Postoperative Nausea and VomitingPhase 3NCT02646566
Study of APD421 as PONV Treatment (Prior Prophylaxis)
A Phase 3 study testing APD421 in people with Postoperative Nausea and Vomiting, run by Acacia Pharma Ltd at 8 sites in 3 countries.
Trial summary
Double-blind, randomised, parallel-group, placebo-controlled, adaptive, seamless, dose-selecting study to compare the efficacy of APD421 to placebo as treatment of established PONV, in patients who have had prior PONV prophylaxis. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Postoperative Nausea and Vomiting
- What is being tested?
- APD421
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 705 participants
- Where
- 8 sitesin 3 countries
- Study dates
- Mar 2016to Jan 2017
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female patients ≥ 18 years of age
- Provision of written informed consent
- Patients scheduled to undergo elective surgery (open or laparoscopic technique) under general anaesthesia (other than total intravenous anaesthesia with propofol) expected to last at least one hour from induction of anaesthesia to extubation
- Patients judged by the investigator to have a moderate or high risk of experiencing PONV. In forming this judgment, investigators should pay particular attention to risk factors such as a past history of PONV and/or motion sickness; habitual non-smoking status; female sex; and likely use of opioid analgesia post-operatively.
- 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., abstinence from sexual intercourse, surgical sterilisation (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
- In order to be eligible for randomisation, subjects must also:
- have experienced a first episode of PONV not more than 24 hours after the end of their operation (wound closure) and prior to discharge from hospital ("qualifying PONV episode"), for which they have not already received any anti-emetic treatment; and (ii) not have received any dopamine-antagonist agent likely to prevent or treat nausea or vomiting (given as prophylaxis or otherwise) in the period from 24 hours prior to the start of their operation up to the time of the qualifying PONV episode.
Who cannot join
- Patients scheduled to undergo transplant surgery or any surgery where post-operative emesis may pose a significant danger to the patient
- Patients planned to receive only a local anaesthetic and/or regional neuraxial (intrathecal or epidural) block
- Patients who have received APD421 active ingredient for any indication within the last 2 weeks
- Patients who are allergic to APD421 active ingredient or any of the excipients of APD421
- Patients with a significant, ongoing history of vestibular disease or dizziness
- Patients with a known prolactin-dependent tumour (e.g. pituitary gland prolactinoma or breast cancer) or phaeochromocytoma.
Show all 18Show fewer
- Patients with documented or suspected alcohol or substance abuse within the past 6 months.
- Patients with direct or indirect evidence of clinically significant hypokalaemia, such as a serum potassium level < 3.0 mmol/L.
- Patients who have received in the post-operative period, and prior to receiving study drug, any medication with a substantial risk of inducing torsades de pointes, including Class Ia antiarrhythmic agents such as quinidine, disopyramide, procainamide; Class III antiarrhythmic agents such as amiodarone and sotalol; and other medications such as bepridil, cisapride, thioridazine, methadone, IV erythromycin, IV vincamine, halofantrine, pentamidine, sparfloxacin, etc.
- Patients who have a documented, clinically significant cardiac arrhythmia or congenital long QT syndrome.
- Patients who are pregnant or breast feeding.
- Patients being treated with levodopa.
- Patients diagnosed with Parkinson's disease.
- Patients who have received emetogenic anti-cancer chemotherapy in the previous 4 weeks.
- Patients with a history of epilepsy.
- 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.
Trial locations and contacts
8 sites in 3 countries.
8 sites in 3 countries
United States4 sites
Ohio State University
Columbus, Ohio, 43210
Duke University Medical Center
Durham, North Carolina, 27710
Jackson Memorial Hospital
Miami, Florida, 33136
Wake Forest University School of Medicine
Winston-Salem, North Carolina, 27157
Germany3 sites
HELIOS Klinikum Aue
Aue, 08280
Universität Heidelberg
Heidelberg
Philipps University
Marburg
About this study
Official title: Randomised, Double-blind, Placebo-controlled Study of APD421 (Amisulpride for IV Injection) as Treatment of Established Post-operative Nausea and Vomiting, in Patients Who Have Had Prior Prophylaxis
Double-blind, randomised, parallel-group, placebo-controlled, adaptive, seamless, dose-selecting study to compare the efficacy of APD421 to placebo as treatment of established PONV, in patients who have had prior PONV prophylaxis.
