Trial Outcomes & Findings for Study of APD421 as PONV Treatment (Prior Prophylaxis) (NCT NCT02646566)

NCT ID: NCT02646566

Last Updated: 2019-01-22

Results Overview

The primary efficacy variable was the dichotomous variable: success or failure of initial PONV treatment, where success is defined as no emetic episodes (vomiting or retching) from 30 minutes\* to 24 hours after administration of study medication and no administration of anti-emetic rescue medication at any time in the 24-hour period after administration of study medication.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 705 participants
• Primary outcome timeframe: 0-24 hours after administration of study medication
• Results posted on: 2019-01-22

Participant Flow

Estimated recruitment was 700, to deliver 690 evaluable, randomised patients, providing an average of 230 evaluable patients in each of the three groups. The number of randomised patients planned per country was as follows: Germany, 190; France, 15; Canada, 100; and USA, 395

Three patients were randomised but not dosed: 2 due to withdrawal of consent, 1 for other reasons.

Participant milestones

Measure	APD421 5mg APD421 5mg administered as a single, slow intravenous (IV) push over about two minutes	APD421 10mg APD421 10mg administered as a single,slow intravenous (IV) push over about two minutes	Placebo Matching Placebo administered as a single, slow intravenous (IV) push over about two minutes
Overall Study STARTED	237	230	235
Overall Study COMPLETED	231	226	230
Overall Study NOT COMPLETED	6	4	5

Reasons for withdrawal

Measure	APD421 5mg APD421 5mg administered as a single, slow intravenous (IV) push over about two minutes	APD421 10mg APD421 10mg administered as a single,slow intravenous (IV) push over about two minutes	Placebo Matching Placebo administered as a single, slow intravenous (IV) push over about two minutes
Overall Study Lost to Follow-up	5	4	5
Overall Study Treatment failure	1	0	0

Baseline Characteristics

Study of APD421 as PONV Treatment (Prior Prophylaxis)

Baseline characteristics by cohort

Measure	APD421 5mg n=237 Participants APD421 5mg administered as a single, slow intravenous (IV) push over about two minutes	APD421 10mg n=230 Participants APD421 10mg administered as a single, slow intravenous (IV) push over about two minutes	Placebo n=235 Participants Matching placebo administered as a single, slow, IV push over about two minutes	Total n=702 Participants Total of all reporting groups
Age, Categorical <=18 years	1 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	214 Participants n=5 Participants	204 Participants n=7 Participants	216 Participants n=5 Participants	634 Participants n=4 Participants
Age, Categorical >=65 years	22 Participants n=5 Participants	24 Participants n=7 Participants	18 Participants n=5 Participants	64 Participants n=4 Participants
Age, Continuous	45.8 Years STANDARD_DEVIATION 13.12 • n=5 Participants	46.9 Years STANDARD_DEVIATION 13.03 • n=7 Participants	46.0 Years STANDARD_DEVIATION 13.38 • n=5 Participants	46.3 Years STANDARD_DEVIATION 13.17 • n=4 Participants
Sex: Female, Male Female	213 Participants n=5 Participants	208 Participants n=7 Participants	212 Participants n=5 Participants	633 Participants n=4 Participants
Sex: Female, Male Male	24 Participants n=5 Participants	22 Participants n=7 Participants	23 Participants n=5 Participants	69 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Asian	5 Participants n=5 Participants	6 Participants n=7 Participants	8 Participants n=5 Participants	19 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Black or African American	19 Participants n=5 Participants	21 Participants n=7 Participants	22 Participants n=5 Participants	62 Participants n=4 Participants
Race (NIH/OMB) White	196 Participants n=5 Participants	189 Participants n=7 Participants	193 Participants n=5 Participants	578 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	15 Participants n=5 Participants	14 Participants n=7 Participants	12 Participants n=5 Participants	41 Participants n=4 Participants

PRIMARY outcome

Timeframe: 0-24 hours after administration of study medication

Population: Modified ITT population

The primary efficacy variable was the dichotomous variable: success or failure of initial PONV treatment, where success is defined as no emetic episodes (vomiting or retching) from 30 minutes* to 24 hours after administration of study medication and no administration of anti-emetic rescue medication at any time in the 24-hour period after administration of study medication.

Outcome measures

Measure	APD421 5mg n=237 Participants APD421 5mg administered as a single, slow intravenous (IV) push over about two minutes	APD421 10mg n=230 Participants APD421 10mg administered as a single, slow intravenous (IV) push over about two minutes	Placebo n=235 Participants Matching placebo administered as a single, slow, IV push over about two minutes
Number of Participants With Complete Response (Success of Initial PONV Treatment)	80 Participants	96 Participants	67 Participants

SECONDARY outcome

Timeframe: 0-2 hours after administration of study medication

Population: Modified ITT population

Success of initial PONV treatment, where success is defined as no emetic episodes (vomiting or retching) from 30 minutes* to 2 hours after administration of study medication and no administration of anti-emetic rescue medication at any time in the 2-hour period after administration of study medication.

