Trial Outcomes & Findings for US Phase III Study of APD421 in PONV (NCT NCT01991860)

NCT ID: NCT01991860

Last Updated: 2019-02-12

Results Overview

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%.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

364 participants

Primary outcome timeframe

24 hours after the end of surgery

Results posted on

2019-02-12

Participant Flow

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.

Participant milestones

Participant milestones
Measure	5mg APD421 A 5mg (2mL) dose of APD421 given by slow intravenous (IV) push over one minute at induction of anaesthesia	Placebo 2mL of placebo given by slow intravenous (IV) push over one minute at induction of anaesthesia
Overall Study STARTED	176	166
Overall Study COMPLETED	172	164
Overall Study NOT COMPLETED	4	2

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

US Phase III Study of APD421 in PONV

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	5mg Dose APD421 n=176 Participants 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 n=166 Participants Single dose placebo given through intravenous (IV) administration	Total n=342 Participants Total of all reporting groups
Age, Continuous	54.5 Years STANDARD_DEVIATION 14.2 • n=5 Participants	53.0 Years STANDARD_DEVIATION 13.7 • n=7 Participants	53.8 Years STANDARD_DEVIATION 13.9 • n=5 Participants
Sex: Female, Male Female	114 Participants n=5 Participants	110 Participants n=7 Participants	224 Participants n=5 Participants
Sex: Female, Male Male	62 Participants n=5 Participants	56 Participants n=7 Participants	118 Participants n=5 Participants
Region of Enrollment United States	176 participants n=5 Participants	166 participants n=7 Participants	342 participants n=5 Participants

PRIMARY outcome

Timeframe: 24 hours after the end of surgery

Outcome measures

Outcome measures
Measure	APD421 at 5mg n=176 Participants A 5mg (2mL) dose of APD421 given by slow intravenous (IV) push over one minute at induction of anaesthesia	Placebo n=166 Participants A 2mL dose of placebo given by slow intravenous (IV) push over one minute at induction of anaesthesia
Number of Participants With Complete Response	78 Participants	54 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	APD421 at 5mg n=176 Participants A 5mg (2mL) dose of APD421 given by slow intravenous (IV) push over one minute at induction of anaesthesia	Placebo n=166 Participants A 2mL dose of placebo given by slow intravenous (IV) push over one minute at induction of anaesthesia
Number of Participants With no Nausea.	82 Participants	64 Participants

SECONDARY outcome

Timeframe: 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)

Outcome measures

Outcome measures
Measure	APD421 at 5mg n=176 Participants A 5mg (2mL) dose of APD421 given by slow intravenous (IV) push over one minute at induction of anaesthesia	Placebo n=166 Participants A 2mL dose of placebo given by slow intravenous (IV) push over one minute at induction of anaesthesia
Number of Participants With no Emesis	141 Participants	129 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	APD421 at 5mg n=176 Participants A 5mg (2mL) dose of APD421 given by slow intravenous (IV) push over one minute at induction of anaesthesia	Placebo n=166 Participants A 2mL dose of placebo given by slow intravenous (IV) push over one minute at induction of anaesthesia
Number of Participants With no Use of Rescue Medication	80 Participants	55 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	APD421 at 5mg n=176 Participants A 5mg (2mL) dose of APD421 given by slow intravenous (IV) push over one minute at induction of anaesthesia	Placebo n=166 Participants A 2mL dose of placebo given by slow intravenous (IV) push over one minute at induction of anaesthesia
The Number of Participants With no Emesis, no Significant Nausea and no Use of Rescue Medication	73 Participants	53 Participants

SECONDARY outcome

Timeframe: 24 hours after the end of surgery

Outcome measures

Outcome measures
Measure	APD421 at 5mg n=176 Participants A 5mg (2mL) dose of APD421 given by slow intravenous (IV) push over one minute at induction of anaesthesia	Placebo n=166 Participants A 2mL dose of placebo given by slow intravenous (IV) push over one minute at induction of anaesthesia
The Number of Participants With no Significant Nausea	107 Participants	84 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	APD421 at 5mg n=176 Participants A 5mg (2mL) dose of APD421 given by slow intravenous (IV) push over one minute at induction of anaesthesia	Placebo n=166 Participants A 2mL dose of placebo given by slow intravenous (IV) push over one minute at induction of anaesthesia
Number of Participants With "Total Response"	67 Participants	50 Participants

