Cyclic Vomiting Syndrome
Conditions
Keywords
Cyclic Vomiting Syndrome, CVS, Vomiting, Retching, Abdominal migraine, Nausea, Stomach pain, Unexplained vomiting, Functional GI Disorder, CVSHOPE.com, Throwing up, Puking, Dry heaving, Food poisoning, Episodes, Repeated food poisoning
Brief summary
This is a multicenter, randomized, double-blind, parallel group, placebo-controlled, efficacy and safety study of adult outpatients diagnosed with CVS and experiencing recurring episodes of stereotypical vomiting.
Detailed description
A Randomized, Double-Blind, Placebo Controlled Study to Evaluate the Safety and Efficacy of Staccato Granisetron (AZ-010) for the Acute Treatment of Moderate to Severe Cyclic Vomiting Syndrome
Interventions
COMBINATION_PRODUCTStaccato Placebo
Subject who received a single inhaled dose (Staccato Placebo)
COMBINATION_PRODUCT3mg AZ-010
Subjects who received a single inhaled dose (3mg)
COMBINATION_PRODUCT1mg AZ010
Subjects who received a single inhaled dose (1mg)
Sponsors
Alexza Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
Double Blind
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* Adult males and females between 18 and 60 years of age, inclusive at the time of signing the informed consent document. * Diagnosis of cyclic vomiting syndrome (CVS) using the Rome IV diagnostic criteria. * Otherwise healthy, as determined by the responsible physician, based on a medical evaluation including history, physical examination, vital signs, electrocardiograms (ECGs) and laboratory tests assessed at the screening visit * Negative urine tests for selected drugs of abuse and alcohol breath test at Screening.
Exclusion criteria
* Any significant medical or psychiatric condition that could, in the Investigator's opinion, compromise the subject's safety or interfere with the completion of this protocol. * Any condition, including the presence of laboratory abnormalities or pulmonary condition, which according to the Investigator places the subject at unacceptable risk if he/she were to participate in the study. * A diagnosis of any gastrointestinal disorder other than CVS that in the judgement of the Investigator could compromise the subject's safety or interfere with the interpretation of safety or efficacy data.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Vomiting/Retching Events Reported by Study Participants Following Treatment/Dosing During the Home Treament Period. | Within the following timepoints: 30, 60, 90 and 120-minutes post-dose. | The primary efficacy endpoint for this study was the number vomiting/retching events in the two hours following initial treatment. Patients recorded the number of vomiting and retching events that they experienced which occurred 2 hours post dose. Observations occurred at 4 time points: 30 minutes post-dose, 1 hour post-dose, 90 minutes post-dose, and 2 hours post-dose. While each treatment group contained 47-49 patients, only 22-35 patients per treatment group (\ 45-70%) recorded vomiting/retching events at any given time point. Safety and tolerability of AZ-010 was assessed by evaluating adverse events, vital signs, 12-lead ECG, clinical laboratory results, and physical examination. Clinically significant deteriorations in physical examination findings (in the opinion of the investigator) are captured and summarized as adverse events. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Prior Episode Questionnaire | 24 hours after each dose | The duration of the CVS episode at 24 hours in relation to their typical CVS episodes (Prior Episode Questionnaire) and the intensity of the CVS episode at 24 hours in relation to their typical CVS episodes. A 3-point scale was used. The questions were prompted approximately 24 hours after each dose of study medication was administered. Duration: (Score definition: 1 = shorter duration than typical previous episode; 2 = same duration as typical previous episode; 3 = longer duration than typical previous episode) Intensity: (Score definition: 1 = less intense than typical previous episode; 2 = same intensity as typical previous episode; 3 = more intense than typical previous episode) |
