test. The change is computed as the percent retention at 4-weeks minus the baseline percent retention. % retention is the amount of food remaining in the stomach at 4-hours of the GES test and ranges from 0% (no food) to 100% (all of the food). |
| Change at 4-weeks in the Intragastric Meal Distribution (IMD) | baseline and 4-weeks | The Intragastric meal distribution (IMD) is assessed at baseline and 4-weeks during the Gastric Emptying Scintigraphy Test. The ratio of gastric counts of the meal in the proximal stomach to the distal stomach is used to compute the Intragastric meal distribution (IMD) which can be used as an indirect measure of Fundic Accommodation. |
| Change From Baseline at 4-weeks in the Water Load Satiety Test (WLST) | baseline and 4-weeks | The Water Load Satiety Test (WLST) is the amount of water a patient can consume until full in 5 minutes. The volume of water is recorded. The change is computed as the volume of water ingested at baseline subtracted from the amount of water ingested at 4-weeks. A positive change indicates that the patient can ingest more water at 4-weeks than at baseline. |
| 4-Week Change in Stomach Fullness Symptom Severity | baseline and 4-weeks | The outcome is assessed using self-reported assessment of stomach fullness severity in the prior 2-weeks using the Gastroparesis Cardinal Symptoms Index (GCSI) survey. The item is scored from 0 (no) to 5 (very severe) symptoms; the change is computed as the score at 4-weeks minus the baseline score. |
| 4-Week Change in Excessive Fullness Symptom Severity | baseline and 4-weeks | The outcome is assessed using self-reported assessment of feeling excessively full after meals severity in the prior 2-weeks using the Gastroparesis Cardinal Symptom Index (GCSI) survey. The item is scored from 0 (no) to 5 (very severe) symptoms; the change is computed as the score at 4-weeks minus the baseline score. |
| 4-Week Change in Inability to Finish a Normal-sized Meal Symptom Severity | baseline and 4-weeks | The outcome is assessed using self-reported assessment of inability to finish a normal-sized meal severity in the prior 2-weeks using the Gastroparesis Cardinal Symptom Index (GCSI) survey. The item is scored from 0 (no) to 5 (very severe) symptoms; the change is computed as the score at 4-weeks minus the baseline score. A negative change indicates symptom improvement. |
| 4-Week Change in Loss of Appetite Symptom Severity | baseline and 4-weeks | The outcome is assessed using self-reported assessment of loss of appetite severity in the prior 2-weeks using the Gastroparesis Cardinal Symptom Index (GCSI) survey. The item is scored from 0 (no) to 5 (very severe) symptoms; the change is computed as the score at 4-weeks minus the baseline score. A negative change indicates symptom improvement. |
| 4-Week Change in Total Overall GCSI Symptom Severity | baseline and 4-weeks | The outcome is assessed using the self-reported Gastroparesis Cardinal Symptom Index (GCSI) total score, which is computed as the average of the 3 subscores on the GCSI survey: 3-item early satiety/postprandial fullness subscore, the nausea/vomiting subscore (average of 3-items: nausea, retching, vomiting), and bloating subscore (average of 2-items: bloating, stomach visibly larger). Each item is scored from 0 (no) to 5 (very severe) symptoms in the past 2-weeks; the total score ranges from 0 to 5. The change is computed as the total score at 4-weeks minus the baseline total score. A negative change indicates improved symptoms. |
| 4-Week Change in Nausea, Vomiting and Retching Symptoms Severity | baseline and 4-weeks | The outcome is assessed using the self-reported nausea/vomiting subscore, which is computed as the average of 3 scores for 3-items on the Gastrointestinal Cardinal Symptom Index (GCSI) survey: nausea, retching, vomiting. Each item is scored from 0 (no) to 5 (very severe) symptoms in the past 2-weeks. The change is computed as the subscore at 4-weeks minus the baseline subscore. Negative change indicates improvement in symptoms. |
| 4-Week Change in Nausea Symptom Severity | baseline and 4-weeks | The outcome is assessed using self-reported assessment of nausea severity item from the Patient Assessment of Upper Gastrointestinal Disorders Symptom Severity Index (PAGI-SYM) in the prior 2-weeks using the Gastroparesis Cardinal Symptom Index (GCSI) survey. The item is scored from 0 (no) to 5 (very severe) symptoms; the change is computed as the score at 4-weeks minus the baseline score. |
| 4-Week Change in Bloating and Stomach Distention Symptoms Severity | baseline and 4-weeks | The outcome is assessed using the self-reported bloating subscore, which is computed as the average of 2 scores for 2-items on the Gastroparesis Cardinal Symptom Index (GCSI) survey: bloating, stomach visibly larger. Each item is scored from 0 (no) to 5 (very severe) symptoms in the past 2-weeks; the subscore ranges from 0 to 5. The change is computed as the subscore at 4-weeks minus the baseline subscore. A negative value for change indicates improvement in symptoms. |
| 4-Week Change in Bloating Symptom Severity | baseline and 4-weeks | The outcome is assessed using self-reported assessment of bloating severity in the prior 2-weeks using the Gastroparesis Cardinal Symptom Index (GCSI) survey. The item is scored from 0 (no) to 5 (very severe) symptoms; the change is computed as the score at 4-weeks minus the baseline score. A negative change indicates symptom improvement. |
| 4-Week Change in Upper Abdominal Pain and Discomfort Symptoms Severity | baseline and 4-weeks | The outcome is assessed using the self-reported upper abdominal pain subscore, which is computed as the average of 2 scores for 2-items on the Patient Assessment of Upper Gastrointestinal Disorders-Symptom Severity Index (PAGI-SYM) survey: upper abdominal pain, upper abdominal discomfort. Each item is scored from 0 (no) to 5 (very severe) symptoms in the past 2-weeks; the subscore ranges from 0 to 5. The change is computed as the subscore at 4-weeks minus the baseline subscore. |
| 4-Week Change in Upper Abdominal Pain Symptom Severity | baseline and 4-weeks | The outcome is assessed using self-reported assessment of upper abdominal pain severity in the prior 2-weeks using the Patient Assessment of Upper Gastrointestinal Disorders Symptom Severity Index (PAGI-SYM) survey. The item is scored from 0 (no) to 5 (very severe) symptoms; the change is computed as the score at 4-weeks minus the baseline score. A negative change indicates symptom improvement. |
| 4-Week Change in Gastroesophageal (GERD) Symptoms Severity | baseline and 4-weeks | The outcome is assessed using the self-reported GERD subscore, which is computed as the average of 7 scores for 7-items on the Patient Assessment of Gastrointestinal Disorders Symptom Severity Index (PAGI-SYM) survey: heartburn during the day, heartburn when lying down, feeling of discomfort inside chest during the day, feeling of discomfort inside chest during sleep, regurgitation or reflux during the day, regurgitation when lying down, bitter, acid or sour taste in mouth. Each item is scored from 0 (no) to 5 (very severe) symptoms in the past 2-weeks; the subscore ranges from 0 to 5. The change is computed as the subscore at 4-weeks minus the baseline subscore. |
| 4-Week Change in Gastrointestinal Symptoms Rating Scale (GSRS) Global Score | baseline and 4-weeks | The outcome is assessed using the self-reported GSRS total score which is computed as the mean of the 15 item scores on the Gastrointestinal Symptom Rating Scale (GSRS) survey. Each item is scored from 1 (no discomfort) to 7 (very severe discomfort) of the symptom in the past week. The change is computed as the score at 4-weeks minus the baseline score. A negative change indicates symptom improvement. |
Other
| Measure | Time frame | Description |
|---|---|---|
| 4-Week Change in Aspartate Aminotransferase (ALT) | baseline and 4-weeks | This safety outcome is computed by subtracting the baseline level of Alanine Aminotransferase (ALT) (U/L) from the 4-week level. |
| 4-Week Change in Creatinine | baseline and 4-weeks | This safety outcome is computed by subtracting the baseline level of creatinine (mg/dL) from the 4-week level. |
| 4-Week Change in Fasting Glucose | baseline and 4-weeks | This safety outcome is computed by subtracting the baseline level of glucose (mg/dL) from the 4-week level. |
| Assessment of Adverse Events Over 4-Weeks | over 4-weeks | This safety outcome is the frequency over the 4-weeks of the study of all reported adverse events using the v5.0 CTCAE classification system. |
| Assessment of the Severity of Adverse Events Over 4-Weeks | over 4-weeks | This safety outcome is the frequency over the 4-weeks of the study of all reported adverse events' severity grade as classified by the NCI's Common Terminology Criteria for Adverse Events (CTCAE v5.0). For the patient with 2 AE's, the AE with the maximum severity is reported. |
| Serious Adverse Events | over 4 weeks of treatment | Serious Adverse Event (SAE) defined by the FDA as an event meeting one or more of the following criteria; inpatient hospitalization or prolonged existing hospitalization; persistent or significant incapacity or substantial disruption of ability to conduct normal life functions; jeopardized patient and required medical or surgical intervention to prevent a serious event; or congenital anomaly or birth defect. |
| Total Number of Hospitalizations Over 4-weeks of Treatment | over the 4-weeks of the trial | Hospitalization events by treatment arm were reported on the Adverse Event Case-Report form at each visit and also at time of occurrence and tabulated at end of treatment visit for comparison between placebo and buspirone arms. |
| Adverse Events by Body Classification System by Treatment Group During the Trial | over 4-weeks of treatment | Adverse events were reported on the Adverse Event Report form by the principal investigator at each clinic site using the CTCAE v5 classification system. |
| 4-Week Cardiac Rhythm | baseline and 4-weeks | This safety outcome is computed from the results of an electrocardiogram (ECG) QTc interval at 4-weeks measured in milliseconds (msec). |
| 4-Week Change in Weight | baseline and 4-weeks | This safety outcome is computed by subtracting the weight (kg) at baseline from the weight (kg) at 4-weeks |
Countries
United States
Participant flow
Recruitment details
131 adult participants with gastroparesis or gastroparesis-like 28, symptoms with at least moderately severe symptoms of early satiety and post-prandial fullness and a normal endoscopy were recruited at 6 tertiary clinic sites located in the U.S. between August 2019 and February 2022. The first participant was enrolled August 27, 2019 and the last participant was enrolled February 28, 2022.
