Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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 not had prior PONV prophylaxis.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| APD421 standard | Experimental | Single (standard) dose IV APD421 |
|
| APD421 high | Experimental | Single (high) dose IV APD421 |
|
| Placebo | Placebo Comparator | Single IV placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| APD421 | Drug |
| ||
| Placebo |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 0-24 hours after treatment |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 0-2 hours after administration of study medication |
Not provided
Inclusion criteria:
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 low to moderate 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:
(i) have experienced a first episode of PONV not more than 24 hours after the end of their operation 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 agent likely to prevent or treat nausea or vomiting (given as prophylaxis or otherwise) in the period from 12 hours prior to the start of their operation up to the time of the qualifying PONV episode.
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Keith Candiotti, MD | University of Miami | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Jackson Memorial Hospital | Miami | Florida | 33136 | United States | ||
| Ohio State University |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31094774 | Derived | Candiotti KA, Kranke P, Bergese SD, Melson TI, Motsch J, Siddiqui N, Chung F, Rodriguez Y, Minkowitz HS, Ayad SS, Diemunsch P, Fox G. Randomized, Double-Blind, Placebo-Controlled Study of Intravenous Amisulpride as Treatment of Established Postoperative Nausea and Vomiting in Patients Who Have Had No Prior Prophylaxis. Anesth Analg. 2019 Jun;128(6):1098-1105. doi: 10.1213/ANE.0000000000003733. |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | APD421 Standard | Single (standard) dose IV APD421 |
| FG001 | APD421 High | Single (high) dose IV APD421 |
| FG002 | Placebo | Single IV placebo |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | APD421 5mg | APD421 5mg dose administered as a single, slow, intravenous (IV) push over about two minutes |
| BG001 | APD421 10mg | APD421 10mg dose administered as a single, slow, intravenous (IV) push over about two minutes |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Count of Participants | Participants | 0-24 hours after treatment |
|
7 days
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | APD421 5 mg | Single 5 mg dose IV APD421 | 0 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Postoperative ileus | Injury, poisoning and procedural complications | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Flatulence | Gastrointestinal disorders | Non-systematic Assessment |
There were no limitations or caveats associated with this study.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Gabriel Fox | Acacia Pharma Ltd | 01-223919764 | gabrielfox@acaciapharma.com |
Not provided
| ID | Term |
|---|---|
| D020250 | Postoperative Nausea and Vomiting |
| ID | Term |
|---|---|
| D011183 | Postoperative Complications |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D009325 | Nausea |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| Number of Participants With Complete Response 2-24 Hrs | Success of initial PONV treatment, where success is defined as no emetic episodes (vomiting or retching) and no administration of anti-emetic rescue medication from 2 to 24 hours after administration of study medication. | 2-24 hours after administration of study medication |
| Time to Treatment Failure | Time to first violation of the criteria for complete response | 0-24 hours after study drug administration |
| Number of Patients Experiencing 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 | 30 mins to 24 hours after study drug administration |
| Number of Participants Using Rescue Medication | Proportion of patients receiving pre-specified anti-emetic rescue medication at any time in the 24 hours post-treatment period | 0-24 hours after study drug administration |
| Incidence of Significant Nausea | Proportion 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. | 30 mins to 24 hours after study drug administration |
| Incidence of Nausea | Proportion 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. | 30 mins to 24 hours after study 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. | 30 mins to 24 hours after study drug administration |
| Evolution Score of Nausea (0-30 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 four pre-planned time points: pre-dose (0-min), and 5, 15 and 30 minutes 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. | 0-30 minutes after study drug administration |