| Rescue Medication Use Within 1 Day of Dose | 24 hours post dose | The percentage of patients who used rescue medication within the first day of treatment; patients confirming the individual had used some sort of rescue medication. |
| Health Care Provider Visits; Visit to Urgent Care, Emergency Department, or Physician's Office | Within Day 1 after dosing | Health Care Provider Visits; Visit to Urgent Care, Emergency Department, or Physician's Office for care within the first day following dosing for a CVS episode. |
| Anxiety/Panic Visual Analog Scale (VAS) Score | 24 hours after treatment dose | Assessment of anxiety/panic at 2, 6, 12, and 24 hours following treatment. The assessment of anxiety/panic Visual Analog Scale (VAS) score whereby 0 = no anxiety/panic and 100 = worst possible anxiety/panic 0-100; 0 = no anxiety/panic and 100 = worst possible anxiety/panic). Participants were asked to rate their anxiety/panic on scale of 0-100 at each time point. The higher the number, the more intense the symptom. |
| Abdominal Pain, Visual Analog Scale (VAS) Score | Up to 24 hours post dose. | The patient was asked the abdominal pain in relation to their last vomiting/retching episode, whereby 0 = no pain and 100 = worst possible pain at timepoints 2, 6, 12 and 24 hours post-dose |
| Intensity of Vomiting/Retching Attack | Within 24 hours post dose. | The Intensity of Attack scale assessed the severity of the last vomiting/retching episode at 2, 6, 12, and 24 hours post dose. Intensity of attack is evaluated on a scale of 1-4 (1=Mild, 2=Moderate, 3=Severe, 4=Excruciating). |
| Rhodes Index of Nausea, Vomiting, and Retching (RINVR) | Within 24 hours following treatment. | The Rhodes Index of nausea, vomiting, and retching (RINVR) at 6, 12, and 24 hours following treatment. The Rhodes Index of nausea, vomiting, and retching (RINVR) is designed to assess the degree of nausea distress and vomiting distress in patients. It is composed of 8 questions, and each question has 5 choices. The 5 choices for each individual question are scores from 0 to 4, with 0 being the lowest level without any symptoms related to nausea/vomiting/retching and 4 being the highest level. Individual question scores can be tracked over time, or a composite score with a total scoring range of 0 to 32 can be formed by adding the individual scores of the symptom occurrence and degree of discomfort questions together. Composite scores classified as follows: 0: no symptoms, 1-8: mild, 9-16: moderate, 17-24: great, 25-32: severe. This scale was adapted for the ePD, and patients were prompted to answer the questions according to the Schedule of Events. |
Countries
United States
Participant flow
Recruitment details
This study was a multicenter study conducted at 18 sites in the United States. Of these, only 17 sites were activated, and only 15 sites enrolled subjects. Study Period: 1 year 5 months Study Start: 05 February 2021 Study End: 26 July 2022 50 patients randomized to each of 3 treatment groups: 1 mg AZ-010, 3 mg AZ-010, or matching Staccato® Placebo Patients were screened at the Research Clinic to determine eligibility for study participation no more than14 days prior to Visit 2.
Pre-assignment details
Participant eligibility inclusion and exclusion criteria via the following assessments: Medical history (with particular reference to history of vomiting symptoms, CVS diagnosis, typical duration of CVS episode, average # of vomiting/retching events in typical CVS episode, frequency of CVS episodes per year, any triggers for CVS episode, conditions that may cause similar symptoms, treatment history, and current medications, medical history, COVID-19 screening.
Participants by arm
| Arm | Count |
|---|---|
| 1mg AZ010 Single orally-inhaled dose
1mg AZ010: Subject will receive a single inhaled dose (1mg) | 50 |
| 3mg AZ010 Single orally-inhaled dose
3mg AZ-010: Subject will receive a single inhaled dose (3mg) | 51 |
| Placebo Single orally-inhaled dose
Staccato Placebo: Subject will receive a single inhaled dose (Staccato Placebo) | 49 |
| Total | 150 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Discontinued Prior to Dosing | 0 | 0 | 2 |
| Overall Study | Lost to Follow-up | 2 | 1 | 1 |
| Overall Study | Physician Decision | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Total | 1mg AZ010 | Placebo | 3mg AZ010 |
|---|---|---|---|---|
