Trial Outcomes & Findings for Safety and Efficacy of Intravenous Acetaminophen (IV APAP) in Adult Inpatients (NCT NCT00598559)

NCT ID: NCT00598559

Last Updated: 2016-10-21

Results Overview

Number of subjects who experienced at least one treatment emergent adverse event (TEAE). A TEAE is an adverse event that occurs on or after the first dose of study medication (T0).

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 213 participants
• Primary outcome timeframe: T0 (first dose of IV APAP or randomization to SOC group) to Day 7 - 12 Follow-up
• Results posted on: 2016-10-21

Participant Flow

Open label study conducted in the US from 21 Feb 2008 -12 Aug 2008

Participant milestones

Measure	IV Acetaminophen 1 Gram Every 6 Hours All Subjects Randomized to Receive IV acetaminophen 1 gram administered every 6 hours.	IV Acetaminophen 650 Milligram Every 4 Hours All Subjects Randomized to Receive 650 mg IV acetaminophen administered every 4 hours.	Standard of Care (SOC) All Subjects Randomized to Receive standard of care treatment under the discretion of the Investigator and the medical staff caring for them.
Overall Study STARTED	92	91	30
Overall Study COMPLETED	65	63	27
Overall Study NOT COMPLETED	27	28	3

Reasons for withdrawal

Measure	IV Acetaminophen 1 Gram Every 6 Hours All Subjects Randomized to Receive IV acetaminophen 1 gram administered every 6 hours.	IV Acetaminophen 650 Milligram Every 4 Hours All Subjects Randomized to Receive 650 mg IV acetaminophen administered every 4 hours.	Standard of Care (SOC) All Subjects Randomized to Receive standard of care treatment under the discretion of the Investigator and the medical staff caring for them.
Overall Study Adverse Event	11	7	0
Overall Study Withdrawal by Subject	2	2	0
Overall Study Protocol Non-compliance	1	0	0
Overall Study Early discharge from hospital	9	12	3
Overall Study Subject unable/unwilling to attend visit	4	7	0

Baseline Characteristics

Safety and Efficacy of Intravenous Acetaminophen (IV APAP) in Adult Inpatients

Baseline characteristics by cohort

Measure	IV Acetaminophen 1g q6h n=92 Participants All Subjects Randomized to Receive IV acetaminophen 1g administered every 6 hours.	IV Acetaminophen 650 mg q4h n=91 Participants All Subjects Randomized to Receive 650 mg IV acetaminophen administered every 4 hours.	Standard of Care (SOC) n=30 Participants All Subjects Randomized to Receive standard of care treatment under the discretion of the Investigator and the medical staff caring for them.	Total n=213 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	48 Participants n=5 Participants	54 Participants n=7 Participants	17 Participants n=5 Participants	119 Participants n=4 Participants
Age, Categorical >=65 years	44 Participants n=5 Participants	37 Participants n=7 Participants	13 Participants n=5 Participants	94 Participants n=4 Participants
Sex: Female, Male Female	49 Participants n=5 Participants	44 Participants n=7 Participants	17 Participants n=5 Participants	110 Participants n=4 Participants
Sex: Female, Male Male	43 Participants n=5 Participants	47 Participants n=7 Participants	13 Participants n=5 Participants	103 Participants n=4 Participants

PRIMARY outcome

Timeframe: T0 (first dose of IV APAP or randomization to SOC group) to Day 7 - 12 Follow-up

Population: Safety analyses were conducted using the mITT population, defined as subjects who were randomized to the IV acetaminophen groups and who received at least one dose of IV acetaminophen, and all subjects assigned to the SOC group.

Number of subjects who experienced at least one treatment emergent adverse event (TEAE).

A TEAE is an adverse event that occurs on or after the first dose of study medication (T0).