| Columbus |
| Ohio |
| 43210 |
| United States |
| CHU de Hautepierre | Strasbourg | France |
| Universität Heidelberg | Heidelberg | Germany |
| BG002 | Placebo | Matching placebo administered as a single, slow, IV push over about two minutes |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| OG002 | Placebo | Single IV placebo administered as a single, slow, intravenous (IV) push over about two minutes. |
|
|
|
| Secondary | 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. | Posted | Count of Participants | Participants | 0-2 hours after administration of study medication |
|
|
|
|
| Secondary | Number of Participants With Complete Response 2-24 Hrs | Success of initial PONV treatment, where success is defined as no emetic episodes (vomiting or retching) and no administration of anti-emetic rescue medication from 2 to 24 hours after administration of study medication. | Posted | Count of Participants | Participants | 2-24 hours after administration of study medication |
|
|
|
|
| Secondary | Time to Treatment Failure | Time to first violation of the criteria for complete response | Posted | Median | Inter-Quartile Range | minutes | 0-24 hours after study drug administration |
|
|
|
|
| Secondary | Number of Patients Experiencing 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 | Posted | Count of Participants | Participants | 30 mins to 24 hours after study drug administration |
|
|
|
|
| Secondary | Number of Participants Using Rescue Medication | Proportion of patients receiving pre-specified anti-emetic rescue medication at any time in the 24 hours post-treatment period | Posted | Count of Participants | Participants | 0-24 hours after study drug administration |
|
|
|
|
| Secondary | Incidence of Significant Nausea | Proportion 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. | Posted | Count of Participants | Participants | 30 mins to 24 hours after study drug administration |
|
|
|
|
| Secondary | Incidence of Nausea | Proportion 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. | Posted | Count of Participants | Participants | 30 mins to 24 hours after study drug administration |
|
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | score on a scale | 30 mins to 24 hours after study drug administration |
|
|
|
|
| Secondary | Evolution Score of Nausea (0-30 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 four pre-planned time points: pre-dose (0-min), and 5, 15 and 30 minutes 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. | Posted | Mean | Full Range | Score on a scale*min | 0-30 minutes after study drug administration |
|
|
|
|
| 191 |
| 5 |
| 191 |
| 43 |
| 191 |
| EG001 | APD421 10 mg | Single 10 mg dose IV APD421 | 0 | 188 | 4 | 188 | 45 | 188 |
| EG002 | Placebo | Single IV placebo | 0 | 181 | 5 | 181 | 49 | 181 |
| Gastrointestinal anastomotic leak | Injury, poisoning and procedural complications | Non-systematic Assessment |
|
| Post procedural bile leak | Injury, poisoning and procedural complications | Non-systematic Assessment |
|
| Post procedural haematoma | Injury, poisoning and procedural complications | Non-systematic Assessment |
|
| Procedural pain | Injury, poisoning and procedural complications | Non-systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | Non-systematic Assessment |
|
| Abdominal abscess | Infections and infestations | Non-systematic Assessment |
|
| Peritonitis | Infections and infestations | Non-systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Tachyarrhythmia | Cardiac disorders | Non-systematic Assessment |
|
| Biliary colic | Hepatobiliary disorders | Non-systematic Assessment |
|
| Cerebellar infarction | Nervous system disorders | Non-systematic Assessment |
|
| Renal haemorrhage | Renal and urinary disorders | Non-systematic Assessment |
|
| Endometriosis | Reproductive system and breast disorders | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Non-systematic Assessment |
|
| Constipation | Gastrointestinal disorders | Non-systematic Assessment |
|
| Infusion site pain | General disorders | Non-systematic Assessment |
|
Not provided
Not provided
| D012817 | Signs and Symptoms, Digestive |
| D012816 | Signs and Symptoms |
| D014839 | Vomiting |
| 0.002 |
One-sided p-value. No adjustment for multiple comparisons. A priori threshold for statistical significance = 0.025. |
| Superiority |
| 0.552 |
One-sided p-value. No adjustment for multiple comparisons. A priori threshold for statistical significance = 0.025. |
| Superiority |
| Superiority |
| Superiority |
| Superiority |
| Superiority |
| Superiority |
| Superiority |
| Superiority |