Trial Outcomes & Findings for European Phase III Study of APD421 in PONV (NCT NCT01991821)

NCT ID: NCT01991821

Last Updated: 2019-08-20

Results Overview

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%.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 368 participants
• Primary outcome timeframe: 24 hours after end of surgery
• Results posted on: 2019-08-20

Participant Flow

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.

Participant milestones

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

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

European Phase III Study of APD421 in PONV

Baseline characteristics by cohort

Measure	APD421 n=169 Participants APD421 (amisulpride), at 5 mg given by single intravenous (IV) administration, by slow push over one to two minutes, at induction of anaesthesia.	Placebo n=178 Participants Matching placebo, given by single IV administration, by slow push over one minute at the induction of anaesthesia.	Total n=347 Participants Total of all reporting groups
Age, Continuous	51.7 Years STANDARD_DEVIATION 16.2 • n=5 Participants	51.6 Years STANDARD_DEVIATION 14.9 • n=7 Participants	51.6 Years STANDARD_DEVIATION 15.5 • n=5 Participants
Sex: Female, Male Female	147 Participants n=5 Participants	154 Participants n=7 Participants	301 Participants n=5 Participants
Sex: Female, Male Male	22 Participants n=5 Participants	24 Participants n=7 Participants	46 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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%.

Outcome measures

Measure	APD421 n=169 Participants APD421 (amisulpride), at 5 mg given by single intravenous (IV) administration, by slow push over one to two minutes, at induction of anaesthesia.	Placebo n=178 Participants Matching placebo, given by single IV administration, by slow push over one minute at the induction of anaesthesia.
Complete Response (no Emesis, Significant Nausea or Rescue Medication)	95 Participants	83 Participants

SECONDARY outcome

Timeframe: 24 hrs after end of surgery

Outcome measures

Measure	APD421 n=169 Participants APD421 (amisulpride), at 5 mg given by single intravenous (IV) administration, by slow push over one to two minutes, at induction of anaesthesia.	Placebo n=178 Participants Matching placebo, given by single IV administration, by slow push over one minute at the induction of anaesthesia.
Complete Response (no Emesis or Rescue Medication)	100 Participants	89 Participants

SECONDARY outcome

Timeframe: 24 hrs after end of surgery

Population: mITT

Outcome measures

Measure	APD421 n=169 Participants APD421 (amisulpride), at 5 mg given by single intravenous (IV) administration, by slow push over one to two minutes, at induction of anaesthesia.	Placebo n=178 Participants Matching placebo, given by single IV administration, by slow push over one minute at the induction of anaesthesia.
Total Response (no Emesis, Nausea or Rescue Medication)	87 Participants	73 Participants

SECONDARY outcome

Timeframe: 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

Outcome measures

Measure	APD421 n=169 Participants APD421 (amisulpride), at 5 mg given by single intravenous (IV) administration, by slow push over one to two minutes, at induction of anaesthesia.	Placebo n=178 Participants Matching placebo, given by single IV administration, by slow push over one minute at the induction of anaesthesia.
Incidence of Emesis (Vomiting/Retching)	34 Participants	46 Participants

SECONDARY outcome

Timeframe: 24 hours after end of surgery

Population: mITT

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

Outcome measures

Measure	APD421 n=169 Participants APD421 (amisulpride), at 5 mg given by single intravenous (IV) administration, by slow push over one to two minutes, at induction of anaesthesia.	Placebo n=178 Participants Matching placebo, given by single IV administration, by slow push over one minute at the induction of anaesthesia.
Incidence of Nausea	75 Participants	98 Participants

SECONDARY outcome

Timeframe: 24 hours after end of surgery

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

Outcome measures

Measure	APD421 n=169 Participants APD421 (amisulpride), at 5 mg given by single intravenous (IV) administration, by slow push over one to two minutes, at induction of anaesthesia.	Placebo n=178 Participants Matching placebo, given by single IV administration, by slow push over one minute at the induction of anaesthesia.
Incidence of Significant Nausea	63 Participants	84 Participants

SECONDARY outcome

Timeframe: 24 hours after end of surgery

Outcome measures

Measure	APD421 n=169 Participants APD421 (amisulpride), at 5 mg given by single intravenous (IV) administration, by slow push over one to two minutes, at induction of anaesthesia.	Placebo n=178 Participants Matching placebo, given by single IV administration, by slow push over one minute at the induction of anaesthesia.
Use of Rescue Medication	62 Participants	82 Participants

Adverse Events

APD421 at 5mg

Serious events: 3 serious events

Other events: 91 other events

Deaths: 0 deaths

Placebo

Serious events: 4 serious events

Other events: 178 other events

Deaths: 0 deaths

Serious adverse events

Measure	APD421 at 5mg n=169 participants at risk APD421 at 5mg given by single intravenous (IV) administration, by slow push over one to two minutes at induction of anaesthesia.	Placebo n=178 participants at risk APD421 Placebo given by single IV administration by slow push over one minute at induction of anaesthesia.
Injury, poisoning and procedural complications Anastomic Leak	0.59% 1/169 • Number of events 1 • 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	0.00% 0/178 • 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
Injury, poisoning and procedural complications Gastrointestinal Stoma Complication	0.00% 0/169 • 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	0.56% 1/178 • Number of events 1 • 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
Injury, poisoning and procedural complications Post Procedural Haemorrhage	0.00% 0/169 • 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	0.56% 1/178 • Number of events 1 • 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
Hepatobiliary disorders Portal Vein Thrombosis	0.59% 1/169 • Number of events 1 • 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	0.00% 0/178 • 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
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma	0.59% 1/169 • Number of events 1 • 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	0.00% 0/178 • 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
Nervous system disorders Presyncope	0.00% 0/169 • 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	0.56% 1/178 • Number of events 1 • 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
Vascular disorders Haemorrhage	0.00% 0/169 • 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	0.56% 1/178 • Number of events 1 • 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

Other adverse events

Measure	APD421 at 5mg n=169 participants at risk APD421 at 5mg given by single intravenous (IV) administration, by slow push over one to two minutes at induction of anaesthesia.	Placebo n=178 participants at risk APD421 Placebo given by single IV administration by slow push over one minute at induction of anaesthesia.
Injury, poisoning and procedural complications Procedural Pain	53.8% 91/169 • Number of events 91 • 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	51.7% 92/178 • Number of events 92 • 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
Gastrointestinal disorders Constipation	9.5% 16/169 • Number of events 16 • 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	5.1% 9/178 • Number of events 9 • 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
Gastrointestinal disorders Flatulence	10.7% 18/169 • Number of events 18 • 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	9.0% 16/178 • Number of events 16 • 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
Gastrointestinal disorders Nausea	11.8% 20/169 • Number of events 20 • 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	10.1% 18/178 • Number of events 18 • 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
Investigations Blood Prolactin Increased	10.7% 18/169 • Number of events 18 • 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	1.1% 2/178 • Number of events 2 • 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
Vascular disorders Hypotension	5.3% 9/169 • Number of events 9 • 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	7.9% 14/178 • Number of events 14 • 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
Nervous system disorders Headache	8.3% 14/169 • Number of events 14 • 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	5.1% 9/178 • Number of events 9 • 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
Psychiatric disorders Sleep Disorder	4.1% 7/169 • Number of events 7 • 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	5.1% 9/178 • Number of events 9 • 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
Blood and lymphatic system disorders Anaemia	5.9% 10/169 • Number of events 10 • 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	5.1% 9/178 • Number of events 9 • 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

Additional Information

Dr Gabriel Fox

Acacia Pharma

Phone: 01223875130

Email: GabrielFox@acaciapharma.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: GT60