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Phase IIIb Study of APD421 in Combination as PONV Prophylaxis

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: NCT02337062
Recruitment Status : Completed
First Posted : January 13, 2015
Results First Posted : August 4, 2017
Last Update Posted : March 20, 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
Drug: Placebo
Enrollment 1147
Recruitment Details

Study start date:- 12th February 2015 (first patient in)

Study completion date:- 28th September 2015 (last patient last visit)

Location:-France, Germany and the USA.
Pre-assignment Details  
Arm/Group Title APD421 + Standard Anti-emetic Placebo + Standard Anti-emetic
Hide Arm/Group Description APD421 (amisulpride) at 5 mg administered as a single, slow, intravenous (IV) push over one minute at the time of induction of anaesthesia; given in combination with standard anti-emetic. Matching Placebo administered as a single, slow push, IV push over one minute at the time of induction anaesthesia given in combination with standard anti-emetic
Period Title: Overall Study
Started 572 575
Completed 555 556
Not Completed 17 19
Arm/Group Title APD421 + Standard Anti-emetic Placebo + Standard Anti-emetic Total
Hide Arm/Group Description

Single dose of IV APD421

APD421

Single dose of IV placebo

Placebo

 Total of all reporting groups
Overall Number of Baseline Participants 572 575 1147
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 572 participants 575 participants 1147 participants
48.8  (14.24) 48.3  (13.98) 48.5  (14.10)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 572 participants 575 participants 1147 participants
Female
552
  96.5%
557
  96.9%
1109
  96.7%
Male
20
   3.5%
18
   3.1%
38
   3.3%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
 Number Analyzed 572 participants 575 participants 1147 participants
United States
353
  61.7%
351
  61.0%
704
  61.4%
France
79
  13.8%
85
  14.8%
164
  14.3%
Germany
140
  24.5%
139
  24.2%
279
  24.3%
1.Primary Outcome
Title Number of Participants With Complete Response
Hide Description Complete response defined as no emesis and no use of rescue medication in the 24 hour period after end of surgery (defined as wound closure)
Time Frame 24 hours after the end of surgery
Hide Outcome Measure Data
Hide Analysis Population Description
Modified intent-to-treat
Arm/Group Title APD421 5mg + Standard Anti-emetic Placebo + Standard Anti-emetic
Hide Arm/Group Description:
APD421 (amisulpride) at 5 mg administered as a single, slow, intravenous (IV) push over one minute at the time of induction of anaesthesia; given in combination with standard anti-emetic.
Matching placebo administered as a single, slow, IV push over one minute, at the time of induction of anaesthesia; given in combination with standard anti-emetic
Overall Number of Participants Analyzed 572 575
Measure Type: Count of Participants
Unit of Measure: Participants
330
  57.7%
268
  46.6%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection APD421 5mg + Standard Anti-emetic, Placebo + Standard Anti-emetic
Comments The primary efficacy analysis was a comparison of the incidence of the primary efficacy variable between the two groups that received APD421 and the group that received placebo, using Pearson's χ2 test.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments The threshold for determining statistical significance in the comparison of incidence of success between the active and placebo groups (the primary efficacy analysis) was a p-value of 2.5% one-sided.
Method Chi-squared
Comments [Not Specified]
2.Secondary Outcome
Title Number of Participants With 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 the end of surgery
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title APD421 5mg + Standard Anti-emetic Placebo + Standard Anti-emetic
Hide Arm/Group Description:
Single IV dose of 5 mg APD421 administered in combination with standard anti-emetic
Single dose of IV placebo administered in combination with standard anti-emetic
Overall Number of Participants Analyzed 572 575
Measure Type: Count of Participants
Unit of Measure: Participants
79
  13.8%
115
  20.0%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection APD421 5mg + Standard Anti-emetic, Placebo + Standard Anti-emetic
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
3.Secondary Outcome
Title Number of Participants Receiving Rescue Medication
Hide Description Rescue medication defined as an antiemetic (or other medication) given with the intention of relieving nausea and/or emesis, or any incidental use of a drug known to have antiemetic potential
Time Frame 24 hours after the end of surgery
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title APD421 5mg + Standard Anti-emetic Placebo + Standard Anti-emetic
Hide Arm/Group Description:
Single IV dose of 5 mg APD421 administered in combination with standard anti-emetic
Single dose of IV placebo administered in combination with standard anti-emetic
Overall Number of Participants Analyzed 572 575
Measure Type: Count of Participants
Unit of Measure: Participants
234
  40.9%
284
  49.4%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection APD421 5mg + Standard Anti-emetic, Placebo + Standard Anti-emetic
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
4.Secondary Outcome
Title Number of Participants With Any 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. "Any nausea" means a score ≥ 1.
Time Frame 24 hours after the end of surgery
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title APD421 5mg + Standard Anti-emetic Placebo + Standard Anti-emetic
Hide Arm/Group Description:
Single IV dose of 5 mg APD421 administered in combination with standard anti-emetic
Single dose of IV placebo administered in combination with standard anti-emetic
Overall Number of Participants Analyzed 572 575
Measure Type: Count of Participants
Unit of Measure: Participants
286
  50.0%
335
  58.3%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection APD421 5mg + Standard Anti-emetic, Placebo + Standard Anti-emetic
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
5.Secondary Outcome
Title Number of Participants With 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. "Significant nausea" means a score ≥ 4.
Time Frame 24 hours after end of surgery
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title APD421 5mg + Standard Anti-emetic Placebo + Standard Anti-emetic
Hide Arm/Group Description:
Single IV dose of 5 mg APD421 administered in combination with standard anti-emetic
Single dose of IV placebo administered in combination with standard anti-emetic
Overall Number of Participants Analyzed 572 575
Measure Type: Count of Participants
Unit of Measure: Participants
212
  37.1%
274
  47.7%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection APD421 5mg + Standard Anti-emetic, Placebo + Standard Anti-emetic
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
6.Secondary Outcome
Title Time to First Violation of Criteria for PONV
Hide Description Criteria for PONV are any episode of emesis or use of rescue medication in the 24 hours after the end of surgery
Time Frame 24 hours after end of surgery
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title APD421 5mg + Standard Anti-emetic Placebo + Standard Anti-emetic
Hide Arm/Group Description:
APD421 (amisulpride) at 5 mg administered as a single, slow, intravenous (IV) push over one minute at the time of induction of anaesthesia; given in combination with standard anti-emetic.
Matching placebo administered as a single, slow, IV push over one minute, at the time of induction of anaesthesia; given in combination with standard anti-emetic
Overall Number of Participants Analyzed 572 575
Median (Inter-Quartile Range)
Unit of Measure: minutes
NA [1] 
(195.5 to NA)
821.0 [2] 
(107.0 to NA)
[1]
Median value not available as <50% of participants met criteria for PONV. Upper bound of IQR not available as <75% of participants met criteria for PONV.
[2]
Upper bound of IQR not available as <75% of participants met criteria for PONV.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection APD421 5mg + Standard Anti-emetic, Placebo + Standard Anti-emetic
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Time Frame For the 7 day period after study drug administration
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title APD421 + Standard Anti-emetic Placebo + Standard Anti-emetic
Hide Arm/Group Description

