Back to resultsA Study of Intravenous (IV) Amisulpride for Prophylaxis of Post-operative Nausea and Vomiting (PONV) in Pediatric Patients
Primary Purpose
Nausea and Vomiting, Postoperative
Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Amisulpride Injection [Barhemsys]
Dexamethasone
Sponsored by
About this trial
This is an interventional prevention trial for Nausea and Vomiting, Postoperative
Eligibility Criteria
Inclusion Criteria:
- Male or female patients aged from full-term birth to 17 years of age
- Signed informed consent form and/or assent and willingness of patient and parents to participate in the trial
- 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)
- American Society of Anesthesiologists (ASA) risk score I-III
- For females of child-bearing potential: ability and willingness to use a highly effective form of contraception (as defined in International Conference on Harmonization (ICH) M3 guidance, e.g., abstinence from sexual intercourse, surgical sterilization (of subject or partner), combined oral contraceptive pill, a double-barrier method of contraception such as either an intra-uterine device (IUD) or an occlusive cap with spermicide, in conjunction with partner's use of a condom, 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:
- Patients scheduled to undergo transplant or Central Nervous System (CNS) surgery
- 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
- Patients who, in the opinion of the Investigator, are expected to remain ventilated for a significant period after surgery
- Patients who are expected to need a naso- or orogastric tube in situ after surgery is completed
- Patients who are expected to receive systemic pre/peri-operative corticosteroid therapy other than as anti-emetic prophylaxis
- Patients receiving amisulpride for any indication within the 2 weeks prior to randomization
- Patients known to be allergic to amisulpride or any of the excipients of amisulpride drug product; or to dexamethasone or ondansetron
- Patients with a significant ongoing history of vestibular disease or dizziness
- 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
- Patients being treated with levodopa
- Patients who are pregnant or breast feeding
- Patients with congenital long QT interval (QT) syndrome
- Patients with a tumor of the anterior pituitary
- Patients who have received emetogenic anti-cancer chemotherapy in the previous 4 weeks
- Any other concurrent disease or illness that, in the opinion of the investigator makes the patient unsuitable for the study
- 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)
- Where local laws/regulations require: patients under legal protection
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Stage 1 - Group 1: IV amisulpride 0.035 mg/kg + IV dexamethasone
Stage 1 - Group 2: IV amisulpride 0.07 mg/kg + IV dexamethasone
Arm Description
Stage 1 - Group 1: IV amisulpride 0.035 mg/kg + IV dexamethasone
Stage 1 - Group 2: IV amisulpride 0.07 mg/kg + IV dexamethasone
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
Use of rescue medication
Document use of rescue medication.
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.
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.
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.
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.
The above variables in the sub-groups of patients who did and did not receive opioid analgesia
Concomitant medications will be reviewed.
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.
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.
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.
Full Information
NCT ID
NCT05546359
First Posted
September 12, 2022
Last Updated
April 24, 2023
Sponsor
Acacia Pharma Ltd
Collaborators
Amicus CD LLC, Premier Research Group plc
1. Study Identification
Unique Protocol Identification Number
NCT05546359
Brief Title
A Study of Intravenous (IV) Amisulpride for Prophylaxis of Post-operative Nausea and Vomiting (PONV) in Pediatric Patients
Official Title
Randomized, Double-blind, Phase 2/3 Study of IV Amisulpride as Prevention of Post-operative Nausea and Vomiting in Pediatric Patients
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
May 22, 2023 (Anticipated)
Primary Completion Date
June 20, 2024 (Anticipated)
Study Completion Date
December 30, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Acacia Pharma Ltd
Collaborators
Amicus CD LLC, Premier Research Group plc
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Randomized, double-blind, pediatric trial of amisulpride for prophylaxis of post operative nausea and vomiting
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Nausea and Vomiting, Postoperative
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
410 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Stage 1 - Group 1: IV amisulpride 0.035 mg/kg + IV dexamethasone
Arm Type
Experimental
Arm Description
Stage 1 - Group 1: IV amisulpride 0.035 mg/kg + IV dexamethasone
Arm Title
Stage 1 - Group 2: IV amisulpride 0.07 mg/kg + IV dexamethasone
Arm Type
Experimental
Arm Description
Stage 1 - Group 2: IV amisulpride 0.07 mg/kg + IV dexamethasone
Intervention Type
Drug
Intervention Name(s)
Amisulpride Injection [Barhemsys]
Intervention Description
Dose finding treatment for continuation to phase 3
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Intervention Description
Standard of care treatment
Primary Outcome Measure Information:
Title
Evaluate Complete Response
Description
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.
