US Phase III Study of APD421 in PONV

• Sponsor: Acacia Pharma Ltd (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01991860
• Collaborator: (none)
• Enrollment: 364
• Location: 1
• Arms: 2
• Duration (Months): 5
• Patients Per Site Per Month: 72.4

Study Details

Study Description

Brief Summary

A comparison of the efficacy of APD421 and placebo in the prevention of PONV in patients at moderate-to-high risk of PONV.

Condition or Disease	Intervention/Treatment	Phase
PONV	Drug: APD421- Amisulpride for IV injection; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 364 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Randomized, Double-blind, Placebo-controlled Phase III Study of APD421 (Amisulpride for IV Injection) as Prophylaxis Against Post-operative Nausea and Vomiting
• Study Start Date: Aug 1, 2013
• Actual Primary Completion Date: Jan 1, 2014
• Actual Study Completion Date: Jan 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: APD421 APD421 (amisulpride), at 5mg given by single intravenous (IV) administration by slow push over one minute at induction of anaesthesia.	Drug: APD421- Amisulpride for IV injection; APD421 ( Amisulpride) at 5mg given by single intravenous (IV) administration, by slow push over one minute, at induction of anaesthesia; Other Names: Amisulpride for IV injection
Placebo Comparator: Placebo Matching placebo given by single IV administration by slow push over one minute at induction of anaesthesia	Drug: Placebo; Matching Placebo given by single intravenous (IV) administration, by slow push over one minute, at induction of anaesthesia

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Complete Response [24 hours after the end of surgery]

   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%.

Secondary Outcome Measures

1. Number of Participants With no Nausea. [24 hours after end of surgery]

   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.

2. Number of Participants With no Emesis [24 hours after end of surgery]

   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)

3. Number of Participants With no Use of Rescue Medication [24 hours after end of surgery]

   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.

4. The Number of Participants With no Emesis, no Significant Nausea and no Use of Rescue Medication [24 hours after the end of surgery]

   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.

5. The Number of Participants With no Significant Nausea [24 hours after the end of surgery]

   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.

6. Number of Participants With "Total Response" [24 hours after the end of surgery]

   Total response is defined as no occurrence of vomiting/retching, no nausea score ≥ 1 and no use of rescue medication.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female patients ≥ 18 years of age

• Patients undergoing elective surgery (open or laparoscopic technique) under general anaesthesia, expected to last at least one hour from induction of anaesthesia to wound closure and expected to require at least one overnight stay in hospital

Exclusion Criteria:

• Patients scheduled for outpatient/day case surgery

• Patients scheduled to undergo intra-thoracic, transplant or central nervous system surgery

• Patients scheduled to receive only a local anaesthetic/regional neuraxial (intrathecal or epidural) block

• Patients who are expected to remain ventilated for a period after surgery

• Patients who are expected to need a naso- or orogastric tube in situ after surgery is completed

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Duke	Durham	North Carolina	United States

Sponsors and Collaborators

• Acacia Pharma Ltd

Investigators

• Principal Investigator: Tong J Gan, MD, Duke University Medical College

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Acacia Pharma Ltd
• ClinicalTrials.gov Identifier: NCT01991860
• Other Study ID Numbers: DP10015
• First Posted: Nov 25, 2013
• Last Update Posted: Feb 12, 2019
• Last Verified: Jan 1, 2019

• Additional relevant MeSH terms: Amisulpride

Study Results

Participant Flow

Pre-assignment Detail	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
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

Baseline Characteristics

Arm/Group Title	5mg Dose APD421	Placebo	Total
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 Participants	176	166	342
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	54.5 (14.2)	53.0 (13.7)	53.8 (13.9)
Sex: Female, Male (Count of Participants)
Female	114 64.8%	110 66.3%	224 65.5%
Male	62 35.2%	56 33.7%	118 34.5%
Region of Enrollment (participants) [Number]
United States	176 100%	166 100%	342 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Complete Response
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	APD421 at 5mg	Placebo
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
Measure Participants	176	166
Count of Participants [Participants]	78 44.3%	54 32.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	APD421 at 5mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
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.
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	APD421 at 5mg	Placebo
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
Measure Participants	176	166
Count of Participants [Participants]	82 46.6%	64 38.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	APD421 at 5mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.16
	Comments
	Method	Chi-squared, Corrected
	Comments	Yates's continuity correction

