European Phase III Study of APD421 in PONV

• Sponsor: Acacia Pharma Ltd (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01991821
• Collaborator: (none)
• Enrollment: 368
• Locations: 2
• Arms: 2
• Duration (Months): 6
• Patients Per Site: 184
• Patients Per Site Per Month: 30.4

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; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 368 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Randomised, Double-blind, Placebo-controlled Phase III Study of APD421 (Amisulpride for IV Injection) as Prophylaxis Against Post-operative Nausea and Vomiting
• Study Start Date: Jul 1, 2013
• Actual Primary Completion Date: Jan 1, 2014
• Actual Study Completion Date: Jan 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: APD421 IV APD421 single dose	Drug: APD421
Placebo Comparator: Placebo IV placebo single dose	Drug: Placebo

Outcome Measures

Primary Outcome Measures

1. Complete Response (no Emesis, Significant Nausea or Rescue Medication) [24 hours after end of surgery]

   The primary efficacy analysis was a comparison of the incidence of Complete Response (absence of PONV1) in the 0-24-hour period after surgery, between the active treatment group and the placebo group using Pearson square test with Yates's continuity correction at a two-sided significance level of 5%.

Secondary Outcome Measures

1. Complete Response (no Emesis or Rescue Medication) [24 hrs after end of surgery]

2. Total Response (no Emesis, Nausea or Rescue Medication) [24 hrs after end of surgery]

3. Incidence of Emesis (Vomiting/Retching) [24 hours after end of surgeryry]

   An assessment of a participant experiencing an episode of emesis (vomiting/ retching) or received anti-emetic rescue medication during the 24hours after the completion of the surgery

4. Incidence of Nausea [24 hours after end of surgery]

   Count of patients experiencing an episode of nausea scored ≥ 1 of 0-10 verbal response scale during the 24 hours period after the completion of surgery

5. Incidence of Significant Nausea [24 hours after end of surgery]

   Count of participants with nausea score ≥ 4 on 0-10 verbal response scale

6. Use of Rescue Medication [24 hours after end of surgery]

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	CHU de Hautepierre	Strasbourg		France
2	University Hospitals of Würzburg	Würzburg		Germany

Sponsors and Collaborators

• Acacia Pharma Ltd

Investigators

• Principal Investigator: Pierre Diemunsch, MD, Hôpital de Hautepierre

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Acacia Pharma Ltd
• ClinicalTrials.gov Identifier: NCT01991821
• Other Study ID Numbers: DP10014
• First Posted: Nov 25, 2013
• Last Update Posted: Aug 20, 2019
• Last Verified: Aug 1, 2019

Study Results

Participant Flow

Pre-assignment Detail	Of the 368 patients enrolled in the study, 21 patients were not randomised and not dosed. Of these, 3 withdrew their consent, 5 did not comply with the protocol procedures and 13 were not dosed for other unspecified reasons.

Arm/Group Title	APD421	Placebo
Arm/Group Description	APD421 (amisulpride), at 5 mg given by single intravenous (IV) administration, by slow push over one to two minutes, at induction of anaesthesia.	Matching placebo, given by single IV administration, by slow push over one minute at the induction of anaesthesia.
Period Title: Overall Study
STARTED	169	178
COMPLETED	6	11
NOT COMPLETED	163	167

Baseline Characteristics

Arm/Group Title	APD421	Placebo	Total
Arm/Group Description	APD421 (amisulpride), at 5 mg given by single intravenous (IV) administration, by slow push over one to two minutes, at induction of anaesthesia.	Matching placebo, given by single IV administration, by slow push over one minute at the induction of anaesthesia.	Total of all reporting groups
Overall Participants	169	178	347
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	51.7 (16.2)	51.6 (14.9)	51.6 (15.5)
Sex: Female, Male (Count of Participants)
Female	147 87%	154 86.5%	301 86.7%
Male	22 13%	24 13.5%	46 13.3%

Outcome Measures

1. Primary Outcome

Title	Complete Response (no Emesis, Significant Nausea or Rescue Medication)
Description	The primary efficacy analysis was a comparison of the incidence of Complete Response (absence of PONV1) in the 0-24-hour period after surgery, between the active treatment group and the placebo group using Pearson square test with Yates's continuity correction at a two-sided significance level of 5%.
Time Frame	24 hours after end of surgery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	APD421	Placebo
Arm/Group Description	APD421 (amisulpride), at 5 mg given by single intravenous (IV) administration, by slow push over one to two minutes, at induction of anaesthesia.	Matching placebo, given by single IV administration, by slow push over one minute at the induction of anaesthesia.
Measure Participants	169	178
Count of Participants [Participants]	95 56.2%	83 46.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	APD421, Placebo
	Comments	The primary efficacy analysis was a complete response which is defined as protection from PONV1, which was absence of any episode of emesis, significant nausea or use of rescue medication with the first 24 hours post-operatively.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.093
	Comments	The complete response of the primary efficacy analysis occurred in 95 patients (56.2%; 95% confidence interval [CI] 48.4 - 63.8%) in the APD421 group and 83 patients (46.6%; 95% CI 39.1- 54.2%) in the placebo group
	Method	Chi-squared, Corrected
	Comments	Pearson square test with Yates's continuity correction and with the two- sided significance level of 5%

2. Secondary Outcome

Title	Complete Response (no Emesis or Rescue Medication)
Time Frame	24 hrs after end of surgery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	APD421	Placebo
Arm/Group Description	APD421 (amisulpride), at 5 mg given by single intravenous (IV) administration, by slow push over one to two minutes, at induction of anaesthesia.	Matching placebo, given by single IV administration, by slow push over one minute at the induction of anaesthesia.
Measure Participants	169	178
Count of Participants [Participants]	100 59.2%	89 50%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	APD421, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.059
	Comments	Two-sided, significance threshold = 0.05
	Method	Chi-squared, Corrected
	Comments

3. Secondary Outcome

Title	Total Response (no Emesis, Nausea or Rescue Medication)
Time Frame	24 hrs after end of surgery

Outcome Measure Data

Analysis Population Description

mITT

Arm/Group Title	APD421	Placebo
Arm/Group Description	APD421 (amisulpride), at 5 mg given by single intravenous (IV) administration, by slow push over one to two minutes, at induction of anaesthesia.	Matching placebo, given by single IV administration, by slow push over one minute at the induction of anaesthesia.
Measure Participants	169	178
Count of Participants [Participants]	87 51.5%	73 41%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	APD421, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.053
	Comments	Two-sided, significance threshold = 0.05
	Method	Chi-squared, Corrected
	Comments

4. Secondary Outcome

Title	Incidence of Emesis (Vomiting/Retching)
Description	An assessment of a participant experiencing an episode of emesis (vomiting/ retching) or received anti-emetic rescue medication during the 24hours after the completion of the surgery
Time Frame	24 hours after end of surgeryry

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	APD421 at 5mg	Placebo
Arm/Group Description	IV 5mg APD421 single dose	IV placebo single dose Placebo
Measure Participants	169	178
Count of Participants [Participants]	34 20.1%	46 25.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	APD421, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.26
	Comments	Two-sided, significance threshold = 0.05
	Method	Chi-squared, Corrected
	Comments

5. Secondary Outcome

Title	Incidence of Nausea
Description	Count of patients experiencing an episode of nausea scored ≥ 1 of 0-10 verbal response scale during the 24 hours period after the completion of surgery
Time Frame	24 hours after end of surgery

Outcome Measure Data

Analysis Population Description

mITT

Arm/Group Title	APD421 at 5mg	Placebo
Arm/Group Description	IV 5mg APD421 single dose	IV placebo single dose Placebo
Measure Participants	169	178
Count of Participants [Participants]	75 44.4%	98 55.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	APD421, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.06
	Comments	Two-sided, significance threshold = 0.05
	Method	Chi-squared, Corrected
	Comments