| Age, Continuous | 35.2 years STANDARD_DEVIATION 11.53 | 33.5 years STANDARD_DEVIATION 11.95 | 36.2 years STANDARD_DEVIATION 10.22 | 36.0 years STANDARD_DEVIATION 12.3 |
| Body Mass Index (kg/m2) | 28.244 kg/m^2 STANDARD_DEVIATION 7.2635 | 28.979 kg/m^2 STANDARD_DEVIATION 7.7236 | 28.238 kg/m^2 STANDARD_DEVIATION 7.9544 | 27.529 kg/m^2 STANDARD_DEVIATION 6.0793 |
| Childbearing potential (No) | 70 Participants | 26 Participants | 22 Participants | 22 Participants |
| Childbearing potential (Yes) | 80 Participants | 24 Participants | 27 Participants | 29 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 18 Participants | 8 Participants | 5 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 127 Participants | 41 Participants | 41 Participants | 45 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 5 Participants | 1 Participants | 3 Participants | 1 Participants |
| Height | 168.79 cm STANDARD_DEVIATION 8.919 | 168.85 cm STANDARD_DEVIATION 9.166 | 168.81 cm STANDARD_DEVIATION 7.91 | 168.73 cm STANDARD_DEVIATION 9.729 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 1 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 14 Participants | 7 Participants | 3 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 130 Participants | 41 Participants | 44 Participants | 45 Participants |
| Sex: Female, Male Female | 104 Participants | 34 Participants | 36 Participants | 34 Participants |
| Sex: Female, Male Male | 46 Participants | 16 Participants | 13 Participants | 17 Participants |
| Weight | 81.38 kg STANDARD_DEVIATION 23.655 | 83.28 kg STANDARD_DEVIATION 24.854 | 82.08 kg STANDARD_DEVIATION 26.443 | 78.85 kg STANDARD_DEVIATION 19.5 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 50 | 0 / 51 | 0 / 49 |
| other Total, other adverse events | 28 / 50 | 40 / 51 | 44 / 49 |
| serious Total, serious adverse events | 3 / 50 | 3 / 51 | 3 / 49 |
Outcome results
Primary
The Number of Vomiting/Retching Events Reported by Study Participants Following Treatment/Dosing During the Home Treament Period.
The primary efficacy endpoint for this study was the number vomiting/retching events in the two hours following initial treatment. Patients recorded the number of vomiting and retching events that they experienced which occurred 2 hours post dose. Observations occurred at 4 time points: 30 minutes post-dose, 1 hour post-dose, 90 minutes post-dose, and 2 hours post-dose. While each treatment group contained 47-49 patients, only 22-35 patients per treatment group (\ 45-70%) recorded vomiting/retching events at any given time point. Safety and tolerability of AZ-010 was assessed by evaluating adverse events, vital signs, 12-lead ECG, clinical laboratory results, and physical examination. Clinically significant deteriorations in physical examination findings (in the opinion of the investigator) are captured and summarized as adverse events.
Time frame: Within the following timepoints: 30, 60, 90 and 120-minutes post-dose.
Population: Per protocol population (CVS patients between 18 and 60 years of age who experienced at least 3 episodes of recurrent vomiting in the last 12 months and 2 episodes in the last 6 months.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1mg AZ010 | The Number of Vomiting/Retching Events Reported by Study Participants Following Treatment/Dosing During the Home Treament Period. | Number Vomiting & Retching Events, First Available Efficacy Data, 30 minutes post dose | 0.69 event | Standard Deviation 1.168 |
| 1mg AZ010 | The Number of Vomiting/Retching Events Reported by Study Participants Following Treatment/Dosing During the Home Treament Period. | Number Vomiting & Retching Events First Available Efficacy Data, 1 hour post dose | 1.48 event | Standard Deviation 2.694 |
| 1mg AZ010 | The Number of Vomiting/Retching Events Reported by Study Participants Following Treatment/Dosing During the Home Treament Period. | Number Vomiting & Retching Events First Available Efficacy Data, 90 minutes post dose | 2.17 event | Standard Deviation 4.243 |
| 1mg AZ010 | The Number of Vomiting/Retching Events Reported by Study Participants Following Treatment/Dosing During the Home Treament Period. | Number Vomiting & Retching Events First Available Efficacy Data, 2 hours post dose | 3.10 event | Standard Deviation 5.576 |