3. Secondary Outcome

Title	Number of Participants With no Emesis
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	APD421 at 5mg	Placebo
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
Measure Participants	176	166
Count of Participants [Participants]	141 80.1%	129 77.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	APD421 at 5mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.68
	Comments
	Method	Chi-squared, Corrected
	Comments	Yates's continuity correction

4. Secondary Outcome

Title	Number of Participants With no Use of Rescue Medication
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	APD421 at 5mg	Placebo
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
Measure Participants	176	166
Count of Participants [Participants]	80 45.5%	55 33.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	APD421 at 5mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.026
	Comments
	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
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	APD421 at 5mg	Placebo
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
Measure Participants	176	166
Count of Participants [Participants]	73 41.5%	53 31.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	APD421 at 5mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.086
	Comments
	Method	Chi-squared, Corrected
	Comments	Yates's continuity correction

6. Secondary Outcome

Title	The Number of Participants With no Significant Nausea
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	APD421 at 5mg	Placebo
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
Measure Participants	176	166
Count of Participants [Participants]	107 60.8%	84 50.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	APD421 at 5mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.074
	Comments
	Method	Chi-squared, Corrected
	Comments	Yates's continuity correction

7. Secondary Outcome

Title	Number of Participants With "Total Response"
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	APD421 at 5mg	Placebo
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
Measure Participants	176	166
Count of Participants [Participants]	67 38.1%	50 30.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	APD421 at 5mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.15
	Comments
	Method	Chi-squared, Corrected
	Comments	Yates's continuity correction

Adverse Events

Time Frame	7 days
Arm/Group Title	APD421 5mg Dose		Placebo
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 (%)	# Events	Affected / at Risk (%)	# Events
Total	0/176 (0%)		0/166 (0%)
Serious Adverse Events
	APD421 5mg Dose		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/176 (4.5%)		9/166 (5.4%)
Cardiac disorders
Acute Myocardial Infarction	1/176 (0.6%)	1	0/166 (0%)	0
Supraventricular Tachycardia	0/176 (0%)	0	1/166 (0.6%)	1
Gastrointestinal disorders
Abdominal Distension	0/176 (0%)	0	1/166 (0.6%)	1
Abdominal Pain	0/176 (0%)	0	1/166 (0.6%)	1
Ileus	1/176 (0.6%)	1	0/166 (0%)	0
Melaena	0/176 (0%)	0	1/166 (0.6%)	1
Small Intestinal Obstruction	1/176 (0.6%)	1	0/166 (0%)	0
Vomiting	1/176 (0.6%)	1	1/166 (0.6%)	1
General disorders
Pyrexia	1/176 (0.6%)	1	0/166 (0%)	0
Infections and infestations
Pneumonia	0/176 (0%)	0	1/166 (0.6%)	1
Injury, poisoning and procedural complications
Anaemia Postoperative	1/176 (0.6%)	1	0/166 (0%)	0
Post Procedural Constipation	0/176 (0%)	0	1/166 (0.6%)	1
Post Operative Ileus	0/176 (0%)	0	2/166 (1.2%)	2
Metabolism and nutrition disorders
Dehydration	1/176 (0.6%)	1	0/166 (0%)	0
Renal and urinary disorders
Haematuria	1/176 (0.6%)	1	0/166 (0%)	0
Other (Not Including Serious) Adverse Events
	APD421 5mg Dose		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	169/176 (96%)		160/166 (96.4%)
Blood and lymphatic system disorders
Anaemia	12/176 (6.8%)	12	9/166 (5.4%)	9
Gastrointestinal disorders
Constipation	12/176 (6.8%)	12	15/166 (9%)	15
Abdominal distension	12/176 (6.8%)	12	9/166 (5.4%)	9
Injury, poisoning and procedural complications
Anaemia Postoperative	31/176 (17.6%)	31	32/166 (19.3%)	32
Procedural Pain	42/176 (23.9%)	42	41/166 (24.7%)	41
Investigations
Bood Prolactin Increased	9/176 (5.1%)	9	1/166 (0.6%)	1
Metabolism and nutrition disorders
Hyperglycaemia	33/176 (18.8%)	33	38/166 (22.9%)	38
Hypocalcaemia	26/176 (14.8%)	26	30/166 (18.1%)	30
Hypoalbuminaemia	11/176 (6.3%)	11	11/166 (6.6%)	11
Hypoproteinaemia	26/176 (14.8%)	26	25/166 (15.1%)	25

Limitations/Caveats

There were no limitations and caveats in this study.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.