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US Phase III Study of APD421 in PONV

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01991860
Recruitment Status : Completed
First Posted : November 25, 2013
Results First Posted : September 6, 2018
Last Update Posted : February 12, 2019
Sponsor:
Information provided by (Responsible Party):
Acacia Pharma Ltd

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Prevention
Condition PONV
Interventions Drug: APD421- Amisulpride for IV injection
Drug: Placebo
Enrollment 364
Recruitment Details  
Pre-assignment Details Of the 364 patients enrolled in the study (i.e. signed informed consent form), 22 patients were not randomised and not dosed. Of these, 4 withdrew their consent, 3 did not comply with the protocol procedures and 15 were not dosed for other unspecified reasons.
Arm/Group Title 5mg APD421 Placebo
Hide Arm/Group Description A 5mg (2mL) dose of APD421 given by slow intravenous (IV) push over one minute at induction of anaesthesia 2mL of placebo given by slow intravenous (IV) push over one minute at induction of anaesthesia
Period Title: Overall Study
Started 176 166
Completed 172 164
Not Completed 4 2
Arm/Group Title 5mg Dose APD421 Placebo Total
Hide Arm/Group Description A 5mg dose of APD421 given by slow push, single intravenous (IV) administration over a time frame of one minute at induction of anaesthesia Single dose placebo given through intravenous (IV) administration Total of all reporting groups
Overall Number of Baseline Participants 176 166 342
Hide Baseline Analysis Population Description
A total of 342 patients were randomised and dosed, comprising 176 randomised to APD421 and 166 to placebo. Of these, 4 patients from the APD421 group and 2 patients from the placebo group discontinued prematurely after randomisation
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 176 participants 166 participants 342 participants
54.5  (14.2) 53.0  (13.7) 53.8  (13.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 176 participants 166 participants 342 participants
Female
114
  64.8%
110
  66.3%
224
  65.5%
Male
62
  35.2%
56
  33.7%
118
  34.5%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 176 participants 166 participants 342 participants
176 166 342
1.Primary Outcome
Title Number of Participants With Complete Response
Hide Description The primary efficacy analysis was a comparison of the incidence of Complete Response, defined as no emesis (vomiting or retching) and no use of rescue medication in the 24 hours after the end of surgery, between the active group and the placebo group using Pearson χ2 test with Yates's continuity correction, and with a two-sided significance level of 5%.
Time Frame 24 hours after the end of surgery
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title APD421 at 5mg Placebo
Hide Arm/Group Description:
A 5mg (2mL) dose of APD421 given by slow intravenous (IV) push over one minute at induction of anaesthesia
A 2mL dose of placebo given by slow intravenous (IV) push over one minute at induction of anaesthesia
Overall Number of Participants Analyzed 176 166
Measure Type: Count of Participants
Unit of Measure: Participants
78
  44.3%
54
  32.5%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection APD421 at 5mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.033
Comments 2-sided
Method Chi-squared, Corrected
Comments Yates’s continuity correction
2.Secondary Outcome
Title Number of Participants With no Nausea.
Hide Description Nausea (defined as the desire to vomit without the presence of expulsive muscular movements) measured on a 0-10 verbal response scale, where 0=no nausea at all and 10=the worst nausea imaginable. "No nausea" means no score ≥ 1.