| 3mg AZ010 | The Number of Vomiting/Retching Events Reported by Study Participants Following Treatment/Dosing During the Home Treament Period. | Number Vomiting & Retching Events First Available Efficacy Data, 2 hours post dose | 4.21 event | Standard Deviation 5.279 |
| 3mg AZ010 | The Number of Vomiting/Retching Events Reported by Study Participants Following Treatment/Dosing During the Home Treament Period. | Number Vomiting & Retching Events, First Available Efficacy Data, 30 minutes post dose | 1.43 event | Standard Deviation 1.975 |
| 3mg AZ010 | The Number of Vomiting/Retching Events Reported by Study Participants Following Treatment/Dosing During the Home Treament Period. | Number Vomiting & Retching Events First Available Efficacy Data, 90 minutes post dose | 3.32 event | Standard Deviation 3.906 |
| 3mg AZ010 | The Number of Vomiting/Retching Events Reported by Study Participants Following Treatment/Dosing During the Home Treament Period. | Number Vomiting & Retching Events First Available Efficacy Data, 1 hour post dose | 2.43 event | Standard Deviation 3.099 |
| Placebo | The Number of Vomiting/Retching Events Reported by Study Participants Following Treatment/Dosing During the Home Treament Period. | Number Vomiting & Retching Events First Available Efficacy Data, 2 hours post dose | 2.61 event | Standard Deviation 4.408 |
| Placebo | The Number of Vomiting/Retching Events Reported by Study Participants Following Treatment/Dosing During the Home Treament Period. | Number Vomiting & Retching Events First Available Efficacy Data, 1 hour post dose | 2.13 event | Standard Deviation 3.18 |
| Placebo | The Number of Vomiting/Retching Events Reported by Study Participants Following Treatment/Dosing During the Home Treament Period. | Number Vomiting & Retching Events First Available Efficacy Data, 90 minutes post dose | 2.59 event | Standard Deviation 4.205 |
| Placebo | The Number of Vomiting/Retching Events Reported by Study Participants Following Treatment/Dosing During the Home Treament Period. | Number Vomiting & Retching Events, First Available Efficacy Data, 30 minutes post dose | 1.33 event | Standard Deviation 2.239 |
Comparison: Null hypothesis is there was no difference between groups treated with AZ-010 (1 mg or 3 mg) and the placebo group in the mean number of vomiting/retching events in the 2 hours following. treatment. Baseline, body weight, height, body mass index, age as covariates, and the treatment group and study site as factors. All statistical tests were 2-sided with a significance value of ≤ 0.05.p-value: 0.7024ANOVA
p-value: 0.2051ANOVA
Secondary
Abdominal Pain, Visual Analog Scale (VAS) Score
The patient was asked the abdominal pain in relation to their last vomiting/retching episode, whereby 0 = no pain and 100 = worst possible pain at timepoints 2, 6, 12 and 24 hours post-dose
Time frame: Up to 24 hours post dose.
Population: Per protocol population (CVS patients between 18 and 60 years of age who experienced at least 3 episodes of recurrent vomiting in the last 12 months and 2 episodes in the last 6 months.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1mg AZ010 | Abdominal Pain, Visual Analog Scale (VAS) Score | Abdominal Pain VAS Score,2 hour, post-dose | 45.48 units on a scale | Standard Deviation 27.318 |
| 1mg AZ010 | Abdominal Pain, Visual Analog Scale (VAS) Score | Abdominal Pain VAS Score,6 hour, post-dose | 51.50 units on a scale | Standard Deviation 17.849 |
| 1mg AZ010 | Abdominal Pain, Visual Analog Scale (VAS) Score | Abdominal Pain VAS Score,12 hour, post-dose | 36.67 units on a scale | Standard Deviation 7.024 |
| 1mg AZ010 | Abdominal Pain, Visual Analog Scale (VAS) Score | Abdominal Pain VAS Score, 24 hour, post-dose | 32.60 units on a scale | Standard Deviation 17.771 |
| 3mg AZ010 | Abdominal Pain, Visual Analog Scale (VAS) Score | Abdominal Pain VAS Score, 24 hour, post-dose | 43.88 units on a scale | Standard Deviation 38.264 |
| 3mg AZ010 | Abdominal Pain, Visual Analog Scale (VAS) Score | Abdominal Pain VAS Score,2 hour, post-dose | 53.04 units on a scale | Standard Deviation 32.227 |
| 3mg AZ010 | Abdominal Pain, Visual Analog Scale (VAS) Score | Abdominal Pain VAS Score,12 hour, post-dose | 51.38 units on a scale | Standard Deviation 33.393 |