Pre-assignment details
Of the 131 participants assessed for eligibility, 96 met eligibility criteria and provided informed consent and were randomized to treatment (47 to Buspirone arm and 49 to Placebo arm).
Participants by arm
| Arm | Count |
|---|---|
| Buspirone Buspirone HCl 10 mg capsule orally three times daily, 30 minutes before each meal, for 4-weeks
Buspirone: Buspirone tablet | 47 |
| Placebo Placebo capsule orally three times daily, 30 minutes before each meal, for 4-weeks; manufactured to look identical to buspirone capsule
Placebo: Sugar pill manufactured to mimic buspirone 10 mg tablet | 49 |
| Total | 96 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Did not complete the f4 visit | 3 | 7 |
| Overall Study | Lost to Follow-up | 5 | 3 |
Baseline characteristics
| Characteristic | Buspirone | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 43.0 years STANDARD_DEVIATION 15.8 | 44.2 years STANDARD_DEVIATION 15 | 43.6 years STANDARD_DEVIATION 15.3 |
| ANMS Gastroparesis Cardinal Symptom Index Daily Diary Early satiety severity | 2.56 units on a scale STANDARD_DEVIATION 0.78 | 2.59 units on a scale STANDARD_DEVIATION 0.86 | 2.57 units on a scale STANDARD_DEVIATION 0.94 |
| ANMS Gastroparesis Cardinal Symptom Index Daily Diary Excessive fullness severity | 2.40 units on a scale STANDARD_DEVIATION 0.98 | 2.77 units on a scale STANDARD_DEVIATION 0.98 | 2.74 units on a scale STANDARD_DEVIATION 0.94 |
| ANMS Gastroparesis Cardinal Symptom Index Daily Diary Fullness/early satiety subscale | 2.62 units on a scale STANDARD_DEVIATION 0.94 | 2.68 units on a scale STANDARD_DEVIATION 0.86 | 2.65 units on a scale STANDARD_DEVIATION 0.9 |
| Anti-depressant | 22 Participants | 22 Participants | 44 Participants |
| Antiemetic | 31 Participants | 25 Participants | 56 Participants |
| Anxiolytic | 1 Participants | 0 Participants | 1 Participants |
| Bloating severity | 4.4 units on a scale STANDARD_DEVIATION 0.9 | 4.0 units on a scale STANDARD_DEVIATION 1.1 | 4.2 units on a scale STANDARD_DEVIATION 1 |
| Bloating subscale | 4.2 units on a scale STANDARD_DEVIATION 1 | 3.9 units on a scale STANDARD_DEVIATION 1 | 4.1 units on a scale STANDARD_DEVIATION 1 |
| Body Mass Index (BMI) | 29.5 kg/m^2 STANDARD_DEVIATION 7.5 | 29.8 kg/m^2 STANDARD_DEVIATION 7.3 | 29.7 kg/m^2 STANDARD_DEVIATION 7.4 |
| Diabetes Type 1 | 3 Participants | 6 Participants | 9 Participants |
| Diabetes Type 2 | 13 Participants | 15 Participants | 28 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 13 Participants | 17 Participants | 30 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 34 Participants | 32 Participants | 66 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Excessive fullness severity | 4.2 units on a scale STANDARD_DEVIATION 0.9 | 4.3 units on a scale STANDARD_DEVIATION 0.7 | 4.3 units on a scale STANDARD_DEVIATION 0.8 |
| Fullness/early satiety subscale | 4.0 units on a scale STANDARD_DEVIATION 0.6 | 4.0 units on a scale STANDARD_DEVIATION 0.6 | 4.0 units on a scale STANDARD_DEVIATION 0.6 |
| Gastric Emptying scintigraphy (GES) Delayed gastric emptying | 26 Participants | 22 Participants | 48 Participants |
| Gastric Emptying scintigraphy (GES) Not delayed gastric emptying | 20 Participants | 25 Participants | 45 Participants |
| Gastric Emptying scintigraphy (GES) Rapid gastric emptying | 1 Participants | 2 Participants | 3 Participants |
| Gastroesophageal Reflux (GERD) subscale | 2.1 units on a scale STANDARD_DEVIATION 1.4 | 2.3 units on a scale STANDARD_DEVIATION 1.2 | 2.2 units on a scale STANDARD_DEVIATION 1.3 |
| Gastrointestinal Symptom Rating Scale (GSRS) | 3.8 units on a scale STANDARD_DEVIATION 1 | 3.7 units on a scale STANDARD_DEVIATION 1.1 | 3.8 units on a scale STANDARD_DEVIATION 1 |
| Gastroparesis Cardinal Symptom Index (GCSI), total score | 3.6 units on a scale STANDARD_DEVIATION 0.7 | 3.5 units on a scale STANDARD_DEVIATION 0.6 | 3.5 units on a scale STANDARD_DEVIATION 0.6 |
| Hospital Anxiety and Depression Scale (HADS) HADS-A total score | 9.3 units on a scale STANDARD_DEVIATION 4.5 | 9.1 units on a scale STANDARD_DEVIATION 4.8 | 9.2 units on a scale STANDARD_DEVIATION 4.6 |
| Hospital Anxiety and Depression Scale (HADS) HADS-D total score | 6.7 units on a scale STANDARD_DEVIATION 5.1 | 6.8 units on a scale STANDARD_DEVIATION 4.7 | 6.8 units on a scale STANDARD_DEVIATION 4.9 |
| Intra-gastric meal distribution (IMD) Borderline (0.568 - 0.643) | 0 Participants | 3 Participants | 3 Participants |
| Intra-gastric meal distribution (IMD) Impaired (<0.568) | 4 Participants | 5 Participants | 9 Participants |
| Intra-gastric meal distribution (IMD) Normal (0.644 - 1.00) | 27 Participants | 25 Participants | 52 Participants |
| Loss of appetite severity | 3.6 units on a scale STANDARD_DEVIATION 1.3 | 3.5 units on a scale STANDARD_DEVIATION 1.2 | 3.5 units on a scale STANDARD_DEVIATION 1.2 |
| Married | 16 Participants | 21 Participants | 37 Participants |
| Narcotic (3X/week or less) | 2 Participants | 4 Participants | 6 Participants |
| Nausea severity | 3.6 units on a scale STANDARD_DEVIATION 1.3 | 3.6 units on a scale STANDARD_DEVIATION 1.2 | 3.6 units on a scale STANDARD_DEVIATION 1.3 |
| Nausea/vomiting subscale | 2.5 units on a scale STANDARD_DEVIATION 1.3 | 2.4 units on a scale STANDARD_DEVIATION 1.3 | 2.5 units on a scale STANDARD_DEVIATION 1.3 |
| Neuropathic or pain modulator, anti-seizure, or other psychiatric medication | 28 Participants | 31 Participants | 59 Participants |
| Overweight to obese (BMI>/=25 kg/m^2) | 31 Participants | 37 Participants | 68 Participants |
| PAGI-QOL disease-specific Quality of Life (QOL) Total Score | 2.3 units on a scale STANDARD_DEVIATION 1.1 | 2.4 units on a scale STANDARD_DEVIATION 1.1 | 2.4 units on a scale STANDARD_DEVIATION 1.1 |