- Conditions
- Postoperative Nausea and Vomiting
- Being tested
- APD421, Placebo
- Medical subject headings
- Postoperative Nausea and Vomiting
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
APD421Drug
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| APD421 standard | Experimental | Single (standard) dose IV APD421 Receives: Drug: APD421 |
| APD421 high | Experimental | Single (high) dose IV APD421 Receives: Drug: APD421 |
| Placebo | Placebo comparator | Single IV placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Complete Response (Success of Initial PONV Treatment)
The primary efficacy variable was the dichotomous variable: success or failure of initial PONV treatment, where success is defined as no emetic episodes (vomiting or retching) from 30 minutes* to 24 hours after administration of study medication and no administration of anti-emetic rescue medication at any time in the 24-hour period after administration of study medication.
Measured: 0-24 hours after administration of study medication
Secondary outcomes (10)
Number of Participants With Complete Response 0-2 Hrs
Success of initial PONV treatment, where success is defined as no emetic episodes (vomiting or retching) from 30 minutes* to 2 hours after administration of study medication and no administration of anti-emetic rescue medication at any time in the 2-hour period after administration of study medication.
Measured: 0-2 hours after administration of study medication
Number of Participants With Complete Response 0-4 Hrs
Success of initial PONV treatment, where success is defined as no emetic episodes (vomiting or retching) from 30 minutes* to 4 hours after administration of study medication and no administration of anti-emetic rescue medication at any time in the 4-hour period after administration of study medication.
Measured: 0-4 hours after administration of study medication
Number of Participants With Complete Response 0-6 Hrs
Success of initial PONV treatment, where success is defined as no emetic episodes (vomiting or retching) from 30 minutes to 6 hours after administration of study medication and no administration of anti-emetic rescue medication at any time in the 6-hour period after administration of study medication.
Measured: 0-6 hours after administration of study medication
Time to Treatment Failure
Time to first violation of the criteria for complete response
Measured: 0-24 hours after study drug administration
Number of Patients With Incidence of Emesis
Number of patients experiencing vomiting or retching during the time period from 30 minutes to 24 hours after administration of study medication
Measured: 30 mins to 24 hours after study drug administration
Number of Patients Receiving Rescue Medication
Number of patients receiving pre-specified anti-emetic rescue medication at any time in the 24 hours post-treatment period
Measured: 0-24 hours after study drug administration
Number of Patients With an Incidence of Significant Nausea
Number of patients with nausea score ≥4 on an 11-point verbal rating scale (0=no nausea, 10=worst possible nausea, therefore higher value is worse outcome) during the time period from 30 minutes to 24 hours after administration of study medication.
Measured: 30 mins to 24 hours after study drug administration
Number of Patients With an Incidence of Nausea
Number of patients with nausea score ≥1 on an 11-point verbal rating scale (0=no nausea, 10=worst possible nausea, therefore higher value is worse outcome) during the time period from 30 minutes to 24 hours after administration of study medication.
Measured: 30 mins to 24 hours after drug administration
Maximum Severity of Nausea
Highest recorded nausea score on an 11-point verbal rating scale (0=no nausea, 10=worst possible nausea, therefore higher value is worse outcome) during the time period from 30 minutes to 24 hours after administration of study medication.
Measured: 30 mins to 24 hours after study drug administration
Evolution Score of Nausea (0-180 Mins)
The evolution score of nausea was calculated as the area under the curve (AUC) of the nausea scores on a scale 0-10 (where 0 is no nausea and 10 is the worst nausea imaginable) obtained at five pre-planned time points: pre-dose (0-min), and 5, 15 and 30 minutes and 2 hours after administration of study medication, as well as any spontaneously reported episodes of nausea during the time period, plotted against time. A higher score represents a worse outcome.