Outcome measures

Measure	APD421 5mg n=237 Participants APD421 5mg administered as a single, slow intravenous (IV) push over about two minutes	APD421 10mg n=230 Participants APD421 10mg administered as a single, slow intravenous (IV) push over about two minutes	Placebo n=235 Participants Matching placebo administered as a single, slow, IV push over about two minutes
Number of Participants With Complete Response 0-2 Hrs	134 Participants	160 Participants	116 Participants

SECONDARY outcome

Timeframe: 0-4 hours after administration of study medication

Population: Modified ITT population

Success of initial PONV treatment, where success is defined as no emetic episodes (vomiting or retching) from 30 minutes* to 4 hours after administration of study medication and no administration of anti-emetic rescue medication at any time in the 4-hour period after administration of study medication.

Outcome measures

Measure	APD421 5mg n=237 Participants APD421 5mg administered as a single, slow intravenous (IV) push over about two minutes	APD421 10mg n=230 Participants APD421 10mg administered as a single, slow intravenous (IV) push over about two minutes	Placebo n=235 Participants Matching placebo administered as a single, slow, IV push over about two minutes
Number of Participants With Complete Response 0-4 Hrs	105 Participants	136 Participants	87 Participants

SECONDARY outcome

Timeframe: 0-6 hours after administration of study medication

Population: Modified ITT population

Success of initial PONV treatment, where success is defined as no emetic episodes (vomiting or retching) from 30 minutes to 6 hours after administration of study medication and no administration of anti-emetic rescue medication at any time in the 6-hour period after administration of study medication.

Outcome measures

Measure	APD421 5mg n=237 Participants APD421 5mg administered as a single, slow intravenous (IV) push over about two minutes	APD421 10mg n=230 Participants APD421 10mg administered as a single, slow intravenous (IV) push over about two minutes	Placebo n=235 Participants Matching placebo administered as a single, slow, IV push over about two minutes
Number of Participants With Complete Response 0-6 Hrs	99 Participants	121 Participants	77 Participants

SECONDARY outcome

Timeframe: 0-24 hours after study drug administration

Population: Modified ITT population

Time to first violation of the criteria for complete response

Outcome measures

Measure	APD421 5mg n=237 Participants APD421 5mg administered as a single, slow intravenous (IV) push over about two minutes	APD421 10mg n=230 Participants APD421 10mg administered as a single, slow intravenous (IV) push over about two minutes	Placebo n=235 Participants Matching placebo administered as a single, slow, IV push over about two minutes
Time to Treatment Failure	188 minutes Interval 43.0 to Treatment failure occurred in less than 75% of patients	443 minutes Interval 70.0 to Treatment failure occurred in less than 75% of patients	120 minutes Interval 35.0 to Treatment failure occurred in less than 75% of patients

SECONDARY outcome

Timeframe: 30 mins to 24 hours after study drug administration

Number of patients experiencing vomiting or retching during the time period from 30 minutes to 24 hours after administration of study medication

Outcome measures

Measure	APD421 5mg n=237 Participants APD421 5mg administered as a single, slow intravenous (IV) push over about two minutes	APD421 10mg n=230 Participants APD421 10mg administered as a single, slow intravenous (IV) push over about two minutes	Placebo n=235 Participants Matching placebo administered as a single, slow, IV push over about two minutes
Number of Patients With Incidence of Emesis	43 Participants	36 Participants	67 Participants

SECONDARY outcome

Timeframe: 0-24 hours after study drug administration

Population: Modified ITT population

Number of patients receiving pre-specified anti-emetic rescue medication at any time in the 24 hours post-treatment period

Outcome measures

Measure	APD421 5mg n=237 Participants APD421 5mg administered as a single, slow intravenous (IV) push over about two minutes	APD421 10mg n=230 Participants APD421 10mg administered as a single, slow intravenous (IV) push over about two minutes	Placebo n=235 Participants Matching placebo administered as a single, slow, IV push over about two minutes
Number of Patients Receiving Rescue Medication	155 Participants	127 Participants	163 Participants

SECONDARY outcome

Timeframe: 30 mins to 24 hours after study drug administration

Population: Modified ITT population

Number of patients with nausea score ≥4 on an 11-point verbal rating scale (0=no nausea, 10=worst possible nausea, therefore higher value is worse outcome) during the time period from 30 minutes to 24 hours after administration of study medication.