Time Frame
1 Day
Secondary Outcome Measure Information:
Title
Occurrence of post-operative vomiting/retching
Description
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.
Time Frame
1 Day
Title
Use of rescue medication
Description
Document use of rescue medication.
Time Frame
1 Day
Title
Occurrence and severity of post-operative nausea
Description
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.
Time Frame
1 Day
Title
Time to emergence of PONV
Description
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.
Time Frame
1 Day
Title
Time to emergence of vomiting/retching, significant nausea, and rescue medication, individually
Description
Observe for emergence of vomiting/retching, determine significance of nausea, and note rescue medication, individually.
Time Frame
1 Day
Title
Different variables during different time ranges after the end of surgery (0-2 h, 2-6 h and 6-24 h)
Description
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.
Time Frame
1 Day
Title
The above variables in the sub-groups of patients who did and did not receive opioid analgesia
Description
Concomitant medications will be reviewed.
Time Frame
1 Day
Title
Safety: The nature and frequency of adverse events and laboratory and electrocardiography (ECG) abnormalities
Description
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.
Time Frame
7 Days
Title
Key pharmacokinetics parameter - Peak Plasma Concentration
Description
Plasma samples will be drawn as required at specified timepoints to determine the PK profile of peak plasma concentration of amisulpride in subjects.
Time Frame
1 Day
Title
Key pharmacokinetics parameter - Total Exposure
Description
Plasma samples will be drawn as required at specified timepoints to determine the PK profile of total exposure of amisulpride in subjects.
Time Frame
1 Day
10. Eligibility
Sex
All
Minimum Age & Unit of Time
0 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female patients aged from full-term birth to 17 years of age
Signed informed consent form and/or assent and willingness of patient and parents to participate in the trial
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)
American Society of Anesthesiologists (ASA) risk score I-III
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:
Patients scheduled to undergo transplant or Central Nervous System (CNS) surgery
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
Patients who, in the opinion of the Investigator, are expected to remain ventilated for a significant period after surgery
Patients who are expected to need a naso- or orogastric tube in situ after surgery is completed
Patients who are expected to receive systemic pre/peri-operative corticosteroid therapy other than as anti-emetic prophylaxis
Patients receiving amisulpride for any indication within the 2 weeks prior to randomization
Patients known to be allergic to amisulpride or any of the excipients of amisulpride drug product; or to dexamethasone or ondansetron
Patients with a significant ongoing history of vestibular disease or dizziness
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
Patients being treated with levodopa, or any other dopamine D2-agonist
Patients who are pregnant or breast feeding
Patients with congenital long QT interval (QT) syndrome
Patients with a tumor of the anterior pituitary
Patients who have received emetogenic anti-cancer chemotherapy in the previous 4 weeks
Any other concurrent disease or illness that, in the opinion of the investigator makes the patient unsuitable for the study
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)
Where local laws/regulations require: patients under legal protection
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Gabriel Fox, MB BChir
Phone
+44.7515.283700
Email
Gabriel.Fox@amicuscd.com
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
A Study of Intravenous (IV) Amisulpride for Prophylaxis of Post-operative Nausea and Vomiting (PONV) in Pediatric Patients
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