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

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

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.

Study Overview

• Status: Completed
• Conditions: Cyclic Vomiting Syndrome
• Intervention / Treatment: Combination product: 1mg AZ010; Combination product: 3mg AZ-010; Combination product: Staccato Placebo

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

• Study Type: Interventional
• Enrollment (Actual): 150
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Lancaster, California, United States, 93535
      • Om Research
    • Los Angeles, California, United States, 90036
      • Axis Clinical Trials
    • San Diego, California, United States, 92114
      • Precision Research Institute, LLC
  • Florida
    • Tampa, Florida, United States, 33606
      • University of South Florida
  • Georgia
    • Athens, Georgia, United States, 30607
      • Summit Clinical Studies
    • Morrow, Georgia, United States, 30260
      • Infinite Clinical Trials
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Kansas University Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • New York
    • Brooklyn, New York, United States, 11235
      • NY Scientific
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University Hospital
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center
  • Tennessee
    • Knoxville, Tennessee, United States, 37909
      • New Phase Research & Development, LLC
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • Houston, Texas, United States, 77099
      • Pioneer Research Solutions
    • Kerrville, Texas, United States, 78028
      • Sante Clinical Research
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 56 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1mg AZ010; Single orally-inhaled dose	Combination product: 1mg AZ010; Subjects who received a single inhaled dose (1mg)
Experimental: 3mg AZ010; Single orally-inhaled dose	Combination product: 3mg AZ-010; Subjects who received a single inhaled dose (3mg)
Experimental: Placebo; Single orally-inhaled dose	Combination product: Staccato Placebo; Subject who received a single inhaled dose (Staccato Placebo)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Within the following timepoints: 30, 60, 90 and 120-minutes post-dose.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	24 hours after treatment dose
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)	24 hours after each dose
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.	24 hours post dose
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.	Within Day 1 after dosing
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.	Within 24 hours following treatment.
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	Up to 24 hours post dose.
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).	Within 24 hours post dose.

Collaborators and Investigators

• Sponsor: Alexza Pharmaceuticals, Inc.
• Investigators: Study Director: Larry Carter, PhD, Alexza Pharmaceuticals, Inc.

Publications and helpful links

Helpful Links

• CVS study web-site

Study record dates

Study Major Dates

• Study Start (Actual): February 5, 2021
• Primary Completion (Actual): July 26, 2022
• Study Completion (Actual): July 26, 2022

Study Registration Dates

• First Submitted: November 16, 2020
• First Submitted That Met QC Criteria: November 25, 2020
• First Posted (Actual): November 27, 2020

Study Record Updates

• Last Update Posted (Actual): June 11, 2025
• Last Update Submitted That Met QC Criteria: June 10, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Nausea; Vomiting; CVS; Retching; Cyclic Vomiting Syndrome; Abdominal migraine; Stomach pain; Unexplained vomiting; Functional GI Disorder; CVSHOPE.com; Throwing up; Puking; Dry heaving; Food poisoning; Episodes; Repeated food poisoning
• Additional Relevant MeSH Terms: Pathologic Processes; Signs and Symptoms, Digestive; Disease; Syndrome; Vomiting
• Other Study ID Numbers: AMDC 010-201

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes