Trial Outcomes & Findings for Study of APD421 as PONV Treatment (no Prior Prophylaxis) (NCT NCT02449291)
NCT ID: NCT02449291
Last Updated: 2019-01-22
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
568 participants
Primary outcome timeframe
0-24 hours after treatment
Results posted on
2019-01-22
Participant Flow
Participant milestones
| Measure |
APD421 Standard
Single (standard) dose IV APD421
|
APD421 High
Single (high) dose IV APD421
|
Placebo
Single IV placebo
|
|---|---|---|---|
|
Overall Study
STARTED
|
191
|
188
|
181
|
|
Overall Study
COMPLETED
|
186
|
186
|
180
|
|
Overall Study
NOT COMPLETED
|
5
|
2
|
1
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Study of APD421 as PONV Treatment (no Prior Prophylaxis)
Baseline characteristics by cohort
| Measure |
APD421 5mg
n=191 Participants
APD421 5mg dose administered as a single, slow, intravenous (IV) push over about two minutes
|
APD421 10mg
n=188 Participants
APD421 10mg dose administered as a single, slow, intravenous (IV) push over about two minutes
|
Placebo
n=181 Participants
Matching placebo administered as a single, slow, IV push over about two minutes
|
Total
n=560 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
44.2 years
n=5 Participants
|
47.4 years
n=7 Participants
|
46.5 years
n=5 Participants
|
46.1 years
n=4 Participants
|
|
Sex: Female, Male
Female
|
146 Participants
n=5 Participants
|
145 Participants
n=7 Participants
|
136 Participants
n=5 Participants
|
427 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
45 Participants
n=5 Participants
|
43 Participants
n=7 Participants
|
45 Participants
n=5 Participants
|
133 Participants
n=4 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Asian
|
7 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
14 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Black or African American
|
14 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
44 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
153 Participants
n=5 Participants
|
152 Participants
n=7 Participants
|
151 Participants
n=5 Participants
|
456 Participants
n=4 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
16 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
45 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: 0-24 hours after treatmentThe 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.
Outcome measures
| Measure |
APD421 5mg IV
n=191 Participants
APD421 (amisulpride) at 5mg administered as a single, slow, intravenous (IV) push over about two minutes.
|
APD421 10mg IV
n=188 Participants
APD421 (amisulpride) at 10 mg administered as a single, slow, intravenous (IV) push over about two minutes.
|
Placebo
n=181 Participants
Single IV placebo administered as a single, slow, intravenous (IV) push over about two minutes.
|
|---|---|---|---|
|
Complete Response (Success of Initial PONV Treatment)
|
60 Participants
|
59 Participants
|
39 Participants
|
SECONDARY outcome
Timeframe: 0-2 hours after administration of study medicationSuccess 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.
Outcome measures
| Measure |
APD421 5mg IV
n=191 Participants
APD421 (amisulpride) at 5mg administered as a single, slow, intravenous (IV) push over about two minutes.
|
APD421 10mg IV
n=188 Participants
APD421 (amisulpride) at 10 mg administered as a single, slow, intravenous (IV) push over about two minutes.
|
Placebo
n=181 Participants
Single IV placebo administered as a single, slow, intravenous (IV) push over about two minutes.
|
|---|---|---|---|
|
Number of Participants With Complete Response 0-2 Hrs
|
112 Participants
|
105 Participants
|
79 Participants
|
SECONDARY outcome
Timeframe: 2-24 hours after administration of study medicationSuccess 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.
Outcome measures
| Measure |
APD421 5mg IV
n=191 Participants
APD421 (amisulpride) at 5mg administered as a single, slow, intravenous (IV) push over about two minutes.
|
APD421 10mg IV
n=188 Participants
APD421 (amisulpride) at 10 mg administered as a single, slow, intravenous (IV) push over about two minutes.
|
Placebo
n=181 Participants
Single IV placebo administered as a single, slow, intravenous (IV) push over about two minutes.
|
|---|---|---|---|
|
Number of Participants With Complete Response 2-24 Hrs
|
100 Participants
|
109 Participants
|
96 Participants
|
SECONDARY outcome
Timeframe: 0-24 hours after study drug administrationTime to first violation of the criteria for complete response
Outcome measures
| Measure |
APD421 5mg IV
n=191 Participants
APD421 (amisulpride) at 5mg administered as a single, slow, intravenous (IV) push over about two minutes.
|
APD421 10mg IV
n=188 Participants
APD421 (amisulpride) at 10 mg administered as a single, slow, intravenous (IV) push over about two minutes.
|
Placebo
n=181 Participants
Single IV placebo administered as a single, slow, intravenous (IV) push over about two minutes.
|
|---|---|---|---|
|
Time to Treatment Failure
|
159 minutes
Interval 68.0 to
Treatment failure occurred in less than 75% of patients
|
177 minutes
Interval 53.5 to
Treatment failure occurred in less than 75% of patients
|
79 minutes
Interval 34.0 to 383.0
|
SECONDARY outcome
Timeframe: 30 mins to 24 hours after study drug administrationNumber of patients experiencing vomiting or retching during the time period from 30 minutes to 24 hours after administration of study medication
Outcome measures
| Measure |
APD421 5mg IV
n=191 Participants
APD421 (amisulpride) at 5mg administered as a single, slow, intravenous (IV) push over about two minutes.
|
APD421 10mg IV
n=188 Participants
APD421 (amisulpride) at 10 mg administered as a single, slow, intravenous (IV) push over about two minutes.
|
Placebo
n=181 Participants
Single IV placebo administered as a single, slow, intravenous (IV) push over about two minutes.
|
|---|---|---|---|
|
Number of Patients Experiencing Incidence of Emesis
|
64 Participants
|
57 Participants
|
62 Participants
|
SECONDARY outcome
Timeframe: 0-24 hours after study drug administrationProportion of patients receiving pre-specified anti-emetic rescue medication at any time in the 24 hours post-treatment period
Outcome measures
| Measure |
APD421 5mg IV
n=191 Participants
APD421 (amisulpride) at 5mg administered as a single, slow, intravenous (IV) push over about two minutes.
|
APD421 10mg IV
n=188 Participants
APD421 (amisulpride) at 10 mg administered as a single, slow, intravenous (IV) push over about two minutes.
|
Placebo
n=181 Participants
Single IV placebo administered as a single, slow, intravenous (IV) push over about two minutes.
|
|---|---|---|---|
|
Number of Participants Using Rescue Medication
|
121 Participants
|
119 Participants
|
135 Participants
|
SECONDARY outcome
Timeframe: 30 mins to 24 hours after study drug administrationProportion 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.
Outcome measures
| Measure |
APD421 5mg IV
n=191 Participants
APD421 (amisulpride) at 5mg administered as a single, slow, intravenous (IV) push over about two minutes.
|
APD421 10mg IV
n=188 Participants
APD421 (amisulpride) at 10 mg administered as a single, slow, intravenous (IV) push over about two minutes.
|
Placebo
n=181 Participants
Single IV placebo administered as a single, slow, intravenous (IV) push over about two minutes.
|
|---|---|---|---|
|
Incidence of Significant Nausea
|
114 Participants
|
108 Participants
|
115 Participants
|
SECONDARY outcome
Timeframe: 30 mins to 24 hours after study drug administrationProportion 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.
Outcome measures
| Measure |
APD421 5mg IV
n=191 Participants
APD421 (amisulpride) at 5mg administered as a single, slow, intravenous (IV) push over about two minutes.
|
APD421 10mg IV
n=188 Participants
APD421 (amisulpride) at 10 mg administered as a single, slow, intravenous (IV) push over about two minutes.
|
Placebo
n=181 Participants
Single IV placebo administered as a single, slow, intravenous (IV) push over about two minutes.
|
|---|---|---|---|
|
Incidence of Nausea
|
151 Participants
|
148 Participants
|
143 Participants
|
SECONDARY outcome
Timeframe: 30 mins to 24 hours after study drug administrationHighest 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.
Outcome measures
| Measure |
APD421 5mg IV
n=191 Participants
APD421 (amisulpride) at 5mg administered as a single, slow, intravenous (IV) push over about two minutes.
|
APD421 10mg IV
n=188 Participants
APD421 (amisulpride) at 10 mg administered as a single, slow, intravenous (IV) push over about two minutes.
|
Placebo
n=181 Participants
Single IV placebo administered as a single, slow, intravenous (IV) push over about two minutes.
|
|---|---|---|---|
|
Maximum Severity of Nausea
|
4.3 score on a scale
Standard Deviation 3.24
|
4.2 score on a scale
Standard Deviation 3.34
|
4.7 score on a scale
Standard Deviation 3.30
|
SECONDARY outcome
Timeframe: 0-30 minutes after study drug administrationThe 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.
Outcome measures
| Measure |
APD421 5mg IV
n=191 Participants
APD421 (amisulpride) at 5mg administered as a single, slow, intravenous (IV) push over about two minutes.
|
APD421 10mg IV
n=188 Participants
APD421 (amisulpride) at 10 mg administered as a single, slow, intravenous (IV) push over about two minutes.
|
Placebo
n=181 Participants
Single IV placebo administered as a single, slow, intravenous (IV) push over about two minutes.