Single dose of IV APD421

APD421

Single dose of IV placebo

Placebo
All-Cause Mortality
APD421 + Standard Anti-emetic Placebo + Standard Anti-emetic
Affected / at Risk (%) Affected / at Risk (%)
Total   1/572 (0.17%)      0/575 (0.00%)    
Hide Serious Adverse Events
APD421 + Standard Anti-emetic Placebo + Standard Anti-emetic
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   14/572 (2.45%)      14/575 (2.43%)    
Gastrointestinal disorders     
Small intestinal Obstruction * 1  1/572 (0.17%)  1 2/575 (0.35%)  2
Intra-abdominal haemorrhage * 1  1/572 (0.17%)  1 0/575 (0.00%)  0
Nausea * 1  0/572 (0.00%)  0 1/575 (0.17%)  1
Vomiting * 1  0/572 (0.00%)  0 1/575 (0.17%)  1
Infections and infestations     
Peritonitis * 1  2/572 (0.35%)  2 0/575 (0.00%)  0
Pneumonia * 1  1/572 (0.17%)  1 1/575 (0.17%)  1
Post Operative wound infections * 1  2/572 (0.35%)  2 0/575 (0.00%)  0
Gastroenteritis viral * 1  1/572 (0.17%)  1 0/575 (0.00%)  0
Sepsis * 1  1/572 (0.17%)  1 0/575 (0.00%)  0
Staphylococcal infections * 1  0/572 (0.00%)  0 1/575 (0.17%)  1
Urinary Tract Infection * 1  0/572 (0.00%)  0 1/575 (0.17%)  1
Wound infection * 1  0/572 (0.00%)  0 1/575 (0.17%)  1
Injury, poisoning and procedural complications     
Post Procedural haemorrhage * 1  2/572 (0.35%)  2 2/575 (0.35%)  2
Wound Secretion * 1  1/572 (0.17%)  1 1/575 (0.17%)  1
Herpatic Haematoma * 1  0/572 (0.00%)  0 1/575 (0.17%)  1
Pelvic Organ Injury * 1  1/572 (0.17%)  1 0/575 (0.00%)  0
Postoerative ileus * 1  0/572 (0.00%)  0 1/575 (0.17%)  1
Procedural Haemorrhage * 1  0/572 (0.00%)  0 1/575 (0.17%)  1
Procedural Pain * 1  1/572 (0.17%)  1 0/575 (0.00%)  0
1
Term from vocabulary, MedDRA 17.1
*
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 + Standard Anti-emetic Placebo + Standard Anti-emetic
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   111/572 (19.41%)      120/575 (20.87%)    
Gastrointestinal disorders     
Nausea * 1  62/572 (10.84%)  62 70/575 (12.17%)  70
Injury, poisoning and procedural complications     
Procedural Pain * 1  53/572 (9.27%)  53 58/575 (10.09%)  58
1
Term from vocabulary, MedDRA 17.1
*
Indicates events were collected by non-systematic assessment
There were no limitations and caveats that occurred during the duration of 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: NCT02337062    
Other Study ID Numbers: DP10017
First Submitted: January 9, 2015
First Posted: January 13, 2015
Results First Submitted: July 7, 2017
Results First Posted: August 4, 2017
Last Update Posted: March 20, 2019