Outcome measures

Measure	IV Acetaminophen 1 g q6h n=92 Participants mITT Population, IV acetaminophen 1 g administered every 6 hours.	IV Acetaminophen 650 mg q4h n=91 Participants mITT Population, IV acetaminophen 650 mg administered every 4 hours.	Standard of Care (SOC) n=30 Participants mITT Population, Subjects Who Received Standard of Care Treatment.
Number of Subjects Reporting at Least One Treatment-Emergent Adverse Event (TEAE).	77 Participants	86 Participants	26 Participants

PRIMARY outcome

Timeframe: First dose (T0) to within 30 days of the last dose of study medication.

Population: Safety analyses were conducted using the mITT population, defined as subjects who were randomized to the IV acetaminophen groups and who received at least one dose of IV acetaminophen, and all subjects assigned to the SOC group.

Serious TEAE is any untoward medical occurrences at any dose of study medication that:

• results in death
• is life threatening
• requires inpatient hospitalization or causes prolongation of existing hospitalization
• results in persistent or significant disability/incapacity
• is a congenital anomaly/birth defect
• is an important medical event

Outcome measures

Measure	IV Acetaminophen 1 g q6h n=92 Participants mITT Population, IV acetaminophen 1 g administered every 6 hours.	IV Acetaminophen 650 mg q4h n=91 Participants mITT Population, IV acetaminophen 650 mg administered every 4 hours.	Standard of Care (SOC) n=30 Participants mITT Population, Subjects Who Received Standard of Care Treatment.
Subjects Who Experienced at Least One Serious Treatment-Emergent Adverse Event (TEAE)	14 Participants	11 Participants	3 Participants

SECONDARY outcome

Timeframe: End of Day 5 (prior to discharge)

Population: Analyses were conducted using the mITT population, defined as subjects who were randomized to the IV acetaminophen groups and who received at least one dose of IV acetaminophen, and all subjects assigned to the SOC group.

Using a four point categorical scale 0= poor, 1= fair, 2= good, 3= excellent, comparisons of subject's Global Evaluations of the level of satisfaction with side effects related to study treatment at End of Day 5 (prior to discharge)

Outcome measures

Measure	IV Acetaminophen 1 g q6h n=64 Participants mITT Population, IV acetaminophen 1 g administered every 6 hours.	IV Acetaminophen 650 mg q4h n=63 Participants mITT Population, IV acetaminophen 650 mg administered every 4 hours.	Standard of Care (SOC) n=26 Participants mITT Population, Subjects Who Received Standard of Care Treatment.
Subject Global Evaluation of the Level of Satisfaction With Side Effects Related to Study Treatments	2.5 Units on a scale Standard Deviation 0.78	2.5 Units on a scale Standard Deviation 0.67	2.0 Units on a scale Standard Deviation 0.85

SECONDARY outcome

Timeframe: Study period lookback at Day 7

Population: Analyses were conducted using the mITT population, defined as subjects who were randomized to the IV acetaminophen groups and who received at least one dose of IV acetaminophen, and all subjects assigned to the SOC group.

Using a four point categorical scale 0= poor, 1= fair, 2= good, 3= excellent, comparisons of subject's Global Evaluations of the level of satisfaction with study treatments looking back over the entire treatment period was conducted at Day 7.

Outcome measures

Measure	IV Acetaminophen 1 g q6h n=81 Participants mITT Population, IV acetaminophen 1 g administered every 6 hours.	IV Acetaminophen 650 mg q4h n=78 Participants mITT Population, IV acetaminophen 650 mg administered every 4 hours.	Standard of Care (SOC) n=26 Participants mITT Population, Subjects Who Received Standard of Care Treatment.
Subject Global Evaluation of the Level of Satisfaction With Study Treatments Looking Back Over the Entire Treatment Period.	2.4 Units on a scale Standard Deviation 0.75	2.3 Units on a scale Standard Deviation 0.74	2.2 Units on a scale Standard Deviation 0.61

Adverse Events

IV Acetaminophen 1 Gram Every 6 Hours

Serious events: 14 serious events

Other events: 60 other events

Deaths: 0 deaths

IV Acetaminophen 650 Milligram Every 4 Hours

Serious events: 11 serious events

Other events: 68 other events

Deaths: 0 deaths

Standard of Care (SOC)

