Trial Outcomes & Findings for A Controlled Study to Determine the Efficacy and Safety of CL-108 5 mg for Acute Pain and the Prevention of OINV (NCT NCT03657810)

NCT ID: NCT03657810

Last Updated: 2023-03-22

Results Overview

Number and Percentage of participants With opioid-induced nausea and vomiting (OINV) who experienced any Vomiting / use of Anti-Emetic Medication Over 48 Hours

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 349 participants
• Primary outcome timeframe: Up to 48 hours
• Results posted on: 2023-03-22

Participant Flow

This was a Phase 3, double-blind, randomized, placebo- and active-controlled, multiple-dose study conducted at different research centers in the United States

A total of 349 subjects were enrolled into the study, 128 were Screen Failed and 221 were Randomized, 209 were Completed the study and 12 subjects were discontinued.

Participant milestones

Measure	CL-108 Hydrocodone 5 mg/acetaminophen (APAP) 325 mg/promethazine 12.5 mg (CL-108 5 mg) bi-layered tablet CL-108 5 mg: hydrocodone 5 mg/APAP 325 mg/promethazine 12.5 mg	Norco hydrocodone 5 mg/APAP 325 mg Norco: hydrocodone 5 mg/APAP 325 mg	Placebo Placebo 0 mg matching CL-108 Placebo: Placebo matching CL-108
Overall Study STARTED	87	90	44
Overall Study COMPLETED	82	86	41
Overall Study NOT COMPLETED	5	4	3

Reasons for withdrawal

Measure	CL-108 Hydrocodone 5 mg/acetaminophen (APAP) 325 mg/promethazine 12.5 mg (CL-108 5 mg) bi-layered tablet CL-108 5 mg: hydrocodone 5 mg/APAP 325 mg/promethazine 12.5 mg	Norco hydrocodone 5 mg/APAP 325 mg Norco: hydrocodone 5 mg/APAP 325 mg	Placebo Placebo 0 mg matching CL-108 Placebo: Placebo matching CL-108
Overall Study Adverse Event	0	1	0
Overall Study Lack of Efficacy	4	1	3
Overall Study Protocol Violation	1	0	0
Overall Study Lost to Follow-up	0	1	0
Overall Study Not provided	0	1	0

Baseline Characteristics

A Controlled Study to Determine the Efficacy and Safety of CL-108 5 mg for Acute Pain and the Prevention of OINV

Baseline characteristics by cohort

Measure	CL-108 n=87 Participants Hydrocodone 5 mg/APAP 325 mg/promethazine 12.5 mg (CL-108 5 mg) bi-layered tablet CL-108 5 mg: hydrocodone 5 mg/APAP 325 mg/promethazine 12.5 mg	Norco n=90 Participants hydrocodone 5 mg/APAP 325 mg Norco: hydrocodone 5 mg/APAP 325 mg	Placebo n=44 Participants Placebo 0 mg matching CL-108 Placebo: Placebo matching CL-108	Total n=221 Participants Total of all reporting groups
Age, Continuous	43.3 years STANDARD_DEVIATION 12.97 • n=5 Participants	43.5 years STANDARD_DEVIATION 14.74 • n=7 Participants	47.2 years STANDARD_DEVIATION 13.40 • n=5 Participants	44.2 years STANDARD_DEVIATION 13.82 • n=4 Participants
Sex: Female, Male Female	75 Participants n=5 Participants	77 Participants n=7 Participants	40 Participants n=5 Participants	192 Participants n=4 Participants
Sex: Female, Male Male	12 Participants n=5 Participants	13 Participants n=7 Participants	4 Participants n=5 Participants	29 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	27 Participants n=5 Participants	22 Participants n=7 Participants	9 Participants n=5 Participants	58 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	60 Participants n=5 Participants	68 Participants n=7 Participants	35 Participants n=5 Participants	163 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	4 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	12 Participants n=5 Participants	12 Participants n=7 Participants	8 Participants n=5 Participants	32 Participants n=4 Participants
Race (NIH/OMB) White	69 Participants n=5 Participants	73 Participants n=7 Participants	33 Participants n=5 Participants	175 Participants n=4 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	4 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants
Region of Enrollment United States	87 participants n=5 Participants	90 participants n=7 Participants	44 participants n=5 Participants	221 participants n=4 Participants
Weight	79.19 kg STANDARD_DEVIATION 23.427 • n=5 Participants	74.56 kg STANDARD_DEVIATION 18.054 • n=7 Participants	81.86 kg STANDARD_DEVIATION 18.827 • n=5 Participants	77.83 kg STANDARD_DEVIATION 20.592 • n=4 Participants
Height	164.94 cm STANDARD_DEVIATION 9.457 • n=5 Participants	165.09 cm STANDARD_DEVIATION 9.133 • n=7 Participants	164.45 cm STANDARD_DEVIATION 8.256 • n=5 Participants	164.90 cm STANDARD_DEVIATION 9.060 • n=4 Participants
BMI	28.88 kg/m^2 STANDARD_DEVIATION 6.876 • n=5 Participants	27.29 kg/m^2 STANDARD_DEVIATION 5.549 • n=7 Participants	30.26 kg/m^2 STANDARD_DEVIATION 6.358 • n=5 Participants	28.51 kg/m^2 STANDARD_DEVIATION 6.333 • n=4 Participants

PRIMARY outcome

Timeframe: Up to 48 hours

Population: Intent-to-Treat (ITT) Population: The ITT Population comprised all patients who were randomized and who received at least 1 dose of study medication.