Measured: 0-180 minutes after study drug administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jan 2016 (estimated)
- Study startMar 2016
- Primary completionJan 2017
- Study completionJan 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Postoperative Nausea and VomitingStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 705 participants (actual)
Sponsor and investigators
- Lead sponsor
- Acacia Pharma Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Gabriel Fox, MB BChir, Study director, Acacia Pharma Ltd
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02646566
- Sponsor's protocol ID
- DP10019
- Status last verified
- Jan 2019
- First submitted
- 4 Jan 2016
- Last updated
- 22 Jan 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomised, Double-blind, Placebo-controlled Study of APD421 (Amisulpride for IV Injection) as Treatment of Established Post-operative Nausea and Vomiting, in Patients Who Have Had Prior Prophylaxis
- ClinicalTrials.gov ID
- NCT02646566
- Acronym / sponsor ID
- DP10019
- Conditions
- Postoperative Nausea and Vomiting
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 705 participants (actual)
- Lead sponsor
- Acacia Pharma LtdIndustry (pharma, biotech, devices)
- Study start
- Mar 2016 (actual)
- Primary completion
- Jan 2017 (actual)
- Study completion
- Jan 2017 (actual)
- First posted
- 5 Jan 2016 (estimated)
- Results
- Posted 19 Dec 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Double-blind, randomised, parallel-group, placebo-controlled, adaptive, seamless, dose-selecting study to compare the efficacy of APD421 to placebo as treatment of established PONV, in patients who have had prior PONV prophylaxis.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| APD421 standard | Experimental | Drug: APD421Single (standard) dose IV APD421 |
| APD421 high | Experimental | Drug: APD421Single (high) dose IV APD421 |
| Placebo | Placebo comparator | Drug: PlaceboSingle IV placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Male or female patients ≥ 18 years of age
- Provision of written informed consent
- Patients scheduled to undergo elective surgery (open or laparoscopic technique) under general anaesthesia (other than total intravenous anaesthesia with propofol) expected to last at least one hour from induction of anaesthesia to extubation
- Patients judged by the investigator to have a moderate or high risk of experiencing PONV. In forming this judgment, investigators should pay particular attention to risk factors such as a past history of PONV and/or motion sickness; habitual non-smoking status; female sex; and likely use of opioid analgesia post-operatively.
- 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., abstinence from sexual intercourse, surgical sterilisation (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
Key exclusion criteria (18 listed)
- Patients scheduled to undergo transplant surgery or any surgery where post-operative emesis may pose a significant danger to the patient
- Patients planned to receive only a local anaesthetic and/or regional neuraxial (intrathecal or epidural) block
- Patients who have received APD421 active ingredient for any indication within the last 2 weeks
- Patients who are allergic to APD421 active ingredient or any of the excipients of APD421
- Patients with a significant, ongoing history of vestibular disease or dizziness
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| APD421 | Drug | APD421 high, APD421 standard |
| Placebo | Drug | Placebo |
Primary outcome
Number of Participants With Complete Response (Success of Initial PONV Treatment)
Time frame: 0-24 hours after administration of study medication
The primary efficacy variable was the dichotomous variable: success or failure of initial PONV treatment, where success is defined as no emetic episodes (vomiting or retching) from 30 minutes* to 24 hours after administration of study medication and no administration of anti-emetic rescue medication at any time in the 24-hour period after administration of study medication.
10 secondary outcomes
Number of Participants With Complete Response 0-2 Hrs
Time frame: 0-2 hours after administration of study medication
Number of Participants With Complete Response 0-4 Hrs
Time frame: 0-4 hours after administration of study medication
Number of Participants With Complete Response 0-6 Hrs
Time frame: 0-6 hours after administration of study medication
Time to Treatment Failure
Time frame: 0-24 hours after study drug administration
Number of Patients With Incidence of Emesis
Time frame: 30 mins to 24 hours after study drug administration
Number of Patients Receiving Rescue Medication
Time frame: 0-24 hours after study drug administration
Number of Patients With an Incidence of Significant Nausea
Time frame: 30 mins to 24 hours after study drug administration
Number of Patients With an Incidence of Nausea
Time frame: 30 mins to 24 hours after drug administration
Maximum Severity of Nausea
Time frame: 30 mins to 24 hours after study drug administration
Evolution Score of Nausea (0-180 Mins)
Time frame: 0-180 minutes after study drug administration
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jan 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gabriel Fox, MB BChir study director
Acacia Pharma Ltd
8 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing APD421 in people with Postoperative Nausea and Vomiting, run by Acacia Pharma Ltd at 8 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States, Germany, France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Dec 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Complete Response (Success of Initial PONV Treatment) (time frame: 0-24 hours after administration of study medication). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jan 2019.