| Patient Health Questionnaire somatization severity scale (PHQ-15) | 14.7 units on a scale STANDARD_DEVIATION 5 | 14.9 units on a scale STANDARD_DEVIATION 4.1 | 14.8 units on a scale STANDARD_DEVIATION 4.5 |
| Predominant symptom cluster Bloating or distended stomach | 14 Participants | 10 Participants | 24 Participants |
| Predominant symptom cluster Early satiety or loss of appetite | 2 Participants | 4 Participants | 6 Participants |
| Predominant symptom cluster Excessive fullness | 4 Participants | 13 Participants | 17 Participants |
| Predominant symptom cluster Lower abdominal pain or discomfort | 4 Participants | 1 Participants | 5 Participants |
| Predominant symptom cluster Nausea or vomiting or retching | 15 Participants | 13 Participants | 28 Participants |
| Predominant symptom cluster Upper abdominal pain or discomfort | 5 Participants | 1 Participants | 6 Participants |
| Proton pump inhibitors | 35 Participants | 34 Participants | 69 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 5 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 43 Participants | 41 Participants | 84 Participants |
| Retching severity | 2.1 units on a scale STANDARD_DEVIATION 1.7 | 1.8 units on a scale STANDARD_DEVIATION 1.6 | 2.0 units on a scale STANDARD_DEVIATION 1.6 |
| Sex: Female, Male Female | 43 Participants | 45 Participants | 88 Participants |
| Sex: Female, Male Male | 4 Participants | 4 Participants | 8 Participants |
| SF-36 Quality of Life (QOL) Mental component summary score | 37.9 units on a scale STANDARD_DEVIATION 15.6 | 41.3 units on a scale STANDARD_DEVIATION 13.8 | 39.6 units on a scale STANDARD_DEVIATION 14.7 |
| SF-36 Quality of Life (QOL) Physical component summary score | 33.7 units on a scale STANDARD_DEVIATION 8.2 | 33.3 units on a scale STANDARD_DEVIATION 9 | 33.5 units on a scale STANDARD_DEVIATION 8.6 |
| Stomach distention severity | 4.0 units on a scale STANDARD_DEVIATION 1.2 | 3.9 units on a scale STANDARD_DEVIATION 1.1 | 4.0 units on a scale STANDARD_DEVIATION 1.1 |
| Stomach fullness severity | 4.2 units on a scale STANDARD_DEVIATION 0.8 | 4.2 units on a scale STANDARD_DEVIATION 0.7 | 4.2 units on a scale STANDARD_DEVIATION 0.7 |
| Unable to finish meal severity | 4.0 units on a scale STANDARD_DEVIATION 1 | 4.0 units on a scale STANDARD_DEVIATION 0.9 | 4.0 units on a scale STANDARD_DEVIATION 0.9 |
| Upper abdominal pain subscale | 3.3 units on a scale STANDARD_DEVIATION 1.3 | 3.0 units on a scale STANDARD_DEVIATION 1.2 | 3.1 units on a scale STANDARD_DEVIATION 1.2 |
| Vomiting severity | 1.9 units on a scale STANDARD_DEVIATION 1.8 | 1.8 units on a scale STANDARD_DEVIATION 1.7 | 1.8 units on a scale STANDARD_DEVIATION 1.7 |
| Waist circumfence | 98.1 centimeter STANDARD_DEVIATION 22.2 | 98.2 centimeter STANDARD_DEVIATION 19.6 | 98.1 centimeter STANDARD_DEVIATION 20.8 |
| Water load test, consumed low volume (<238 mL) | 9 Participants | 10 Participants | 19 Participants |
| Water load test, volume consumed | 415.9 mL STANDARD_DEVIATION 217 | 401.7 mL STANDARD_DEVIATION 198 | 408.5 mL STANDARD_DEVIATION 206.3 |
| Weight | 78.1 kilogram STANDARD_DEVIATION 21.2 | 80.2 kilogram STANDARD_DEVIATION 22.2 | 79.2 kilogram STANDARD_DEVIATION 21.6 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 47 | 0 / 49 |
| other Total, other adverse events | 11 / 47 | 7 / 49 |
| serious Total, serious adverse events | 1 / 47 | 1 / 49 |
Outcome results
Primary
4-Week Change in the Postprandial Fullness and Early Satiety Symptoms Severity
The outcome is assessed using the self-reported early satiety/postprandial fullness subscore (ES/PPF), which is computed as the average of 4 scores for 4-items on the Gastroparesis Cardinal Symptom Index (GCSI) survey: stomach fullness, inability to finish a normal-sized meal, feeling excessively full after meals, and loss of appetite. Each item is scored from 0 (no) to 5 (very severe) symptoms in the past 2-weeks; the subscore ranges from 0 to 5. The change is computed as the subscore at 4-weeks minus the baseline subscore.
Time frame: baseline and 4-weeks
Population: All participants assigned to the arm with data for the outcome available at 4-weeks.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Buspirone | 4-Week Change in the Postprandial Fullness and Early Satiety Symptoms Severity | -1.16 score on a scale | Standard Deviation 1.25 |
| Placebo | 4-Week Change in the Postprandial Fullness and Early Satiety Symptoms Severity | -1.03 score on a scale | Standard Deviation 1.19 |
Comparison: Primary outcome analysis uses a difference of differences analysis between Buspirone compared to the Placebo arm in which the adjusted mean difference of differences, Wald 95% Confidence interval and 2-sided P values are determined from a Wald Chi-Square test. Adjusted mean difference of differences (DoD) from baseline were computed using ANCOVA, regressing change from baseline to 4-weeks on treatment group and baseline value of the outcome. Negative change indicates symptom improvement.p-value: 0.6995% CI: [-0.68, 0.45]ANCOVA
Comparison: Sensitivity analysis of change from a baseline in ES/PPF (Early Satiety/Postprandial Fullness subscore) using all completers: 39 participants in Buspirone arm, 39 participants in placebo arm.p-value: 0.6295% CI: [-0.65, 0.39]ANCOVA
Comparison: Sensitivity analyses: change in ES/PPF in treatment adherent patients: 23 participants in Buspirone arm, 29 patients in placebo arm.p-value: 0.6295% CI: [-0.89, 0.38]ANCOVA
Secondary
4-Week Change in Anxiety
The outcome is assessed using the self-reported Hospital Anxiety and Depression Scale (HADS) anxiety subscore, calculated as the sum of 7-items, each scored from 0 (not at all) to 3 (most of the time). The change is computed as the subscore at 4-weeks minus the baseline subscore. A negative change indicates reduced anxiety at 4-weeks.