Time Frame 24 hours after end of surgery
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title APD421 at 5mg Placebo
Hide Arm/Group Description:
A 5mg (2mL) dose of APD421 given by slow intravenous (IV) push over one minute at induction of anaesthesia
A 2mL dose of placebo given by slow intravenous (IV) push over one minute at induction of anaesthesia
Overall Number of Participants Analyzed 176 166
Measure Type: Count of Participants
Unit of Measure: Participants
82
  46.6%
64
  38.6%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection APD421 at 5mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.16
Comments [Not Specified]
Method Chi-squared, Corrected
Comments Yates’s continuity correction
3.Secondary Outcome
Title Number of Participants With no Emesis
Hide Description Emesis is defined as vomiting (production of even the smallest amount of stomach contents) or retching (muscular movements of vomiting but without expulsion of stomach contents, usually because of an empty stomach)
Time Frame 24 hours after end of surgery
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title APD421 at 5mg Placebo
Hide Arm/Group Description:
A 5mg (2mL) dose of APD421 given by slow intravenous (IV) push over one minute at induction of anaesthesia
A 2mL dose of placebo given by slow intravenous (IV) push over one minute at induction of anaesthesia
Overall Number of Participants Analyzed 176 166
Measure Type: Count of Participants
Unit of Measure: Participants
141
  80.1%
129
  77.7%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection APD421 at 5mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.68
Comments [Not Specified]
Method Chi-squared, Corrected
Comments Yates’s continuity correction
4.Secondary Outcome
Title Number of Participants With no Use of Rescue Medication
Hide Description Any agent given in the post-operative period with the intention of providing anti-emetic rescue was counted as rescue anti-emetic medication for the purposes of efficacy determination, even if it did not achieve control of emesis or was given incorrectly (e.g., wrong dosage or route). Any agent given in the post-operative period which would be expected, by virtue of its pharmacology, dosage and route, to exert a clinically meaningful anti-emetic effect was considered as rescue anti-emetic medication, even if administered inadvertently or without the intention of providing rescue.
Time Frame 24 hours after end of surgery
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title APD421 at 5mg Placebo
Hide Arm/Group Description:
A 5mg (2mL) dose of APD421 given by slow intravenous (IV) push over one minute at induction of anaesthesia
A 2mL dose of placebo given by slow intravenous (IV) push over one minute at induction of anaesthesia
Overall Number of Participants Analyzed 176 166
Measure Type: Count of Participants
Unit of Measure: Participants
80
  45.5%
55
  33.1%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection APD421 at 5mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.026
Comments [Not Specified]
Method Chi-squared, Corrected
Comments Yates’s continuity correction
5.Secondary Outcome
Title The Number of Participants With no Emesis, no Significant Nausea and no Use of Rescue Medication
Hide Description No occurrence of vomiting/retching, no nausea score ≥ 4 on verbal response scale (where 0=no nausea at all and 10=the worst nausea imaginable) and no use of rescue medication.
Time Frame 24 hours after the end of surgery
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title APD421 at 5mg Placebo
Hide Arm/Group Description:
A 5mg (2mL) dose of APD421 given by slow intravenous (IV) push over one minute at induction of anaesthesia
A 2mL dose of placebo given by slow intravenous (IV) push over one minute at induction of anaesthesia
Overall Number of Participants Analyzed 176 166
Measure Type: Count of Participants
Unit of Measure: Participants
73
  41.5%
53
  31.9%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection APD421 at 5mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.086
Comments [Not Specified]
Method Chi-squared, Corrected
Comments Yates’s continuity correction
6.Secondary Outcome
Title The Number of Participants With no Significant Nausea
Hide Description Nausea (defined as the desire to vomit without the presence of expulsive muscular movements) measured on a 0-10 verbal response scale, where 0=no nausea at all and 10=the worst nausea imaginable. "No significant nausea" means no score ≥ 4.
Time Frame 24 hours after the end of surgery
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title APD421 at 5mg Placebo
Hide Arm/Group Description:
A 5mg (2mL) dose of APD421 given by slow intravenous (IV) push over one minute at induction of anaesthesia
A 2mL dose of placebo given by slow intravenous (IV) push over one minute at induction of anaesthesia
Overall Number of Participants Analyzed 176 166
Measure Type: Count of Participants
Unit of Measure: Participants
107
  60.8%
84
  50.6%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection APD421 at 5mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.074
Comments [Not Specified]
Method Chi-squared, Corrected
Comments Yates’s continuity correction
7.Secondary Outcome
Title Number of Participants With "Total Response"
Hide Description Total response is defined as no occurrence of vomiting/retching, no nausea score ≥ 1 and no use of rescue medication.