Outcome measures

Measure	APD421 5mg n=237 Participants APD421 5mg administered as a single, slow intravenous (IV) push over about two minutes	APD421 10mg n=230 Participants APD421 10mg administered as a single, slow intravenous (IV) push over about two minutes	Placebo n=235 Participants Matching placebo administered as a single, slow, IV push over about two minutes
Number of Patients With an Incidence of Significant Nausea	135 Participants	111 Participants	139 Participants

SECONDARY outcome

Timeframe: 30 mins to 24 hours after drug administration

Population: Modified ITT population

Number of patients with nausea score ≥1 on an 11-point verbal rating scale (0=no nausea, 10=worst possible nausea, therefore higher value is worse outcome) during the time period from 30 minutes to 24 hours after administration of study medication.

Outcome measures

Measure	APD421 5mg n=237 Participants APD421 5mg administered as a single, slow intravenous (IV) push over about two minutes	APD421 10mg n=230 Participants APD421 10mg administered as a single, slow intravenous (IV) push over about two minutes	Placebo n=235 Participants Matching placebo administered as a single, slow, IV push over about two minutes
Number of Patients With an Incidence of Nausea	183 Participants	163 Participants	181 Participants

SECONDARY outcome

Timeframe: 30 mins to 24 hours after study drug administration

Population: Modified ITT population

Highest recorded nausea score on an 11-point verbal rating scale (0=no nausea, 10=worst possible nausea, therefore higher value is worse outcome) during the time period from 30 minutes to 24 hours after administration of study medication.

Outcome measures

Measure	APD421 5mg n=237 Participants APD421 5mg administered as a single, slow intravenous (IV) push over about two minutes	APD421 10mg n=230 Participants APD421 10mg administered as a single, slow intravenous (IV) push over about two minutes	Placebo n=235 Participants Matching placebo administered as a single, slow, IV push over about two minutes
Maximum Severity of Nausea	4.1 Score on a scale Standard Deviation 3.08	3.6 Score on a scale Standard Deviation 3.03	4.2 Score on a scale Standard Deviation 3.04

SECONDARY outcome

Timeframe: 0-180 minutes after study drug administration

Population: Modified ITT population

The evolution score of nausea was calculated as the area under the curve (AUC) of the nausea scores on a scale 0-10 (where 0 is no nausea and 10 is the worst nausea imaginable) obtained at five pre-planned time points: pre-dose (0-min), and 5, 15 and 30 minutes and 2 hours after administration of study medication, as well as any spontaneously reported episodes of nausea during the time period, plotted against time. A higher score represents a worse outcome.

Outcome measures

Measure	APD421 5mg n=237 Participants APD421 5mg administered as a single, slow intravenous (IV) push over about two minutes	APD421 10mg n=230 Participants APD421 10mg administered as a single, slow intravenous (IV) push over about two minutes	Placebo n=235 Participants Matching placebo administered as a single, slow, IV push over about two minutes
Evolution Score of Nausea (0-180 Mins)	6994.7 Score on a scale*min Standard Deviation 5659.6	5637.9 Score on a scale*min Standard Deviation 6046.6	7629.2 Score on a scale*min Standard Deviation 6640.2