Time frame: baseline and 4-weeks
Population: Participants in each arm with HADS anxiety data at 4-weeks. 1 Placebo patient did not report a HADS anxiety subscale score at 4 -weeks.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Buspirone | 4-Week Change in Anxiety | -1.27 units on a scale | Standard Deviation 4.82 |
| Placebo | 4-Week Change in Anxiety | -2.03 units on a scale | Standard Deviation 3.94 |
Comparison: Adjusted mean difference of differences (DoD) from baseline were computed using ANCOVA, regressing change from baseline to 4-weeks on treatment group and baseline value of the HADS anxiety total score. 95% Wald Confidence Intervals are reported; P (2-sided) determined from a Wald Chi-Square testp-value: 0.495% CI: [-1.02, 2.54]ANCOVA
Secondary
4-Week Change in Bloating and Stomach Distention Symptoms Severity
The outcome is assessed using the self-reported bloating subscore, which is computed as the average of 2 scores for 2-items on the Gastroparesis Cardinal Symptom Index (GCSI) survey: bloating, stomach visibly larger. Each item is scored from 0 (no) to 5 (very severe) symptoms in the past 2-weeks; the subscore ranges from 0 to 5. The change is computed as the subscore at 4-weeks minus the baseline subscore. A negative value for change indicates improvement in symptoms.
Time frame: baseline and 4-weeks
Population: All participants assigned to the arm with a 4-week visit data for the bloating subscore.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Buspirone | 4-Week Change in Bloating and Stomach Distention Symptoms Severity | -1.36 score on a scale | Standard Deviation 1.42 |
| Placebo | 4-Week Change in Bloating and Stomach Distention Symptoms Severity | -0.95 score on a scale | Standard Deviation 1.27 |
Comparison: Adjusted mean difference of differences (DoD) from baseline were computed using ANCOVA, regressing change from baseline to 4-weeks on treatment group and baseline value of the outcome. Wald 95% Confidence Limits (CI) are reported; P (2-sided) determined from a Wald Chi-Square test.p-value: 0.1695% CI: [-0.99, 0.16]ANCOVA
Secondary
4-Week Change in Bloating Symptom Severity
The outcome is assessed using self-reported assessment of bloating severity in the prior 2-weeks using the Gastroparesis Cardinal Symptom Index (GCSI) survey. The item is scored from 0 (no) to 5 (very severe) symptoms; the change is computed as the score at 4-weeks minus the baseline score. A negative change indicates symptom improvement.
Time frame: baseline and 4-weeks
Population: All participants assigned to the treatment arm with a 4-week visit and data for bloating severity.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Buspirone | 4-Week Change in Bloating Symptom Severity | -1.34 score on a scale | Standard Deviation 1.46 |
| Placebo | 4-Week Change in Bloating Symptom Severity | -0.69 score on a scale | Standard Deviation 1.18 |
Comparison: Adjusted mean difference of differences (DoD) from baseline were computed using ANCOVA, regressing change from baseline to 4-weeks on treatment group and baseline value of the outcome. Wald 95% Confidence Limits (CI) are reported; P (2-sided) determined from a Wald Chi-Square test.p-value: 0.0395% CI: [-1.23, -0.08]ANCOVA
Secondary
4-Week Change in Depression
The outcome is assessed using the self-reported Hospital Anxiety and Depression Scale (HADS) depression subscore, calculated as the sum of 7 items, each scored from 0 (not at all) to 3 (most of the time). The change is computed as the subscore at 4-weeks minus the baseline subscore. A negative change indicates reduced depression.
Time frame: baseline and 4-weeks
Population: Participants in each arm with HADS data at 4-weeks. 1 Placebo patient did not have HADS data at 4-weeks.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Buspirone | 4-Week Change in Depression | 0.42 units on a scale | Standard Deviation 4.06 |
| Placebo | 4-Week Change in Depression | -1.43 units on a scale | Standard Deviation 3.91 |
Comparison: Adjusted mean difference of differences (DoD) from baseline were computed using ANCOVA, regressing change from baseline to 4-weeks on treatment group and baseline value of the HADS depression score.p-value: 0.0295% CI: [0.33, 3.38]ANCOVA
Secondary
4-Week Change in Excessive Fullness Symptom Severity
The outcome is assessed using self-reported assessment of feeling excessively full after meals severity in the prior 2-weeks using the Gastroparesis Cardinal Symptom Index (GCSI) survey. The item is scored from 0 (no) to 5 (very severe) symptoms; the change is computed as the score at 4-weeks minus the baseline score.
Time frame: baseline and 4-weeks
Population: All participants assigned to the arm with a 4-week visit and data for excessive fullness severity.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Buspirone | 4-Week Change in Excessive Fullness Symptom Severity | -1.14 score on a scale | Standard Deviation 1.56 |
| Placebo | 4-Week Change in Excessive Fullness Symptom Severity | -0.99 score on a scale | Standard Deviation 1.3 |
Comparison: Adjusted mean difference of differences (DoD) from baseline were computed using ANCOVA, regressing change from baseline to 4-weeks on treatment group and baseline value of the outcome. Wald 95% Confidence Limits (CI) are reported; P (2-sided) determined from a Wald Chi-Square test.p-value: 0.6495% CI: [-0.76, 0.47]ANCOVA
Secondary
4-Week Change in Gastric Retention
The outcome is assessed using the percent of gastric retention at 4-hours from the Gastric Emptying Scintigraphy (GES) test. The change is computed as the percent retention at 4-weeks minus the baseline percent retention. % retention is the amount of food remaining in the stomach at 4-hours of the GES test and ranges from 0% (no food) to 100% (all of the food).
Time frame: baseline and 4-weeks
Population: All participants assigned to the arm that had 4 week visit data for the GES test at 4-hours.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Buspirone | 4-Week Change in Gastric Retention | 4.24 units on a percentage scale | Standard Deviation 21.19 |
| Placebo | 4-Week Change in Gastric Retention | 2.87 units on a percentage scale | Standard Deviation 21.8 |
Comparison: Adjusted mean difference of differences (DoD) from baseline were computed using ANCOVA regressing change from baseline to 4-weeks on treatment group and baseline value of the outcome. Wald 95% Confidence Intervals are reported. P (2-sided) determined from a Wald Chi-Square test.p-value: 0.7695% CI: [-7.51, 10.25]ANCOVA
Secondary
4-Week Change in Gastroesophageal (GERD) Symptoms Severity
The outcome is assessed using the self-reported GERD subscore, which is computed as the average of 7 scores for 7-items on the Patient Assessment of Gastrointestinal Disorders Symptom Severity Index (PAGI-SYM) survey: heartburn during the day, heartburn when lying down, feeling of discomfort inside chest during the day, feeling of discomfort inside chest during sleep, regurgitation or reflux during the day, regurgitation when lying down, bitter, acid or sour taste in mouth. Each item is scored from 0 (no) to 5 (very severe) symptoms in the past 2-weeks; the subscore ranges from 0 to 5. The change is computed as the subscore at 4-weeks minus the baseline subscore.
Time frame: baseline and 4-weeks
Population: All participants assigned to the arm with 4-week visit data for the GERD subscore.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Buspirone | 4-Week Change in Gastroesophageal (GERD) Symptoms Severity | -0.36 score on a scale | Standard Deviation 1.44 |
| Placebo | 4-Week Change in Gastroesophageal (GERD) Symptoms Severity | -0.45 score on a scale | Standard Deviation 1.01 |
Comparison: Adjusted mean difference of differences (DoD) from baseline were computed using ANCOVA, regressing change from baseline to 4-weeks on treatment group and baseline value of the outcome. Wald 95% Confidence Limits (CI) are reported; P (2-sided) determined from a Wald Chi-Square test.p-value: 0.7395% CI: [-0.42, 0.59]ANCOVA
Secondary
4-Week Change in Gastrointestinal Symptoms Rating Scale (GSRS) Global Score
The outcome is assessed using the self-reported GSRS total score which is computed as the mean of the 15 item scores on the Gastrointestinal Symptom Rating Scale (GSRS) survey. Each item is scored from 1 (no discomfort) to 7 (very severe discomfort) of the symptom in the past week. The change is computed as the score at 4-weeks minus the baseline score. A negative change indicates symptom improvement.