6. Secondary Outcome

Title	Incidence of Significant Nausea
Description	Count of participants with nausea score ≥ 4 on 0-10 verbal response scale
Time Frame	24 hours after end of surgery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	APD421	Placebo
Arm/Group Description	APD421 (amisulpride), at 5 mg given by single intravenous (IV) administration, by slow push over one to two minutes, at induction of anaesthesia.	Matching placebo, given by single IV administration, by slow push over one minute at the induction of anaesthesia.
Measure Participants	169	178
Count of Participants [Participants]	63 37.3%	84 47.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	APD421, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.079
	Comments	Two-sided, significance threshold = 0.05
	Method	Chi-squared, Corrected
	Comments

7. Secondary Outcome

Title	Use of Rescue Medication
Time Frame	24 hours after end of surgery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	APD421	Placebo
Arm/Group Description	APD421 (amisulpride), at 5 mg given by single intravenous (IV) administration, by slow push over one to two minutes, at induction of anaesthesia.	Matching placebo, given by single IV administration, by slow push over one minute at the induction of anaesthesia.
Measure Participants	169	178
Count of Participants [Participants]	62 36.7%	82 46.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	APD421, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.096
	Comments
	Method	Chi-squared, Corrected
	Comments

Adverse Events

Time Frame	Any AE that is serious occurring during the course of the study, irrespective of the treatment received by the subject must be reported to the pharmacovigilance provider within 24hours of it's recognition
Arm/Group Title	APD421 at 5mg		Placebo
Arm/Group Description	APD421 at 5mg given by single intravenous (IV) administration, by slow push over one to two minutes at induction of anaesthesia.		APD421 Placebo given by single IV administration by slow push over one minute at induction of anaesthesia.
All Cause Mortality
	APD421 at 5mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/169 (0%)		0/178 (0%)
Serious Adverse Events
	APD421 at 5mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/169 (1.8%)		4/178 (2.2%)
Hepatobiliary disorders
Portal Vein Thrombosis	1/169 (0.6%)	1	0/178 (0%)	0
Injury, poisoning and procedural complications
Anastomic Leak	1/169 (0.6%)	1	0/178 (0%)	0
Gastrointestinal Stoma Complication	0/169 (0%)	0	1/178 (0.6%)	1
Post Procedural Haemorrhage	0/169 (0%)	0	1/178 (0.6%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma	1/169 (0.6%)	1	0/178 (0%)	0
Nervous system disorders
Presyncope	0/169 (0%)	0	1/178 (0.6%)	1
Vascular disorders
Haemorrhage	0/169 (0%)	0	1/178 (0.6%)	1
Other (Not Including Serious) Adverse Events
	APD421 at 5mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	91/169 (53.8%)		178/178 (100%)
Blood and lymphatic system disorders
Anaemia	10/169 (5.9%)	10	9/178 (5.1%)	9
Gastrointestinal disorders
Constipation	16/169 (9.5%)	16	9/178 (5.1%)	9
Flatulence	18/169 (10.7%)	18	16/178 (9%)	16
Nausea	20/169 (11.8%)	20	18/178 (10.1%)	18
Injury, poisoning and procedural complications
Procedural Pain	91/169 (53.8%)	91	92/178 (51.7%)	92
Investigations
Blood Prolactin Increased	18/169 (10.7%)	18	2/178 (1.1%)	2
Nervous system disorders
Headache	14/169 (8.3%)	14	9/178 (5.1%)	9
Psychiatric disorders
Sleep Disorder	7/169 (4.1%)	7	9/178 (5.1%)	9
Vascular disorders
Hypotension	9/169 (5.3%)	9	14/178 (7.9%)	14

Limitations/Caveats

There are no limitations and caveats with 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.