| 3mg AZ010 | Abdominal Pain, Visual Analog Scale (VAS) Score | Abdominal Pain VAS Score,6 hour, post-dose | 47.25 units on a scale | Standard Deviation 33.97 |
| Placebo | Abdominal Pain, Visual Analog Scale (VAS) Score | Abdominal Pain VAS Score, 24 hour, post-dose | 66.25 units on a scale | Standard Deviation 11.354 |
| Placebo | Abdominal Pain, Visual Analog Scale (VAS) Score | Abdominal Pain VAS Score,6 hour, post-dose | 32.57 units on a scale | Standard Deviation 22.846 |
| Placebo | Abdominal Pain, Visual Analog Scale (VAS) Score | Abdominal Pain VAS Score,12 hour, post-dose | 61.25 units on a scale | Standard Deviation 30.489 |
| Placebo | Abdominal Pain, Visual Analog Scale (VAS) Score | Abdominal Pain VAS Score,2 hour, post-dose | 51.60 units on a scale | Standard Deviation 29.39 |
Comparison: Participants were asked to rate their abdominal pain, nausea, and anxiety/panic on scale of 0-100 at each time point. The higher the number, the more intense the symptom.p-value: 0.0504Mixed Models Analysis
p-value: 0.8246Mixed Models Analysis
Secondary
Anxiety/Panic Visual Analog Scale (VAS) Score
Assessment of anxiety/panic at 2, 6, 12, and 24 hours following treatment. The assessment of anxiety/panic Visual Analog Scale (VAS) score whereby 0 = no anxiety/panic and 100 = worst possible anxiety/panic 0-100; 0 = no anxiety/panic and 100 = worst possible anxiety/panic). Participants were asked to rate their anxiety/panic on scale of 0-100 at each time point. The higher the number, the more intense the symptom.
Time frame: 24 hours after treatment dose
Population: Per protocol population (CVS patients between 18 and 60 years of age who experienced at least 3 episodes of recurrent vomiting in the last 12 months and 2 episodes in the last 6 months.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1mg AZ010 | Anxiety/Panic Visual Analog Scale (VAS) Score | Anxiety/Panic VAS Score, 2 hour, post-dose | 51.30 score on a scale | Standard Deviation 34.907 |
| 1mg AZ010 | Anxiety/Panic Visual Analog Scale (VAS) Score | Anxiety/Panic VAS Score, 6 hour, post-dose | 48.25 score on a scale | Standard Deviation 17.343 |
| 1mg AZ010 | Anxiety/Panic Visual Analog Scale (VAS) Score | Anxiety/Panic VAS Score, 12 hour, post-dose | 31.00 score on a scale | Standard Deviation 28.827 |
| 1mg AZ010 | Anxiety/Panic Visual Analog Scale (VAS) Score | Anxiety/Panic VAS Score, 24 hour, post-dose | 18.00 score on a scale | Standard Deviation 19.378 |
| 3mg AZ010 | Anxiety/Panic Visual Analog Scale (VAS) Score | Anxiety/Panic VAS Score, 24 hour, post-dose | 37.88 score on a scale | Standard Deviation 31.439 |
| 3mg AZ010 | Anxiety/Panic Visual Analog Scale (VAS) Score | Anxiety/Panic VAS Score, 2 hour, post-dose | 52.08 score on a scale | Standard Deviation 35.02 |
| 3mg AZ010 | Anxiety/Panic Visual Analog Scale (VAS) Score | Anxiety/Panic VAS Score, 12 hour, post-dose | 51.15 score on a scale | Standard Deviation 31.947 |
| 3mg AZ010 | Anxiety/Panic Visual Analog Scale (VAS) Score | Anxiety/Panic VAS Score, 6 hour, post-dose | 64.00 score on a scale | Standard Deviation 35.071 |
| Placebo | Anxiety/Panic Visual Analog Scale (VAS) Score | Anxiety/Panic VAS Score, 24 hour, post-dose | 62.25 score on a scale | Standard Deviation 30.478 |
| Placebo | Anxiety/Panic Visual Analog Scale (VAS) Score | Anxiety/Panic VAS Score, 6 hour, post-dose | 51.29 score on a scale | Standard Deviation 20.605 |
| Placebo | Anxiety/Panic Visual Analog Scale (VAS) Score | Anxiety/Panic VAS Score, 12 hour, post-dose | 64.00 score on a scale | Standard Deviation 26.533 |
| Placebo | Anxiety/Panic Visual Analog Scale (VAS) Score | Anxiety/Panic VAS Score, 2 hour, post-dose | 47.72 score on a scale | Standard Deviation 32.849 |
Comparison: Participants were asked to rate their anxiety/panic on scale of 0-100 at each time point. The higher the number, the more intense the symptom.p-value: 0.0504Mixed Models Analysis
p-value: 0.8246Mixed Models Analysis
Secondary
Health Care Provider Visits; Visit to Urgent Care, Emergency Department, or Physician's Office
Health Care Provider Visits; Visit to Urgent Care, Emergency Department, or Physician's Office for care within the first day following dosing for a CVS episode.