Time frame: baseline and 4-weeks
Population: All participants assigned to the arm with a 4-week visit and data for the GSRS total score.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Buspirone | 4-Week Change in Gastrointestinal Symptoms Rating Scale (GSRS) Global Score | -0.63 units on a scale | Standard Deviation 1.09 |
| Placebo | 4-Week Change in Gastrointestinal Symptoms Rating Scale (GSRS) Global Score | -0.49 units on a scale | Standard Deviation 0.9 |
Comparison: Adjusted mean difference of differences (DoD) from baseline were computed using ANCOVA, regressing change from baseline to 4-weeks on treatment group and baseline value of the outcome. Wald 95% Confidence Limits (CI) are reported; P (2-sided) determined from a Wald Chi-Square test.p-value: 0.595% CI: [-0.55, 0.27]ANCOVA
Secondary
4-Week Change in Inability to Finish a Normal-sized Meal Symptom Severity
The outcome is assessed using self-reported assessment of inability to finish a normal-sized meal severity in the prior 2-weeks using the Gastroparesis Cardinal Symptom Index (GCSI) survey. The item is scored from 0 (no) to 5 (very severe) symptoms; the change is computed as the score at 4-weeks minus the baseline score. A negative change indicates symptom improvement.
Time frame: baseline and 4-weeks
Population: All participants assigned to the arm with a 4-week visit.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Buspirone | 4-Week Change in Inability to Finish a Normal-sized Meal Symptom Severity | -1.27 score on a scale | Standard Deviation 1.55 |
| Placebo | 4-Week Change in Inability to Finish a Normal-sized Meal Symptom Severity | -1.12 score on a scale | Standard Deviation 1.63 |
Comparison: Adjusted mean difference of differences (DoD) from baseline were computed using ANCOVA, regressing change from baseline to 4-weeks on treatment group and baseline value of the outcome. Wald 95% Confidence Limits (CI) are reported; P (2-sided) determined from a Wald Chi-Square test.p-value: 0.6695% CI: [-0.79, 0.5]ANCOVA
Secondary
4-Week Change in Loss of Appetite Symptom Severity
The outcome is assessed using self-reported assessment of loss of appetite severity in the prior 2-weeks using the Gastroparesis Cardinal Symptom Index (GCSI) survey. The item is scored from 0 (no) to 5 (very severe) symptoms; the change is computed as the score at 4-weeks minus the baseline score. A negative change indicates symptom improvement.
Time frame: baseline and 4-weeks
Population: All participants assigned to the arm with a 4-week visit and values for loss of appetite severity.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Buspirone | 4-Week Change in Loss of Appetite Symptom Severity | -1.09 score on a scale | Standard Deviation 1.64 |
| Placebo | 4-Week Change in Loss of Appetite Symptom Severity | -0.96 score on a scale | Standard Deviation 1.62 |
Comparison: Adjusted mean difference of differences (DoD) from baseline were computed using ANCOVA, regressing change from baseline to 4-weeks on treatment group and baseline value of the outcome. Wald 95% Confidence Limits (CI) are reported; P (s-sided) determined from a Wald Chi-Square test.p-value: 0.795% CI: [-0.75, 0.5]ANCOVA
Secondary
4-Week Change in Nausea Symptom Severity
The outcome is assessed using self-reported assessment of nausea severity item from the Patient Assessment of Upper Gastrointestinal Disorders Symptom Severity Index (PAGI-SYM) in the prior 2-weeks using the Gastroparesis Cardinal Symptom Index (GCSI) survey. The item is scored from 0 (no) to 5 (very severe) symptoms; the change is computed as the score at 4-weeks minus the baseline score.
Time frame: baseline and 4-weeks
Population: All participants assigned to the arm with a 4-week visit and data for the nausea severity.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Buspirone | 4-Week Change in Nausea Symptom Severity | -0.75 score on a scale | Standard Deviation 1.4 |
| Placebo | 4-Week Change in Nausea Symptom Severity | -0.70 score on a scale | Standard Deviation 1.51 |
Comparison: Adjusted mean difference of differences (DoD) from baseline were computed using ANCOVA, regressing change from baseline to 4-weeks on treatment group and baseline value of outcome. Wald 95% Confidence Limits (CI) are reported; P (2-sided) determined from a Wald-Chi Square test.p-value: 0.8595% CI: [-0.64, 0.53]ANCOVA
Secondary
4-Week Change in Nausea, Vomiting and Retching Symptoms Severity
The outcome is assessed using the self-reported nausea/vomiting subscore, which is computed as the average of 3 scores for 3-items on the Gastrointestinal Cardinal Symptom Index (GCSI) survey: nausea, retching, vomiting. Each item is scored from 0 (no) to 5 (very severe) symptoms in the past 2-weeks. The change is computed as the subscore at 4-weeks minus the baseline subscore. Negative change indicates improvement in symptoms.
Time frame: baseline and 4-weeks
Population: All participants assigned to the arm with a 4-week visit and data for the nausea/vomiting subscore.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Buspirone | 4-Week Change in Nausea, Vomiting and Retching Symptoms Severity | -0.65 score on a scale | Standard Deviation 1.4 |
| Placebo | 4-Week Change in Nausea, Vomiting and Retching Symptoms Severity | -0.60 score on a scale | Standard Deviation 1.26 |
Comparison: Adjusted mean difference of differences (DoD) from baseline were computed using ANCOVA, regressing change from baseline to 4-weeks on treatment group and baseline value of the outcome. Wald 95% Confidence Limits (CI) are reported; P (2-sided) determined from a Wald Chi-Squares test.p-value: 0.8695% CI: [-0.58, 0.48]ANCOVA
Secondary
4-Week Change in Overall Mental Quality of Life (QOL)
The outcome is assessed using the self-reported 36-item Short Form Health Survey (SF-36v2) mental health QOL component score. The score ranges from 0 (poorest) to 100 (highest) QOL. The change is computed as the score at 4-weeks minus the baseline score. A positive change indicates improved mental QOL.
Time frame: baseline and 4-weeks
Population: All participants in the treatment arm with baseline and mental QOL data at 4-weeks.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Buspirone | 4-Week Change in Overall Mental Quality of Life (QOL) | 1.19 units on a scale | Standard Deviation 10.54 |
| Placebo | 4-Week Change in Overall Mental Quality of Life (QOL) | 3.17 units on a scale | Standard Deviation 11.83 |
Comparison: Adjusted mean difference of differences (DoD) of change in outcome from baseline and 95% Confidence Intervals were computed using ANCOVA, regressing change from baseline to 4-weeks on treatment group and baseline value of outcome. P (2-sided) were determined from a Wald-Chi-Square test.p-value: 0.3695% CI: [-6.2, 2.24]ANCOVA
Secondary
4-Week Change in Overall Physical Quality of Life (QOL)
The outcome is assessed using the self-reported 36-item Short Form Health Survey (SF-36v2) physical health QOL component score. The score ranges from 0 (poorest) to 100 (highest) QOL. The change is computed as the score at 4-weeks minus the baseline score. A positive change indicates improved Physical QOL.
Time frame: baseline and 4-weeks
Population: All participants assigned to the arm with a 4-week visit and data for the Physical QOL summary score.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Buspirone | 4-Week Change in Overall Physical Quality of Life (QOL) | 1.10 units on a scale | Standard Deviation 7.18 |
| Placebo | 4-Week Change in Overall Physical Quality of Life (QOL) | 3.17 units on a scale | Standard Deviation 5.95 |
Comparison: Adjusted mean difference of differences (DoD) from baseline were computed using ANCOVA, regressing change from baseline to 4-weeks on treatment group and baseline value of the outcome. Wald 95% Confidence Limits (CI) are reported; P (2-sided) determined from a Wald Chi-Square test.p-value: 0.1595% CI: [-4.91, 0.76]ANCOVA
Secondary
4-Week Change in Participant's Rating of Symptom Relief
The outcome is assessed using the participant-rated Clinical Patient Grading Assessment Scale (CPGAS) score which is scored from -3 (very considerably worse) to 3 (completely better) in the past week compared to the way the participant usually feels. The change is computed as the score at 4-weeks minus the baseline score. A positive change indicates patient feeling better.
