Study of Intravenous Amisulpride for Prophylaxis of Post-operative Nausea and Vomiting (PONV) in Pediatric Patients

Nausea and Vomiting, Postoperative Clinical Trial

Official title:

Randomized, Double-blind, Phase 2/3 Study of IV Amisulpride as Prevention of Post-operative Nausea and Vomiting in Pediatric Patients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05546359
• Other study ID #: DP10027
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: January 18, 2024
• Est. completion date: December 30, 2025

Study information

• Verified date: April 2024
• Source: Acacia Pharma Ltd
• Contact: Gabriel Fox, MB BChir
• Phone: +44.7515.283700
• Email: Gabriel.Fox[@]amicuscd.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Randomized, double-blind, pediatric trial of amisulpride for prophylaxis of post operative nausea and vomiting

Description:

Randomized, double-blind, Phase 2/3 study of IV amisulpride as prevention of post-operative nausea and vomiting in pediatric patients

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 410
• Est. completion date: December 30, 2025
• Est. primary completion date: June 20, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Months to 17 Years

Eligibility

Inclusion Criteria:

1. Male or female patients aged from full-term birth to 17 years of age

2. Signed informed consent form and/or assent and willingness of patient and parents to participate in the trial

3. Patients undergoing non-emergency surgery, preferentially eye surgery, adenotonsillectomy or otoplasty, under general anesthesia (other than total intravenous anesthesia with propofol) expected to last at least 30 minutes from induction of anesthesia to removal of Endotracheal tube (ETT) or Laryngeal mask airway (LMA)

4. American Society of Anesthesiologists (ASA) risk score I-III

5. For females of child-bearing potential: ability and willingness to use a highly effective form of contraception (as defined in ICH M3 guidance, e.g., true (not periodic) abstinence from sexual intercourse, surgical sterilization (of subject or partner), combined oral contraceptive pill, or any other method or combination of methods with a failure rate generally considered to be <1% per year) between the date of screening and at least 48 hours after administration of study drug.

Exclusion Criteria:

1. Patients scheduled to undergo transplant or Central Nervous System (CNS) surgery

2. Patients scheduled to receive only a local anesthetic and/or regional neuraxial (intrathecal or epidural) block (without general anesthesia) or to receive general anesthesia involving total intravenous anesthesia (TIVA) with propofol

3. Patients who, in the opinion of the Investigator, are expected to remain ventilated for a significant period after surgery

4. Patients who are expected to need a naso- or orogastric tube in situ after surgery is completed

5. Patients who are expected to receive systemic pre/peri-operative corticosteroid therapy other than as anti-emetic prophylaxis

6. Patients receiving amisulpride for any indication within the 2 weeks prior to randomization

7. Patients known to be allergic to amisulpride or any of the excipients of amisulpride drug product; or to dexamethasone or ondansetron

8. Patients with a significant ongoing history of vestibular disease or dizziness

9. Patients being treated with regular anti-emetic therapy (dosed at least three times per week), which is still ongoing less than 1 week prior to screening

10. Patients being treated with levodopa, or any other dopamine D2-agonist

11. Patients who are pregnant or breast feeding

12. Patients with congenital long QT interval (QT) syndrome

13. Patients with a tumor of the anterior pituitary

14. Patients who have received emetogenic anti-cancer chemotherapy in the previous 4 weeks

15. Any other concurrent disease or illness that, in the opinion of the investigator makes the patient unsuitable for the study

16. Patients who have previously participated in this study or who have participated in another interventional clinical study involving pharmacological therapy within the previous 28 days (or longer exclusion period, if required by national or local regulations)

17. Where local laws/regulations require: patients under legal protection

Related Conditions & MeSH terms

• Nausea
• Nausea and Vomiting, Postoperative
• Postoperative Nausea and Vomiting
• Vomiting

Intervention

Drug:
• Amisulpride Injection
Dose finding treatment for continuation to phase 3
• Dexamethasone
Standard of care treatment

Locations

Country	Name	City	State
Canada	McGill University Health Centre - The Montréal Children's Hospital	Montréal	Quebec
Canada	The Hospital for Sick Children	Toronto	Ontario
France	HCL - Hôpital Mère Enfant	Bron
France	CHU Strasbourg - Hopital Hautepierre	Strasbourg
Germany	Helios Klinikum Aue	Aue
Germany	Universitaetsklinikum Bonn - Klinik für Anaesthesiologie & Operative Intensivmedizin	Bonn	Nordrhein-Westfalen
Germany	Ambulantes Operieren Marburg	Marburg	Hessen
Germany	Universitaetsklinikum Giessen und Marburg GmbH	Marburg	Hessen
Germany	Universitätsklinikum Würzburg	Würzburg	Bayern
United States	Emory Healthcare - Emory University Hospital	Atlanta	Georgia
United States	University of Minnesota Masonic Children's Hospital	Minneapolis	Minnesota
United States	The Children's Hospital of Philadelphia (CHOP)	Philadelphia	Pennsylvania
United States	UPMC Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	Helen Keller Hospital	Sheffield	Alabama