|
|---|---|---|---|
|
Evolution Score of Nausea (0-30 Mins)
|
1440.79 Score on a scale*min
Interval 250.0 to 3450.0
|
1502.55 Score on a scale*min
Interval 250.0 to 5375.0
|
1661.25 Score on a scale*min
Interval 250.0 to 5812.5
|
Adverse Events
APD421 5 mg
Serious events: 5 serious events
Other events: 43 other events
Deaths: 0 deaths
APD421 10 mg
Serious events: 4 serious events
Other events: 45 other events
Deaths: 0 deaths
Placebo
Serious events: 5 serious events
Other events: 49 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
APD421 5 mg
n=191 participants at risk
Single 5 mg dose IV APD421
|
APD421 10 mg
n=188 participants at risk
Single 10 mg dose IV APD421
|
Placebo
n=181 participants at risk
Single IV placebo
|
|---|---|---|---|
|
Injury, poisoning and procedural complications
Postoperative ileus
|
0.52%
1/191 • Number of events 1 • 7 days
|
0.53%
1/188 • Number of events 1 • 7 days
|
0.00%
0/181 • 7 days
|
|
Injury, poisoning and procedural complications
Gastrointestinal anastomotic leak
|
0.00%
0/191 • 7 days
|
0.00%
0/188 • 7 days
|
0.55%
1/181 • Number of events 1 • 7 days
|
|
Injury, poisoning and procedural complications
Post procedural bile leak
|
0.00%
0/191 • 7 days
|
0.53%
1/188 • Number of events 1 • 7 days
|
0.00%
0/181 • 7 days
|
|
Injury, poisoning and procedural complications
Post procedural haematoma
|
0.52%
1/191 • Number of events 1 • 7 days
|
0.00%
0/188 • 7 days
|
0.00%
0/181 • 7 days
|
|
Injury, poisoning and procedural complications
Procedural pain
|
0.52%
1/191 • Number of events 1 • 7 days
|
0.00%
0/188 • 7 days
|
0.00%
0/181 • 7 days
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/191 • 7 days
|
0.00%
0/188 • 7 days
|
0.55%
1/181 • Number of events 1 • 7 days
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/191 • 7 days
|
0.00%
0/188 • 7 days
|
0.55%
1/181 • Number of events 1 • 7 days
|
|
Infections and infestations
Abdominal abscess
|
0.52%
1/191 • Number of events 1 • 7 days
|
0.00%
0/188 • 7 days
|
0.00%
0/181 • 7 days
|
|
Infections and infestations
Peritonitis
|
0.00%
0/191 • 7 days
|
0.00%
0/188 • 7 days
|
0.55%
1/181 • Number of events 1 • 7 days
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/191 • 7 days
|
0.00%
0/188 • 7 days
|
0.55%
1/181 • Number of events 1 • 7 days
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.52%
1/191 • Number of events 1 • 7 days
|
0.00%
0/188 • 7 days
|
0.00%
0/181 • 7 days
|
|
Cardiac disorders
Tachyarrhythmia
|
0.00%
0/191 • 7 days
|
0.53%
1/188 • Number of events 1 • 7 days
|
0.00%
0/181 • 7 days
|
|
Hepatobiliary disorders
Biliary colic
|
0.00%
0/191 • 7 days
|
0.53%
1/188 • Number of events 1 • 7 days
|
0.00%
0/181 • 7 days
|
|
Nervous system disorders
Cerebellar infarction
|
0.00%
0/191 • 7 days
|
0.00%
0/188 • 7 days
|
0.55%
1/181 • Number of events 1 • 7 days
|
|
Renal and urinary disorders
Renal haemorrhage
|
0.00%
0/191 • 7 days
|
0.00%
0/188 • 7 days
|
0.55%
1/181 • Number of events 1 • 7 days
|
|
Reproductive system and breast disorders
Endometriosis
|
0.52%
1/191 • Number of events 1 • 7 days
|
0.00%
0/188 • 7 days
|
0.00%
0/181 • 7 days
|
Other adverse events
| Measure |
APD421 5 mg
n=191 participants at risk
Single 5 mg dose IV APD421
|
APD421 10 mg
n=188 participants at risk
Single 10 mg dose IV APD421
|
Placebo
n=181 participants at risk
Single IV placebo
|
|---|---|---|---|
|
Gastrointestinal disorders
Flatulence
|
12.6%
24/191 • Number of events 25 • 7 days
|
9.0%
17/188 • Number of events 17 • 7 days
|
11.6%
21/181 • Number of events 21 • 7 days
|
|
Gastrointestinal disorders
Nausea
|
7.9%
15/191 • Number of events 17 • 7 days
|
9.6%
18/188 • Number of events 18 • 7 days
|
10.5%
19/181 • Number of events 22 • 7 days
|
|
Gastrointestinal disorders
Constipation
|
7.3%
14/191 • Number of events 14 • 7 days
|
6.9%
13/188 • Number of events 13 • 7 days
|
8.8%
16/181 • Number of events 16 • 7 days
|
|
General disorders
Infusion site pain
|
4.2%
8/191 • Number of events 8 • 7 days
|
6.9%
13/188 • Number of events 13 • 7 days
|
3.9%
7/181 • Number of events 7 • 7 days
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place