Time frame: baseline and 4-weeks
Population: All participants assigned to the arm with a 4-week visit and data for CPGAS score.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Buspirone | 4-Week Change in Participant's Rating of Symptom Relief | 0.69 units on a scale | Standard Deviation 1.03 |
| Placebo | 4-Week Change in Participant's Rating of Symptom Relief | 0.37 units on a scale | Standard Deviation 1.1 |
Comparison: Adjusted mean difference of differences (DoD) from baseline were computed using ANCOVA, regressing change from baseline to 4-weeks on treatment group and baseline value of the outcome. Wald 95% Confidence Limits (CI) are reported; P (2-sided) determined from a Wald Chi-Square test.p-value: 0.1895% CI: [-0.15, 0.79]ANOVA
Secondary
4-Week Change in Severity of Somatic Symptoms
The outcome is assessed using the self-reported Patient Health Questionnaire 15 Somatic Symptom Severity Scale (PHQ-15) total somatization score (ranges from 0 -30, with 30 being most bothered by symptoms in prior 4-weeks), calculated as the sum of 15-items, each scored from 0 (not bothered at all) to 2 (bothered a lot) by somatic symptoms in the prior 4-weeks. The change is computed as the score at 4-weeks minus the baseline score. A negative change indicates being less bothered by the symptoms.
Time frame: baseline and 4-weeks
Population: Participants in each arm with the total somatization score at 4-weeks.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Buspirone | 4-Week Change in Severity of Somatic Symptoms | -0.99 units on a scale | Standard Deviation 3.88 |
| Placebo | 4-Week Change in Severity of Somatic Symptoms | -2.00 units on a scale | Standard Deviation 3.93 |
Comparison: Adjusted mean difference from differences (DoD) from the baseline were computed using ANCOVA, regressing change from baseline to 4-weeks on treatment group and baseline value of the outcome. Wald 95% Confidence Intervals are reported; P value (2-sided) determined from a Wald Chi-Square test.p-value: 0.1995% CI: [-0.49, 2.51]ANCOVA
Secondary
4-Week Change in Stomach Fullness Symptom Severity
The outcome is assessed using self-reported assessment of stomach fullness severity in the prior 2-weeks using the Gastroparesis Cardinal Symptoms Index (GCSI) survey. The item is scored from 0 (no) to 5 (very severe) symptoms; the change is computed as the score at 4-weeks minus the baseline score.
Time frame: baseline and 4-weeks
Population: All participants assigned to the arm with 4-week visit data
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Buspirone | 4-Week Change in Stomach Fullness Symptom Severity | -1.16 score on a scale | Standard Deviation 1.55 |
| Placebo | 4-Week Change in Stomach Fullness Symptom Severity | -1.07 score on a scale | Standard Deviation 1.34 |
Comparison: The mean difference of differences (DoD) between Buspirone and Placebo, 95% confidence interval and P (2-sided) were derived from an ANCOVA, regressing an indicator for treatment group on fullness severity score, adjusting for the baseline value of fullness severity score.p-value: 0.7695% CI: [-0.69, 0.5]ANCOVA
Secondary
4-Week Change in Total Overall GCSI Symptom Severity
The outcome is assessed using the self-reported Gastroparesis Cardinal Symptom Index (GCSI) total score, which is computed as the average of the 3 subscores on the GCSI survey: 3-item early satiety/postprandial fullness subscore, the nausea/vomiting subscore (average of 3-items: nausea, retching, vomiting), and bloating subscore (average of 2-items: bloating, stomach visibly larger). Each item is scored from 0 (no) to 5 (very severe) symptoms in the past 2-weeks; the total score ranges from 0 to 5. The change is computed as the total score at 4-weeks minus the baseline total score. A negative change indicates improved symptoms.
Time frame: baseline and 4-weeks
Population: All patients with 4-week visit data for GCSI.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Buspirone | 4-Week Change in Total Overall GCSI Symptom Severity | -1.06 score on a scale | Standard Deviation 1.16 |
| Placebo | 4-Week Change in Total Overall GCSI Symptom Severity | -0.86 score on a scale | Standard Deviation 1 |
Comparison: Adjusted mean difference of differences (DoD) of change in outcome from baseline and 95% Confidence Intervals were computed using ANCOVA, regressing change from baseline to 4-weeks on treatment group and baseline value of the outcome. P (2-sided) were determined from a Wald Chi-Square test.p-value: 0.495% CI: [-0.66, 0.27]ANCOVA
Comparison: GCSI symptomatic improvement of 1+ points in total GCSI symptom score defined as change in GCSI total score at week 4 from baseline being a decrease of 1 or more points. This is a binary variable where 1=1+ reduction in change in GCSI total score, 0=change in GCSI total score from baseline at 4-weeks is \< 1.0.p-value: 0.5695% CI: [0.53, 3.21]Regression, Logistic
Secondary
4-Week Change in Upper Abdominal Pain and Discomfort Symptoms Severity
The outcome is assessed using the self-reported upper abdominal pain subscore, which is computed as the average of 2 scores for 2-items on the Patient Assessment of Upper Gastrointestinal Disorders-Symptom Severity Index (PAGI-SYM) survey: upper abdominal pain, upper abdominal discomfort. Each item is scored from 0 (no) to 5 (very severe) symptoms in the past 2-weeks; the subscore ranges from 0 to 5. The change is computed as the subscore at 4-weeks minus the baseline subscore.
Time frame: baseline and 4-weeks
Population: All participants assigned to the arm with a 4-week visit and values for the upper abdominal pain subscore.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Buspirone | 4-Week Change in Upper Abdominal Pain and Discomfort Symptoms Severity | -0.78 score on a scale | Standard Deviation 1.55 |
| Placebo | 4-Week Change in Upper Abdominal Pain and Discomfort Symptoms Severity | -0.95 score on a scale | Standard Deviation 1.63 |
Comparison: Adjusted mean difference of differences (DoD) from baseline were computed using ANCOVA, regressing change from baseline to 4-weeks on treatment group and baseline value of the outcome. Wald 95% Confidence Limits (CI) are reported; P (2-sided) determined from a Wald Chi-Square test.p-value: 0.5995% CI: [-0.44, 0.77]ANCOVA
Secondary
4-Week Change in Upper Abdominal Pain Symptom Severity
The outcome is assessed using self-reported assessment of upper abdominal pain severity in the prior 2-weeks using the Patient Assessment of Upper Gastrointestinal Disorders Symptom Severity Index (PAGI-SYM) survey. The item is scored from 0 (no) to 5 (very severe) symptoms; the change is computed as the score at 4-weeks minus the baseline score. A negative change indicates symptom improvement.
Time frame: baseline and 4-weeks
Population: All participants assigned to the arm with a 4-week visit and upper abdominal pain severity data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Buspirone | 4-Week Change in Upper Abdominal Pain Symptom Severity | -0.69 score on a scale | Standard Deviation 1.73 |
| Placebo | 4-Week Change in Upper Abdominal Pain Symptom Severity | -0.93 score on a scale | Standard Deviation 1.63 |
Comparison: Adjusted mean difference of differences (DoD) from baseline were computed using ANCOVA, regressing change from baseline to 4-weeks on treatment group and baseline value of the outcome. Wald 95% Confidence Limits (CI) are reported; P (2-sided) determined from a Wald Chi-Square test.p-value: 0.4695% CI: [-0.39, 0.88]ANCOVA
Secondary
4-Week Change in Vomiting Symptom Severity
The outcome is assessed using self-reported assessment of vomiting severity in the prior 2-weeks using the Gastroparesis Cardinal Symptom Index (GCSI) survey. The item is scored from 0 (no) to 5 (very severe) symptoms; the change is computed as the score at 4-weeks minus the baseline score. A negative change indicates improvement in vomiting severity.