Serious events: 3 serious events

Other events: 18 other events

Deaths: 0 deaths

Serious adverse events

Measure	IV Acetaminophen 1 Gram Every 6 Hours n=92 participants at risk All Subjects Randomized to Receive IV acetaminophen 1 gram administered every 6 hours.	IV Acetaminophen 650 Milligram Every 4 Hours n=91 participants at risk All Subjects Randomized to Receive 650 mg IV acetaminophen administered every 4 hours.	Standard of Care (SOC) n=30 participants at risk All Subjects Randomized to Receive standard of care treatment under the discretion of the Investigator and the medical staff caring for them.
Infections and infestations Abscess	0.00% 0/92 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	1.1% 1/91 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	0.00% 0/30 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	1.1% 1/92 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	0.00% 0/91 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	0.00% 0/30 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.
Cardiac disorders Cardiac arrest	1.1% 1/92 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	0.00% 0/91 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	0.00% 0/30 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/92 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	0.00% 0/91 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	3.3% 1/30 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.
Gastrointestinal disorders Gastric ulcer haemorrhage	0.00% 0/92 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	1.1% 1/91 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	0.00% 0/30 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.
Injury, poisoning and procedural complications Gastrointestinal anastomotic leak	1.1% 1/92 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	0.00% 0/91 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	0.00% 0/30 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.
Vascular disorders Haematoma	0.00% 0/92 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	1.1% 1/91 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	0.00% 0/30 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.
Investigations Hepatic enzyme increased	0.00% 0/92 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	2.2% 2/91 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	0.00% 0/30 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.
Gastrointestinal disorders Intestinal obstruction	1.1% 1/92 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	0.00% 0/91 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	0.00% 0/30 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.
Psychiatric disorders Mental status changes	1.1% 1/92 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	0.00% 0/91 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	0.00% 0/30 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.
General disorders Multi-organ failure	1.1% 1/92 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	1.1% 1/91 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	0.00% 0/30 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.
Cardiac disorders Myocardial infarction	1.1% 1/92 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	1.1% 1/91 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	0.00% 0/30 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.
Gastrointestinal disorders Oesophageal haemorrhage	1.1% 1/92 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	0.00% 0/91 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	0.00% 0/30 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.
Infections and infestations Pelvic abscess	1.1% 1/92 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	0.00% 0/91 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	0.00% 0/30 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.
Infections and infestations Perirectal abscess	0.00% 0/92 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	1.1% 1/91 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	0.00% 0/30 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.
Gastrointestinal disorders Peritonitis	1.1% 1/92 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	0.00% 0/91 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	0.00% 0/30 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.
Infections and infestations Pneumonia	1.1% 1/92 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	0.00% 0/91 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	0.00% 0/30 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.
Injury, poisoning and procedural complications Post procedural complication	0.00% 0/92 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	1.1% 1/91 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	0.00% 0/30 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.
Injury, poisoning and procedural complications Postoperative ileus	0.00% 0/92 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	1.1% 1/91 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	3.3% 1/30 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.
Infections and infestations Postoperative wound infection	2.2% 2/92 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	2.2% 2/91 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	0.00% 0/30 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.
Reproductive system and breast disorders Prostatic haemorrhage	1.1% 1/92 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	0.00% 0/91 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	0.00% 0/30 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.
Renal and urinary disorders Renal failure acute	1.1% 1/92 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	0.00% 0/91 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	0.00% 0/30 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/92 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	1.1% 1/91 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	0.00% 0/30 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.
Infections and infestations Sepsis	0.00% 0/92 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	0.00% 0/91 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	3.3% 1/30 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.
Infections and infestations Staphylococcal infection	1.1% 1/92 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	0.00% 0/91 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	0.00% 0/30 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.
Investigations Transaminases increased	0.00% 0/92 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	1.1% 1/91 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	0.00% 0/30 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.
Injury, poisoning and procedural complications Wound dehiscience	0.00% 0/92 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	1.1% 1/91 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	0.00% 0/30 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.
Infections and infestations Wound infection	1.1% 1/92 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	0.00% 0/91 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	0.00% 0/30 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.