Time frame: Within Day 1 after dosing
Population: Per protocol population (CVS patients between 18 and 60 years of age who experienced at least 3 episodes of recurrent vomiting in the last 12 months and 2 episodes in the last 6 months.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 1mg AZ010 | Health Care Provider Visits; Visit to Urgent Care, Emergency Department, or Physician's Office | Patients requiring healthcare provider visit within 24 hours post dose of CVS episode. | 2 Participants |
| 1mg AZ010 | Health Care Provider Visits; Visit to Urgent Care, Emergency Department, or Physician's Office | Patients not requiring healthcare provider visit within 24 hours post dose of CVS episode. | 45 Participants |
| 3mg AZ010 | Health Care Provider Visits; Visit to Urgent Care, Emergency Department, or Physician's Office | Patients requiring healthcare provider visit within 24 hours post dose of CVS episode. | 0 Participants |
| 3mg AZ010 | Health Care Provider Visits; Visit to Urgent Care, Emergency Department, or Physician's Office | Patients not requiring healthcare provider visit within 24 hours post dose of CVS episode. | 49 Participants |
| Placebo | Health Care Provider Visits; Visit to Urgent Care, Emergency Department, or Physician's Office | Patients requiring healthcare provider visit within 24 hours post dose of CVS episode. | 0 Participants |
| Placebo | Health Care Provider Visits; Visit to Urgent Care, Emergency Department, or Physician's Office | Patients not requiring healthcare provider visit within 24 hours post dose of CVS episode. | 44 Participants |
p-value: 0.9732Mantel Haenszel
p-value: 0.1471Mantel Haenszel
Secondary
Intensity of Vomiting/Retching Attack
The Intensity of Attack scale assessed the severity of the last vomiting/retching episode at 2, 6, 12, and 24 hours post dose. Intensity of attack is evaluated on a scale of 1-4 (1=Mild, 2=Moderate, 3=Severe, 4=Excruciating).
Time frame: Within 24 hours post dose.
Population: Per protocol population (CVS patients between 18 and 60 years of age who reported intensity of vomiting attack.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1mg AZ010 | Intensity of Vomiting/Retching Attack | Intensity of Attack Scale (Efficacy Population) 2 hours post-dose | 2.29 units on a scale | Standard Deviation 0.488 |
| 1mg AZ010 | Intensity of Vomiting/Retching Attack | Intensity of Attack Scale (Efficacy Population) 12 hour, post-dose | 1.33 units on a scale | Standard Deviation 0.577 |
| 1mg AZ010 | Intensity of Vomiting/Retching Attack | Intensity of Attack Scale (Efficacy Population) 24 hour, post-dose | 2.20 units on a scale | Standard Deviation 0.837 |
| 1mg AZ010 | Intensity of Vomiting/Retching Attack | Intensity of Attack Scale (Efficacy Population) 6 hour, post-dose | 1.86 units on a scale | Standard Deviation 0.69 |
| 3mg AZ010 | Intensity of Vomiting/Retching Attack | Intensity of Attack Scale (Efficacy Population) 2 hours post-dose | 3.00 units on a scale | Standard Deviation 0.894 |
| 3mg AZ010 | Intensity of Vomiting/Retching Attack | Intensity of Attack Scale (Efficacy Population) 6 hour, post-dose | 2.29 units on a scale | Standard Deviation 0.756 |
| 3mg AZ010 | Intensity of Vomiting/Retching Attack | Intensity of Attack Scale (Efficacy Population) 12 hour, post-dose | 2.31 units on a scale | Standard Deviation 0.947 |