Time Frame 24 hours after the end of surgery
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title APD421 at 5mg Placebo
Hide Arm/Group Description:
A 5mg (2mL) dose of APD421 given by slow intravenous (IV) push over one minute at induction of anaesthesia
A 2mL dose of placebo given by slow intravenous (IV) push over one minute at induction of anaesthesia
Overall Number of Participants Analyzed 176 166
Measure Type: Count of Participants
Unit of Measure: Participants
67
  38.1%
50
  30.1%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection APD421 at 5mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.15
Comments [Not Specified]
Method Chi-squared, Corrected
Comments Yates’s continuity correction
Time Frame 7 days
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title APD421 5mg Dose Placebo
Hide Arm/Group Description A 5mg dose of APD421 given by slow push, single intravenous (IV) administration over a time frame of one minute at induction of anaesthesia Placebo given by single intravenous (IV) administration by slow push over one minute at induction of anaesthesia
All-Cause Mortality
APD421 5mg Dose Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/176 (0.00%)      0/166 (0.00%)    
Hide Serious Adverse Events
APD421 5mg Dose Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   8/176 (4.55%)      9/166 (5.42%)    
Cardiac disorders     
Acute Myocardial Infarction * 1  1/176 (0.57%)  1 0/166 (0.00%)  0
Supraventricular Tachycardia * 1  0/176 (0.00%)  0 1/166 (0.60%)  1
Gastrointestinal disorders     
Abdominal Distension * 1  0/176 (0.00%)  0 1/166 (0.60%)  1
Abdominal Pain * 1  0/176 (0.00%)  0 1/166 (0.60%)  1
Ileus * 1  1/176 (0.57%)  1 0/166 (0.00%)  0
Melaena * 1  0/176 (0.00%)  0 1/166 (0.60%)  1
Small Intestinal Obstruction * 1  1/176 (0.57%)  1 0/166 (0.00%)  0
Vomiting * 1  1/176 (0.57%)  1 1/166 (0.60%)  1
General disorders     
Pyrexia * 1  1/176 (0.57%)  1 0/166 (0.00%)  0
Infections and infestations     
Pneumonia * 1  0/176 (0.00%)  0 1/166 (0.60%)  1
Injury, poisoning and procedural complications     
Anaemia Postoperative * 1  1/176 (0.57%)  1 0/166 (0.00%)  0
Post Procedural Constipation * 1  0/176 (0.00%)  0 1/166 (0.60%)  1
Post Operative Ileus * 1  0/176 (0.00%)  0 2/166 (1.20%)  2
Metabolism and nutrition disorders     
Dehydration * 1  1/176 (0.57%)  1 0/166 (0.00%)  0
Renal and urinary disorders     
Haematuria * 1  1/176 (0.57%)  1 0/166 (0.00%)  0
1
Term from vocabulary, MedDRA Version 16.1
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5.0%
APD421 5mg Dose Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   169/176 (96.02%)      160/166 (96.39%)    
Blood and lymphatic system disorders     
Anaemia * 1  12/176 (6.82%)  12 9/166 (5.42%)  9
Gastrointestinal disorders     
Constipation * 1  12/176 (6.82%)  12 15/166 (9.04%)  15
Abdominal distension * 1  12/176 (6.82%)  12 9/166 (5.42%)  9
Injury, poisoning and procedural complications     
Anaemia Postoperative * 1  31/176 (17.61%)  31 32/166 (19.28%)  32
Procedural Pain * 1  42/176 (23.86%)  42 41/166 (24.70%)  41
Investigations     
Bood Prolactin Increased * 1  9/176 (5.11%)  9 1/166 (0.60%)  1
Metabolism and nutrition disorders     
Hyperglycaemia * 1  33/176 (18.75%)  33 38/166 (22.89%)  38
Hypocalcaemia * 1  26/176 (14.77%)  26 30/166 (18.07%)  30
Hypoalbuminaemia * 1  11/176 (6.25%)  11 11/166 (6.63%)  11
Hypoproteinaemia * 1  26/176 (14.77%)  26 25/166 (15.06%)  25
1
Term from vocabulary, MedDRA Version 16.1
*
Indicates events were collected by non-systematic assessment
There were no limitations and caveats in this study.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr Gabriel Fox
Organization: Acacia Pharma Ltd
Phone: 44-(0)1223-919764
EMail: Gabrielfox@acaciapharma.com
Layout table for additonal information
Responsible Party: Acacia Pharma Ltd
ClinicalTrials.gov Identifier: NCT01991860    
Other Study ID Numbers: DP10015
First Submitted: November 11, 2013
First Posted: November 25, 2013
Results First Submitted: August 7, 2018
Results First Posted: September 6, 2018
Last Update Posted: February 12, 2019