Adverse Events

APD421 IV 5mg

Serious events: 6 serious events

Other events: 64 other events

Deaths: 0 deaths

APD421 IV 10mg

Serious events: 3 serious events

Other events: 66 other events

Deaths: 0 deaths

Placebo

Serious events: 5 serious events

Other events: 78 other events

Deaths: 0 deaths

Serious adverse events

Measure	APD421 IV 5mg n=237 participants at risk IV dose of APD421 5mg (IV dose)- was administered to each patient in a double-blind fashion, by slow IV push over about two minutes into a peripheral or central venous cannula.	APD421 IV 10mg n=230 participants at risk IV dose of APD421 10mg (IV dose)- was administered to each patient in a double-blind fashion by slow IV push over about two minutes into a peripheral or central venous cannula.	Placebo n=235 participants at risk IV dose of Placebo (IV dose)- was administered to each patient in a double-blind fashion by slow IV push over about two minutes into a peripheral or central venous cannula.
Injury, poisoning and procedural complications Anastomosis Insufficiency	0.00% 0/237 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours	0.00% 0/230 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours	0.43% 1/235 • Number of events 1 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours
Blood and lymphatic system disorders Leukocytosis	0.00% 0/237 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours	0.00% 0/230 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours	0.43% 1/235 • Number of events 1 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours
Gastrointestinal disorders Non-infectious gastroenteritis	0.00% 0/237 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours	0.00% 0/230 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours	0.43% 1/235 • Number of events 1 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours
Gastrointestinal disorders Unspecified Colitis	0.00% 0/237 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours	0.00% 0/230 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours	0.43% 1/235 • Number of events 1 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours
Gastrointestinal disorders Intra-abdominal Hematoma	0.00% 0/237 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours	0.00% 0/230 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours	0.43% 1/235 • Number of events 1 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours
Gastrointestinal disorders Intractable vomiting	0.00% 0/237 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours	0.00% 0/230 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours	0.43% 1/235 • Number of events 1 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours
Injury, poisoning and procedural complications Post procedural hemorrhage	0.42% 1/237 • Number of events 1 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours	0.00% 0/230 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours	0.00% 0/235 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours
Infections and infestations Abscess Presacral	0.42% 1/237 • Number of events 1 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours	0.00% 0/230 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours	0.00% 0/235 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours
Eye disorders Fatty tissue prolapse at the tempral lobe	0.42% 1/237 • Number of events 1 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours	0.00% 0/230 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours	0.00% 0/235 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours
Nervous system disorders Numbness in the leg	0.42% 1/237 • Number of events 1 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours	0.00% 0/230 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours	0.00% 0/235 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours
Investigations Postoperative rise in creatinine	0.42% 1/237 • Number of events 1 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours	0.00% 0/230 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours	0.00% 0/235 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours
Injury, poisoning and procedural complications Post cholecystectomy bile leak	0.42% 1/237 • Number of events 1 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours	0.00% 0/230 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours	0.00% 0/235 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours
Infections and infestations Urinary tract infection	0.00% 0/237 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours	0.43% 1/230 • Number of events 1 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours	0.00% 0/235 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours
Cardiac disorders Acute Myocardial Infarction	0.00% 0/237 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours	0.43% 1/230 • Number of events 1 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours	0.00% 0/235 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours
Injury, poisoning and procedural complications Postoperative Ileus	0.00% 0/237 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours	0.43% 1/230 • Number of events 1 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours	0.00% 0/235 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours
Gastrointestinal disorders Gastrointestinal bleed	0.00% 0/237 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours	0.43% 1/230 • Number of events 1 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours	0.00% 0/235 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours
Psychiatric disorders Mental status changes	0.00% 0/237 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours	0.43% 1/230 • Number of events 1 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours	0.00% 0/235 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours

Other adverse events

Measure	APD421 IV 5mg n=237 participants at risk IV dose of APD421 5mg (IV dose)- was administered to each patient in a double-blind fashion, by slow IV push over about two minutes into a peripheral or central venous cannula.	APD421 IV 10mg n=230 participants at risk IV dose of APD421 10mg (IV dose)- was administered to each patient in a double-blind fashion by slow IV push over about two minutes into a peripheral or central venous cannula.	Placebo n=235 participants at risk IV dose of Placebo (IV dose)- was administered to each patient in a double-blind fashion by slow IV push over about two minutes into a peripheral or central venous cannula.
Gastrointestinal disorders Nausea	12.7% 30/237 • Number of events 33 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours	11.7% 27/230 • Number of events 28 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours	12.8% 30/235 • Number of events 32 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours
Gastrointestinal disorders Flatulence	5.5% 13/237 • Number of events 13 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours	5.7% 13/230 • Number of events 13 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours	7.7% 18/235 • Number of events 18 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours
Gastrointestinal disorders Constipation	5.5% 13/237 • Number of events 13 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours	4.8% 11/230 • Number of events 11 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours	7.2% 17/235 • Number of events 17 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours
Gastrointestinal disorders Vomiting	4.6% 11/237 • Number of events 14 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours	4.3% 10/230 • Number of events 11 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours	5.5% 13/235 • Number of events 13 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours
Nervous system disorders Headache	4.2% 10/237 • Number of events 10 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours	4.3% 10/230 • Number of events 10 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours	7.2% 17/235 • Number of events 17 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours
General disorders Infusion site pain	3.4% 8/237 • Number of events 8 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours	5.2% 12/230 • Number of events 12 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours	4.3% 10/235 • Number of events 10 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours
General disorders Pruritus	3.0% 7/237 • Number of events 7 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours	4.3% 10/230 • Number of events 10 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours	5.5% 13/235 • Number of events 13 • 7 days Any AE that is serious, occurring during the relevant study period (from study drug administration to 7-day follow-up), irrespective of the treatment received by the subject, must be reported to the Pharmacovigilance provider within 24 hours

Additional Information

Dr Gabriel Fox

Acacia Pharma

Phone: 01223875919764

Email: GabrielFox@acaciapharma.com

Results disclosure agreements

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