| 3mg AZ010 | Intensity of Vomiting/Retching Attack | Intensity of Attack Scale (Efficacy Population) 24 hour, post-dose | 2.38 units on a scale | Standard Deviation 0.916 |
| Placebo | Intensity of Vomiting/Retching Attack | Intensity of Attack Scale (Efficacy Population) 12 hour, post-dose | 1.75 units on a scale | Standard Deviation 0.957 |
| Placebo | Intensity of Vomiting/Retching Attack | Intensity of Attack Scale (Efficacy Population) 2 hours post-dose | 2.25 units on a scale | Standard Deviation 0.957 |
| Placebo | Intensity of Vomiting/Retching Attack | Intensity of Attack Scale (Efficacy Population) 6 hour, post-dose | 1.57 units on a scale | Standard Deviation 0.787 |
| Placebo | Intensity of Vomiting/Retching Attack | Intensity of Attack Scale (Efficacy Population) 24 hour, post-dose | 2.25 units on a scale | Standard Deviation 0.957 |
p-value: 0.9664Mixed Models Analysis
p-value: 0.7919Mixed Models Analysis
Secondary
Prior Episode Questionnaire
The duration of the CVS episode at 24 hours in relation to their typical CVS episodes (Prior Episode Questionnaire) and the intensity of the CVS episode at 24 hours in relation to their typical CVS episodes. A 3-point scale was used. The questions were prompted approximately 24 hours after each dose of study medication was administered. Duration: (Score definition: 1 = shorter duration than typical previous episode; 2 = same duration as typical previous episode; 3 = longer duration than typical previous episode) Intensity: (Score definition: 1 = less intense than typical previous episode; 2 = same intensity as typical previous episode; 3 = more intense than typical previous episode)
Time frame: 24 hours after each dose
Population: Per protocol population (CVS patients between 18 and 60 years of age who experienced at least 3 episodes of recurrent vomiting in the last 12 months and 2 episodes in the last 6 months.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1mg AZ010 | Prior Episode Questionnaire | Prior Episode Questionnaire, 24 Hours Post-Dose, Duration Of Current Episode | 1.46 score on a scale | Standard Deviation 0.658 |
| 1mg AZ010 | Prior Episode Questionnaire | Prior Episode Questionnaire, 24 Hours Post-Dose, Intensity Of Current Episode | 1.58 score on a scale | Standard Deviation 0.654 |
| 3mg AZ010 | Prior Episode Questionnaire | Prior Episode Questionnaire, 24 Hours Post-Dose, Duration Of Current Episode | 1.27 score on a scale | Standard Deviation 0.55 |
| 3mg AZ010 | Prior Episode Questionnaire | Prior Episode Questionnaire, 24 Hours Post-Dose, Intensity Of Current Episode | 1.55 score on a scale | Standard Deviation 0.671 |
| Placebo | Prior Episode Questionnaire | Prior Episode Questionnaire, 24 Hours Post-Dose, Duration Of Current Episode | 1.52 score on a scale | Standard Deviation 0.68 |
| Placebo | Prior Episode Questionnaire | Prior Episode Questionnaire, 24 Hours Post-Dose, Intensity Of Current Episode | 1.43 score on a scale | Standard Deviation 0.598 |
p-value: 0.8299Mixed Models Analysis
p-value: 0.2346Mixed Models Analysis
p-value: 0.3997Mixed Models Analysis
p-value: 0.3997Mixed Models Analysis
Secondary
Rescue Medication Use Within 1 Day of Dose
The percentage of patients who used rescue medication within the first day of treatment; patients confirming the individual had used some sort of rescue medication.