Sponsors (3)

Lead Sponsor	Collaborator
Acacia Pharma Ltd	Amicus CD LLC, Premier Research Group plc

Countries where clinical trial is conducted

United States,  Canada,  France,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluate Complete Response	Defined as no vomiting/retching (absence of PONV) and no use of anti-emetic rescue medication, during the first 24 hours after completion of surgery. Subjects will be questioned and assessed.	1 Day
Secondary	Occurrence of post-operative vomiting/retching	Subjects considered able to understand and provide a meaningful response should be asked if they have nausea ("feel sick" or other equivalent words) at the following times after completion of surgery (wound closure), unless an episode of PONV or discharge of the subject from the site has already occurred prior to the time point: 1 hour, 2 hours, 6 hours and 24 hours or when they first vomit, retch or receive rescue medication. In subjects aged = 6 years, at the above time points and for any spontaneously reported nausea episode, nausea severity should be scored using the validated 6-point Baxter Retching Faces (BARF) scale.	1 Day
Secondary	Use of rescue medication	Document use of rescue medication.	1 Day
Secondary	Occurrence and severity of post-operative nausea	An episode of nausea should be recorded any time that a subject spontaneously complains of nausea (including a request for rescue medication due to nausea). Subjects considered able to understand and provide a meaningful response should be asked if they have nausea ("feel sick" or other equivalent words) at the following times after completion of surgery (wound closure), unless an episode of PONV or discharge of the subject from the site has already occurred prior to the time point: 1 hour, 2 hours, 6 hours and 24 hours or when they first vomit, retch or receive rescue medication. In subjects aged = 6 years, at the above time points and for any spontaneously reported nausea episode, nausea severity should be scored using the validated 6-point Baxter Retching Faces (BARF) scale.	1 Day
Secondary	Time to emergence of PONV	Observe for, question and document emergence of vomiting/retching and nausea. In subjects aged = 6 years, at specified time points and for any spontaneously reported nausea episode, nausea severity should be scored using the validated 6-point Baxter Retching Faces (BARF) scale.	1 Day
Secondary	Time to emergence of vomiting/retching, significant nausea, and rescue medication, individually	Observe for emergence of vomiting/retching, determine significance of nausea, and note rescue medication, individually.	1 Day
Secondary	Different variables during different time ranges after the end of surgery (0-2 h, 2-6 h and 6-24 h)	Subjects considered able to understand and provide a meaningful response should be asked if they have nausea ("feel sick" or other equivalent words) at the following times after completion of surgery (wound closure), unless an episode of PONV or discharge of the subject from the site has already occurred prior to the time point: 1 hour, 2 hours, 6 hours and 24 hours or when they first vomit, retch or receive rescue medication. In subjects aged = 6 years, at the above time points and for any spontaneously reported nausea episode, nausea severity should be scored using the validated 6-point Baxter Retching Faces (BARF) scale.	1 Day
Secondary	The above variables in the sub-groups of patients who did and did not receive opioid analgesia	Concomitant medications will be reviewed.	1 Day
Secondary	Safety: The nature and frequency of adverse events and laboratory and electrocardiography (ECG) abnormalities	Adverse events, laboratory and ECG abnormalities will be noted. Blood samples should be drawn at screening (unless recent pre-existing results are available) and again post-operatively, as soon as practically possible after the patient's entry to the post-anesthesia care unit, recovery room or equivalent, and in any event within 1 hour after the end of surgery. Twelve-lead ECGs will be collected at screening. An ECG already taken as part of medical care within the period of 2 weeks prior to screening may be used to determine eligibility and to provide baseline ECG data.; In the peri-/post-operative period, continuous Holter monitoring of the ECG will be performed, from at least 10 minutes prior until at least 2 hours after the start of administration of amisulpride study medication.	7 Days
Secondary	Key pharmacokinetics parameter - Peak Plasma Concentration	Plasma samples will be drawn as required at specified timepoints to determine the PK profile of peak plasma concentration of amisulpride in subjects.	1 Day
Secondary	Key pharmacokinetics parameter - Total Exposure	Plasma samples will be drawn as required at specified timepoints to determine the PK profile of total exposure of amisulpride in subjects.	1 Day