Time frame: baseline and 4-weeks
Population: All participants assigned to the arm with a 4-week visit and data for vomiting severity.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Buspirone | 4-Week Change in Vomiting Symptom Severity | -0.71 score on a scale | Standard Deviation 1.81 |
| Placebo | 4-Week Change in Vomiting Symptom Severity | -0.57 score on a scale | Standard Deviation 1.47 |
Comparison: Adjusted mean difference of differences (DoD) from baseline were computed using ANCOVA, regressing change from baseline to 4-weeks on treatment group and baseline value of the outcome. Wald 95% Confidence Limits (CI) are reported; P (2-sided) determined from a Wald Chi-Square testp-value: 0.6595% CI: [-0.76, 0.47]ANCOVA
Secondary
4-Week Change Overall Quality of Health Due to Gastroparesis Issues
The outcome is assessed using the self-reported Patient Assessment of Upper Gastrointestinal Disorders-Quality of Life (PAGI-QOL) total score which comprises 30 items scored from 0 (none of the time) to 5 (all of the time) the participant's QOL has been affected by their gastrointestinal issues in the prior two weeks. The total score is the mean of the 5 subscale scores and ranges from 0 (lowest QOL) to 5 (highest QOL) in past 2-weeks. The change is computed as the score at 4-weeks minus the baseline score. A positive change indicates improved QOL.
Time frame: baseline and 4-weeks
Population: Participants with available PAGI-QOL data at 4-weeks. 1 Placebo patient did not have values for PAGI-QOL total score.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Buspirone | 4-Week Change Overall Quality of Health Due to Gastroparesis Issues | 0.43 score on a scale | Standard Deviation 0.81 |
| Placebo | 4-Week Change Overall Quality of Health Due to Gastroparesis Issues | 0.64 score on a scale | Standard Deviation 0.95 |
Comparison: Adjusted mean difference of differences (DoD) from baseline were computed using ANCOVA, regressing change from baseline to 4-weeks on treatment group and baseline value of PAGI-QOL total score.p-value: 0.2595% CI: [-0.57, 0.15]ANCOVA
Secondary
Change at 4-weeks in the Intragastric Meal Distribution (IMD)
The Intragastric meal distribution (IMD) is assessed at baseline and 4-weeks during the Gastric Emptying Scintigraphy Test. The ratio of gastric counts of the meal in the proximal stomach to the distal stomach is used to compute the Intragastric meal distribution (IMD) which can be used as an indirect measure of Fundic Accommodation.
Time frame: baseline and 4-weeks
Population: Patients in each treatment arm with measurements for IMD at 4-weeks.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Buspirone | Change at 4-weeks in the Intragastric Meal Distribution (IMD) | -0.04 ratio | Standard Deviation 0.13 |
| Placebo | Change at 4-weeks in the Intragastric Meal Distribution (IMD) | 0.02 ratio | Standard Deviation 0.13 |
Comparison: Adjusted mean difference of differences (DoD) were computed using ANCOVA, regressing change in IMD from baseline to 4-weeks on treatment group and the baseline value of IMD. Wald 95% Confidence Intervals are reported; P (2-sided) determined from a Wald Chi-Square test.p-value: 0.195% CI: [-0.12, 0.01]ANCOVA
Secondary
Change From Baseline at 4-weeks in the Water Load Satiety Test (WLST)
The Water Load Satiety Test (WLST) is the amount of water a patient can consume until full in 5 minutes. The volume of water is recorded. The change is computed as the volume of water ingested at baseline subtracted from the amount of water ingested at 4-weeks. A positive change indicates that the patient can ingest more water at 4-weeks than at baseline.
Time frame: baseline and 4-weeks
Population: Participants in each treatment arm with a volume of water measured at both baseline and 4-weeks.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Buspirone | Change From Baseline at 4-weeks in the Water Load Satiety Test (WLST) | -43.3 ml | Standard Error 219.1 |
| Placebo | Change From Baseline at 4-weeks in the Water Load Satiety Test (WLST) | -21.8 ml | Standard Error 145.6 |
Comparison: Adjusted mean difference of differences (DoD) from baseline were computed using ANCOVA, regressing change from baseline to 4-weeks on treatment group and baseline value of teh outcome. Wald 95% Confidence Limits are reported; P (2-sided) determined from a Wald Chi-Square test.p-value: 0.2995% CI: [-99.4, 56.4]ANCOVA
Other Pre-specified
4-Week Cardiac Rhythm
This safety outcome is computed from the results of an electrocardiogram (ECG) QTc interval at 4-weeks measured in milliseconds (msec).
Time frame: baseline and 4-weeks
Population: All participants assigned to the arm with 4-week visit data for the Electrocardiogram QTc interval.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Buspirone | 4-Week Cardiac Rhythm | -2.80 milliseconds (msec) | Standard Deviation 19.18 |
| Placebo | 4-Week Cardiac Rhythm | 3.63 milliseconds (msec) | Standard Deviation 23.42 |
Comparison: Adjusted mean difference of differences (DoD) from baseline were computed using ANCOVA, regressing change from baseline to 4-weeks on treatment group and baseline value of the outcome. Wald 95% Confidence Limits (CI) are reported; P (2-sided) determined from a Wald Chi-Square test.p-value: 0.2795% CI: [-17.9, 5.03]ANCOVA
Other Pre-specified
4-Week Change in Aspartate Aminotransferase (ALT)
This safety outcome is computed by subtracting the baseline level of Alanine Aminotransferase (ALT) (U/L) from the 4-week level.
Time frame: baseline and 4-weeks
Population: All participants assigned to the arm with a 4-week visit and a measurement for ALT.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Buspirone | 4-Week Change in Aspartate Aminotransferase (ALT) | 0.32 U/L | Standard Deviation 15.93 |
| Placebo | 4-Week Change in Aspartate Aminotransferase (ALT) | 1.34 U/L | Standard Deviation 9.57 |
Comparison: Adjusted mean difference of differences (DoD) from baseline were computed using ANCOVA, regressing change from baseline to 4-weeks on treatment group and baseline value of the outcome. Wald 95% Confidence Intervals are reported; P (2-sided) determined from a Wald Chi-Square test.p-value: 0.7495% CI: [-6.93, 4.89]ANCOVA
Other Pre-specified
4-Week Change in Creatinine
This safety outcome is computed by subtracting the baseline level of creatinine (mg/dL) from the 4-week level.
Time frame: baseline and 4-weeks
Population: All participants assigned to the arm with a 4-week visit and a measurement for Creatinine.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Buspirone | 4-Week Change in Creatinine | 0.02 mg/dL | Standard Deviation 0.07 |
| Placebo | 4-Week Change in Creatinine | -0.01 mg/dL | Standard Deviation 0.11 |
Comparison: Adjusted mean difference of differences (DoD) from baseline were computed using ANCOVA, regressing change from baseline to 4-weeks on treatment group and baseline value of the outcome. 95% Wald Confidence Intervals are reported; P (2-sided) determined from a Wald Chi-Square test.p-value: 0.1895% CI: [-0.01, 0.08]ANCOVA
Other Pre-specified
4-Week Change in Fasting Glucose
This safety outcome is computed by subtracting the baseline level of glucose (mg/dL) from the 4-week level.
Time frame: baseline and 4-weeks
Population: All participants assigned to the arm with a 4-week visit with a measurement for glucose.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Buspirone | 4-Week Change in Fasting Glucose | 10.30 mg/dL | Standard Deviation 38.1 |
| Placebo | 4-Week Change in Fasting Glucose | 10.69 mg/dL | Standard Deviation 42.21 |
Comparison: Adjusted mean difference of differences (DoD) from baseline were computed using ANCOVA, regressing change from baseline to 4-weeks on treatment group and baseline value of the outcome. 95% Wald Confidence Intervals are reported; P (2-sided) determined from a Wald Chi-Square test.p-value: 0.9795% CI: [-20.42, 19.64]ANCOVA
Other Pre-specified
4-Week Change in Weight
This safety outcome is computed by subtracting the weight (kg) at baseline from the weight (kg) at 4-weeks
Time frame: baseline and 4-weeks
Population: All participants assigned to the arm with a 4-week visit and a measurement for weight.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Buspirone | 4-Week Change in Weight | -0.34 kilogram | Standard Deviation 1.36 |
| Placebo | 4-Week Change in Weight | -0.43 kilogram | Standard Deviation 1.99 |
Comparison: Adjusted mean difference of differences (DoD) from baseline were computed using ANCOVA, regressing change from baseline to week 4 on treatment group and baseline value of the outcome. Wald 95% Confidence Limits (CI) are reported: P (2-sided) determined from Wald Chi-Square test.p-value: 0.8495% CI: [-0.78, 0.95]ANCOVA
Other Pre-specified
Adverse Events by Body Classification System by Treatment Group During the Trial
Adverse events were reported on the Adverse Event Report form by the principal investigator at each clinic site using the CTCAE v5 classification system.
Time frame: over 4-weeks of treatment
Population: All patients randomized into each treatment group.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Buspirone | Adverse Events by Body Classification System by Treatment Group During the Trial | Immune system | 1 events by body classification |
| Buspirone | Adverse Events by Body Classification System by Treatment Group During the Trial | Infections & infestations | 3 events by body classification |
| Buspirone | Adverse Events by Body Classification System by Treatment Group During the Trial | Total | 12 events by body classification |
| Buspirone | Adverse Events by Body Classification System by Treatment Group During the Trial | Gastrointestinal | 3 events by body classification |
| Buspirone | Adverse Events by Body Classification System by Treatment Group During the Trial | Investigations | 0 events by body classification |
| Buspirone | Adverse Events by Body Classification System by Treatment Group During the Trial | Metabolic & nutrition | 1 events by body classification |
| Buspirone | Adverse Events by Body Classification System by Treatment Group During the Trial | Nervous system | 3 events by body classification |
| Buspirone | Adverse Events by Body Classification System by Treatment Group During the Trial | Renal & urinary | 1 events by body classification |
| Buspirone | Adverse Events by Body Classification System by Treatment Group During the Trial | Surgical & medical | 0 events by body classification |
| Buspirone | Adverse Events by Body Classification System by Treatment Group During the Trial | Musculoskeletal & connective tissue disorders | 0 events by body classification |
| Placebo | Adverse Events by Body Classification System by Treatment Group During the Trial | Renal & urinary | 1 events by body classification |
| Placebo | Adverse Events by Body Classification System by Treatment Group During the Trial | Immune system | 0 events by body classification |
| Placebo | Adverse Events by Body Classification System by Treatment Group During the Trial | Metabolic & nutrition | 0 events by body classification |
| Placebo | Adverse Events by Body Classification System by Treatment Group During the Trial | Musculoskeletal & connective tissue disorders | 1 events by body classification |
| Placebo | Adverse Events by Body Classification System by Treatment Group During the Trial | Total | 9 events by body classification |
| Placebo | Adverse Events by Body Classification System by Treatment Group During the Trial | Nervous system | 0 events by body classification |
| Placebo | Adverse Events by Body Classification System by Treatment Group During the Trial | Gastrointestinal | 3 events by body classification |
| Placebo | Adverse Events by Body Classification System by Treatment Group During the Trial | Infections & infestations | 1 events by body classification |
| Placebo | Adverse Events by Body Classification System by Treatment Group During the Trial | Surgical & medical | 1 events by body classification |
| Placebo | Adverse Events by Body Classification System by Treatment Group During the Trial | Investigations | 2 events by body classification |
p-value: 0.52Binomial probability test
Other Pre-specified
Assessment of Adverse Events Over 4-Weeks
This safety outcome is the frequency over the 4-weeks of the study of all reported adverse events using the v5.0 CTCAE classification system.
Time frame: over 4-weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Buspirone | Assessment of Adverse Events Over 4-Weeks | 12 events |
| Placebo | Assessment of Adverse Events Over 4-Weeks | 8 events |
Comparison: Event rates are computed by treatment arm by dividing the total adverse events over 4-weeks by the number of patient-months of follow-up to 4-weeks. Event rates are compared by treatment arm using an exact poisson regression for event rates.p-value: 0.6495% CI: [0.57, 2.82]Exact poisson regression
Other Pre-specified
Assessment of the Severity of Adverse Events Over 4-Weeks
This safety outcome is the frequency over the 4-weeks of the study of all reported adverse events' severity grade as classified by the NCI's Common Terminology Criteria for Adverse Events (CTCAE v5.0). For the patient with 2 AE's, the AE with the maximum severity is reported.
Time frame: over 4-weeks
Population: All participants randomized in the trial with events occurring over the 4 weeks of follow-up.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Buspirone | Assessment of the Severity of Adverse Events Over 4-Weeks | 2-moderate severity | 6 Participants |
| Buspirone | Assessment of the Severity of Adverse Events Over 4-Weeks | 3-severe | 1 Participants |
| Buspirone | Assessment of the Severity of Adverse Events Over 4-Weeks | No Adverse events | 35 Participants |
| Buspirone | Assessment of the Severity of Adverse Events Over 4-Weeks | 1-mild severity | 5 Participants |
| Buspirone | Assessment of the Severity of Adverse Events Over 4-Weeks | 4-life threatening | 0 Participants |
| Buspirone | Assessment of the Severity of Adverse Events Over 4-Weeks | 5-death | 0 Participants |
| Placebo | Assessment of the Severity of Adverse Events Over 4-Weeks | 4-life threatening | 0 Participants |
| Placebo | Assessment of the Severity of Adverse Events Over 4-Weeks | 2-moderate severity | 6 Participants |
| Placebo | Assessment of the Severity of Adverse Events Over 4-Weeks | 1-mild severity | 2 Participants |
| Placebo | Assessment of the Severity of Adverse Events Over 4-Weeks | 3-severe | 0 Participants |
| Placebo | Assessment of the Severity of Adverse Events Over 4-Weeks | 5-death | 0 Participants |
| Placebo | Assessment of the Severity of Adverse Events Over 4-Weeks | No Adverse events | 41 Participants |
Comparison: A Fisher's Exact test was used for comparisons of events by treatment by severity grade. One patient in the Buspirone arm had 2 AEs during the trial; for analysis by severity grade the maximum severity grade was used.p-value: 0.5495% CI: [0.35, 2.62]Fisher Exact
Other Pre-specified
Serious Adverse Events
Serious Adverse Event (SAE) defined by the FDA as an event meeting one or more of the following criteria; inpatient hospitalization or prolonged existing hospitalization; persistent or significant incapacity or substantial disruption of ability to conduct normal life functions; jeopardized patient and required medical or surgical intervention to prevent a serious event; or congenital anomaly or birth defect.
Time frame: over 4 weeks of treatment
Population: All patients randomized into each treatment arm
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Buspirone | Serious Adverse Events | 1 Serious adverse events |
| Placebo | Serious Adverse Events | 1 Serious adverse events |
p-value: 1Fisher Exact
Other Pre-specified
Total Number of Hospitalizations Over 4-weeks of Treatment
Hospitalization events by treatment arm were reported on the Adverse Event Case-Report form at each visit and also at time of occurrence and tabulated at end of treatment visit for comparison between placebo and buspirone arms.
Time frame: over the 4-weeks of the trial
Population: all participants by treatment arm randomized into the trial
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Buspirone | Total Number of Hospitalizations Over 4-weeks of Treatment | 1 hospitalizations |
| Placebo | Total Number of Hospitalizations Over 4-weeks of Treatment | 0 hospitalizations |
Comparison: Event rates were computed by dividing the number of hospitalizations over 4-weeks by the number of person-years. An exact poisson regression was used to compare events by treatment group.p-value: 195% CI: [0, 40.36]Exact poisson regression