Other adverse events

Measure	IV Acetaminophen 1 Gram Every 6 Hours n=92 participants at risk All Subjects Randomized to Receive IV acetaminophen 1 gram administered every 6 hours.	IV Acetaminophen 650 Milligram Every 4 Hours n=91 participants at risk All Subjects Randomized to Receive 650 mg IV acetaminophen administered every 4 hours.	Standard of Care (SOC) n=30 participants at risk All Subjects Randomized to Receive standard of care treatment under the discretion of the Investigator and the medical staff caring for them.
Psychiatric disorders Anxiety	4.3% 4/92 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	2.2% 2/91 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	10.0% 3/30 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.
Blood and lymphatic system disorders Anaemia	12.0% 11/92 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	11.0% 10/91 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	20.0% 6/30 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.
Investigations Breath sounds abnormal	7.6% 7/92 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	6.6% 6/91 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	3.3% 1/30 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.
Gastrointestinal disorders Constipation	19.6% 18/92 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	23.1% 21/91 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	16.7% 5/30 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.
Nervous system disorders Headache	7.6% 7/92 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	5.5% 5/91 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	13.3% 4/30 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.
Vascular disorders Hypertension	6.5% 6/92 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	5.5% 5/91 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	0.00% 0/30 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.
Metabolism and nutrition disorders Hypokalaemia	10.9% 10/92 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	4.4% 4/91 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	6.7% 2/30 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.
Vascular disorders Hypotension	7.6% 7/92 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	9.9% 9/91 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	6.7% 2/30 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.
Psychiatric disorders Insomnia	14.1% 13/92 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	18.7% 17/91 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	16.7% 5/30 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.
Gastrointestinal disorders Nausea	25.0% 23/92 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	37.4% 34/91 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	26.7% 8/30 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.
General disorders Oedema peripheral	7.6% 7/92 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	7.7% 7/91 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	6.7% 2/30 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.
Skin and subcutaneous tissue disorders Pruritus	12.0% 11/92 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	14.3% 13/91 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	6.7% 2/30 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.
Gastrointestinal disorders Vomiting	6.5% 6/92 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	11.0% 10/91 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	3.3% 1/30 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.
Blood and lymphatic system disorders Leukocytosis	3.3% 3/92 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	0.00% 0/91 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	6.7% 2/30 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.
Cardiac disorders Tachycardia	5.4% 5/92 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	3.3% 3/91 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	3.3% 1/30 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.
Gastrointestinal disorders Diarrhoea	5.4% 5/92 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	4.4% 4/91 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	3.3% 1/30 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.
General disorders Pyrexia	4.3% 4/92 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	3.3% 3/91 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	6.7% 2/30 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.
Metabolism and nutrition disorders Hyperglycaemia	5.4% 5/92 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	2.2% 2/91 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	0.00% 0/30 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.
Metabolism and nutrition disorders Hypomagnesaemia	5.4% 5/92 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	2.2% 2/91 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	6.7% 2/30 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.
Vascular disorders Phlebitis	0.00% 0/92 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	1.1% 1/91 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.	6.7% 2/30 • AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose The end of the study date was: * IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater. * SOC:12 days from T0 or maximum assessment date, whichever was greater.

Additional Information

Lawrence Hill

Mallinckrodt Pharmaceuticals

Phone: 908-238-6370

Email: lawrence.hill@mallinckrodt.com

Results disclosure agreements

• Principal investigator is a sponsor employee Before any submission is made, Cadence shall be notified of the intention to publish and shall submit the manuscript to Cadence for review and comment.At least 60 days prior to submission for publication, investigator must submit manuscript to sponsor who has 60 days for review and comment. Publication may delayed at Cadence's written request for a period not to exceed 90 days if it contains a disclosure of an invention.
• Publication restrictions are in place

Restriction type: OTHER