Adverse Events

APD421 5mg Dose

Serious events: 8 serious events

Other events: 169 other events

Deaths: 0 deaths

Placebo

Serious events: 9 serious events

Other events: 160 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	APD421 5mg Dose n=176 participants at risk 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 n=166 participants at risk Placebo given by single intravenous (IV) administration by slow push over one minute at induction of anaesthesia
Gastrointestinal disorders Abdominal Distension	0.00% 0/176 • 7 days	0.60% 1/166 • Number of events 1 • 7 days
Gastrointestinal disorders Abdominal Pain	0.00% 0/176 • 7 days	0.60% 1/166 • Number of events 1 • 7 days
Gastrointestinal disorders Ileus	0.57% 1/176 • Number of events 1 • 7 days	0.00% 0/166 • 7 days
Gastrointestinal disorders Melaena	0.00% 0/176 • 7 days	0.60% 1/166 • Number of events 1 • 7 days
Gastrointestinal disorders Small Intestinal Obstruction	0.57% 1/176 • Number of events 1 • 7 days	0.00% 0/166 • 7 days
Gastrointestinal disorders Vomiting	0.57% 1/176 • Number of events 1 • 7 days	0.60% 1/166 • Number of events 1 • 7 days
Injury, poisoning and procedural complications Anaemia Postoperative	0.57% 1/176 • Number of events 1 • 7 days	0.00% 0/166 • 7 days
Injury, poisoning and procedural complications Post Procedural Constipation	0.00% 0/176 • 7 days	0.60% 1/166 • Number of events 1 • 7 days
Injury, poisoning and procedural complications Post Operative Ileus	0.00% 0/176 • 7 days	1.2% 2/166 • Number of events 2 • 7 days
Cardiac disorders Acute Myocardial Infarction	0.57% 1/176 • Number of events 1 • 7 days	0.00% 0/166 • 7 days
Cardiac disorders Supraventricular Tachycardia	0.00% 0/176 • 7 days	0.60% 1/166 • Number of events 1 • 7 days
General disorders Pyrexia	0.57% 1/176 • Number of events 1 • 7 days	0.00% 0/166 • 7 days
Infections and infestations Pneumonia	0.00% 0/176 • 7 days	0.60% 1/166 • Number of events 1 • 7 days
Metabolism and nutrition disorders Dehydration	0.57% 1/176 • Number of events 1 • 7 days	0.00% 0/166 • 7 days
Renal and urinary disorders Haematuria	0.57% 1/176 • Number of events 1 • 7 days	0.00% 0/166 • 7 days

Other adverse events

Other adverse events
Measure	APD421 5mg Dose n=176 participants at risk 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 n=166 participants at risk Placebo given by single intravenous (IV) administration by slow push over one minute at induction of anaesthesia
Injury, poisoning and procedural complications Anaemia Postoperative	17.6% 31/176 • Number of events 31 • 7 days	19.3% 32/166 • Number of events 32 • 7 days
Injury, poisoning and procedural complications Procedural Pain	23.9% 42/176 • Number of events 42 • 7 days	24.7% 41/166 • Number of events 41 • 7 days
Metabolism and nutrition disorders Hyperglycaemia	18.8% 33/176 • Number of events 33 • 7 days	22.9% 38/166 • Number of events 38 • 7 days
Metabolism and nutrition disorders Hypocalcaemia	14.8% 26/176 • Number of events 26 • 7 days	18.1% 30/166 • Number of events 30 • 7 days
Metabolism and nutrition disorders Hypoalbuminaemia	6.2% 11/176 • Number of events 11 • 7 days	6.6% 11/166 • Number of events 11 • 7 days
Metabolism and nutrition disorders Hypoproteinaemia	14.8% 26/176 • Number of events 26 • 7 days	15.1% 25/166 • Number of events 25 • 7 days
Gastrointestinal disorders Constipation	6.8% 12/176 • Number of events 12 • 7 days	9.0% 15/166 • Number of events 15 • 7 days
Gastrointestinal disorders Abdominal distension	6.8% 12/176 • Number of events 12 • 7 days	5.4% 9/166 • Number of events 9 • 7 days
Investigations Bood Prolactin Increased	5.1% 9/176 • Number of events 9 • 7 days	0.60% 1/166 • Number of events 1 • 7 days
Blood and lymphatic system disorders Anaemia	6.8% 12/176 • Number of events 12 • 7 days	5.4% 9/166 • Number of events 9 • 7 days

Additional Information

Dr Gabriel Fox

Acacia Pharma Ltd

Phone: 44-(0)1223-919764

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60