Staccato Granisetron® (AZ 010) for the Treatment of Cyclic Vomiting Syndrome

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.

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.

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)

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 for care within the first day following dosing for a CVS episode.

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.

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

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).