Time frame: 24 hours post dose
Population: Per protocol population (CVS patients between 18 and 60 years of age who experienced at least 3 episodes of recurrent vomiting in the last 12 months and 2 episodes in the last 6 months.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 1mg AZ010 | Rescue Medication Use Within 1 Day of Dose | Percentage of patients confirming Yes response to rescue medication use, 2 hours post dose | 3 Participants |
| 1mg AZ010 | Rescue Medication Use Within 1 Day of Dose | Percentage of patients confirming Yes response to rescue medication use, 24 hours post dose | 9 Participants |
| 3mg AZ010 | Rescue Medication Use Within 1 Day of Dose | Percentage of patients confirming Yes response to rescue medication use, 2 hours post dose | 2 Participants |
| 3mg AZ010 | Rescue Medication Use Within 1 Day of Dose | Percentage of patients confirming Yes response to rescue medication use, 24 hours post dose | 11 Participants |
| Placebo | Rescue Medication Use Within 1 Day of Dose | Percentage of patients confirming Yes response to rescue medication use, 2 hours post dose | 1 Participants |
| Placebo | Rescue Medication Use Within 1 Day of Dose | Percentage of patients confirming Yes response to rescue medication use, 24 hours post dose | 6 Participants |
p-value: 0.3847Mantel Haenszel
p-value: 0.1785Mantel Haenszel
Secondary
Rhodes Index of Nausea, Vomiting, and Retching (RINVR)
The Rhodes Index of nausea, vomiting, and retching (RINVR) at 6, 12, and 24 hours following treatment. The Rhodes Index of nausea, vomiting, and retching (RINVR) is designed to assess the degree of nausea distress and vomiting distress in patients. It is composed of 8 questions, and each question has 5 choices. The 5 choices for each individual question are scores from 0 to 4, with 0 being the lowest level without any symptoms related to nausea/vomiting/retching and 4 being the highest level. Individual question scores can be tracked over time, or a composite score with a total scoring range of 0 to 32 can be formed by adding the individual scores of the symptom occurrence and degree of discomfort questions together. Composite scores classified as follows: 0: no symptoms, 1-8: mild, 9-16: moderate, 17-24: great, 25-32: severe. This scale was adapted for the ePD, and patients were prompted to answer the questions according to the Schedule of Events.
Time frame: Within 24 hours following treatment.
Population: Per protocol population (CVS patients between 18 and 60 years of age who experienced at least 3 episodes of recurrent vomiting in the last 12 months and 2 episodes in the last 6 months.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1mg AZ010 | Rhodes Index of Nausea, Vomiting, and Retching (RINVR) | Rhodes Index of Nausea, Vomiting and Retching (RINVR) Composite Score, 12 hour, post-dose | 6.57 score on a scale | Standard Deviation 7.71 |
| 1mg AZ010 | Rhodes Index of Nausea, Vomiting, and Retching (RINVR) | Rhodes Index of Nausea, Vomiting and Retching (RINVR) Composite Score, 6 hour, post-dose | 11.20 score on a scale | Standard Deviation 7.741 |
| 1mg AZ010 | Rhodes Index of Nausea, Vomiting, and Retching (RINVR) | Rhodes Index of Nausea, Vomiting and Retching (RINVR) Composite Score, 24 hour, post-dose | 6.76 score on a scale | Standard Deviation 7.096 |
| 3mg AZ010 | Rhodes Index of Nausea, Vomiting, and Retching (RINVR) | Rhodes Index of Nausea, Vomiting and Retching (RINVR) Composite Score, 12 hour, post-dose | 10.45 score on a scale | Standard Deviation 9.237 |
| 3mg AZ010 | Rhodes Index of Nausea, Vomiting, and Retching (RINVR) | Rhodes Index of Nausea, Vomiting and Retching (RINVR) Composite Score, 6 hour, post-dose | 11.85 score on a scale | Standard Deviation 7.893 |
| 3mg AZ010 | Rhodes Index of Nausea, Vomiting, and Retching (RINVR) | Rhodes Index of Nausea, Vomiting and Retching (RINVR) Composite Score, 24 hour, post-dose | 8.87 score on a scale | Standard Deviation 8.471 |
| Placebo | Rhodes Index of Nausea, Vomiting, and Retching (RINVR) | Rhodes Index of Nausea, Vomiting and Retching (RINVR) Composite Score, 6 hour, post-dose | 11.79 score on a scale | Standard Deviation 7.695 |
| Placebo | Rhodes Index of Nausea, Vomiting, and Retching (RINVR) | Rhodes Index of Nausea, Vomiting and Retching (RINVR) Composite Score, 24 hour, post-dose | 7.92 score on a scale | Standard Deviation 8.057 |
| Placebo | Rhodes Index of Nausea, Vomiting, and Retching (RINVR) | Rhodes Index of Nausea, Vomiting and Retching (RINVR) Composite Score, 12 hour, post-dose | 7.81 score on a scale | Standard Deviation 8.274 |
Comparison: The RINVR is an 8-part questionnaire with each item scored from 0-4, for a total scoring range of 0-32. A lower score indicates less distress related to nausea, vomiting, and retching. The data shown is collected within the first 24 hours after the first at-home dose.p-value: 0.1337ANOVA
p-value: 0.7224ANOVA