Number and Percentage of participants With opioid-induced nausea and vomiting (OINV) who experienced any Vomiting / use of Anti-Emetic Medication Over 48 Hours

Outcome measures

Measure	CL-108 n=87 Participants Hydrocodone 5 mg/APAP 325 mg/promethazine 12.5 mg (CL-108 5 mg) bi-layered tablet CL-108 5 mg: hydrocodone 5 mg/APAP 325 mg/promethazine 12.5 mg	Norco n=90 Participants hydrocodone 5 mg/APAP 325 mg Norco: hydrocodone 5 mg/APAP 325 mg	Placebo n=44 Participants Placebo 0 mg matching CL-108 Placebo: Placebo matching CL-108
Percentage of Participants With OINV Over 48 Hours	8 Participants	31 Participants	4 Participants

PRIMARY outcome

Timeframe: Up to 48 hours

Population: Intent-to-Treat (ITT) Population: The ITT Population comprised all patients who were randomized and who received at least 1 dose of study medication.

The SPID48 endpoint is calculated from the PI-NRS values at baseline, every 30 minutes until hour 12, then every hour (when awake) until hour 48 as follows:

• Each subsequent PI-NRS value is subtracted from the baseline PI-NRS value.
• Each difference is weighted by the elapsed time from the previous PI-NRS value to the current one.
• The weighed differences are summed to yield the SPID48.

Summed pain intensity differences over 48 hours (SPID48) will be compared for patients treated with CL-108 5 mg and those treated with placebo. Pain intensity will be measured on a 0-10 Pain Intensity Numerical Rating Scale (PI-NRS), where 0 is "no pain" and 10 is "severe pain".

Outcome measures

Measure	CL-108 n=87 Participants Hydrocodone 5 mg/APAP 325 mg/promethazine 12.5 mg (CL-108 5 mg) bi-layered tablet CL-108 5 mg: hydrocodone 5 mg/APAP 325 mg/promethazine 12.5 mg	Norco n=90 Participants hydrocodone 5 mg/APAP 325 mg Norco: hydrocodone 5 mg/APAP 325 mg	Placebo n=44 Participants Placebo 0 mg matching CL-108 Placebo: Placebo matching CL-108
The Sum of Pain Intensity Differences (on PI-NRS) Over 48 Hours (SPID48)	108.5 score on a scale Standard Deviation 80.66	94.8 score on a scale Standard Deviation 69.53	78.7 score on a scale Standard Deviation 62.66

SECONDARY outcome

Timeframe: Up to 48 hours

Population: Intent-to-Treat (ITT) Population: The ITT Population comprised all patients who were randomized and who received at least 1 dose of study medication.

Percentage of patients with complete absence of OINV (no nausea, no vomiting, and no use of anti-emetic medication) over 48 hours comparing CL-108 5 mg to hydrocodone 5 mg/APAP 325 mg)

Outcome measures

Measure	CL-108 n=87 Participants Hydrocodone 5 mg/APAP 325 mg/promethazine 12.5 mg (CL-108 5 mg) bi-layered tablet CL-108 5 mg: hydrocodone 5 mg/APAP 325 mg/promethazine 12.5 mg	Norco n=90 Participants hydrocodone 5 mg/APAP 325 mg Norco: hydrocodone 5 mg/APAP 325 mg	Placebo n=44 Participants Placebo 0 mg matching CL-108 Placebo: Placebo matching CL-108
Percentage of Patients With Complete Absence of OINV (no Nausea, no Vomiting, and no Use of Anti-emetic Medication) Over 48 Hours	50 Participants	34 Participants	27 Participants

SECONDARY outcome

Timeframe: Up to 48 hours

Population: Intent-to-Treat (ITT) Population: The ITT Population comprised all patients who were randomized and who received at least 1 dose of study medication.

Percentage of patients with any vomiting over 48 hours, comparing CL-108 5 mg to hydrocodone 5 mg/APAP 325 mg

Outcome measures

Measure	CL-108 n=87 Participants Hydrocodone 5 mg/APAP 325 mg/promethazine 12.5 mg (CL-108 5 mg) bi-layered tablet CL-108 5 mg: hydrocodone 5 mg/APAP 325 mg/promethazine 12.5 mg	Norco n=90 Participants hydrocodone 5 mg/APAP 325 mg Norco: hydrocodone 5 mg/APAP 325 mg	Placebo n=44 Participants Placebo 0 mg matching CL-108 Placebo: Placebo matching CL-108
Percentage of Patients With Any Vomiting Over 48 Hours	3 Participants	19 Participants	2 Participants

SECONDARY outcome

Timeframe: Up to 48 hours

Population: Intent-to-Treat (ITT) Population: The ITT Population comprised all patients who were randomized and who received at least 1 dose of study medication.

Percentage of patients with any nausea over 48 hours, comparing CL-108 5 mg to hydrocodone 5 mg/APAP 325 mg

Outcome measures

Measure	CL-108 n=87 Participants Hydrocodone 5 mg/APAP 325 mg/promethazine 12.5 mg (CL-108 5 mg) bi-layered tablet CL-108 5 mg: hydrocodone 5 mg/APAP 325 mg/promethazine 12.5 mg	Norco n=90 Participants hydrocodone 5 mg/APAP 325 mg Norco: hydrocodone 5 mg/APAP 325 mg	Placebo n=44 Participants Placebo 0 mg matching CL-108 Placebo: Placebo matching CL-108
Percentage of Patients With Any Nausea Over 48 Hours	36 Participants	55 Participants	15 Participants

SECONDARY outcome

Timeframe: Up to 48 hours

Population: Intent-to-Treat (ITT) Population: The ITT Population comprised all patients who were randomized and who received at least 1 dose of study medication.

Percentage of patients with any nausea or vomiting over 48 hours, comparing CL-108 5 mg to hydrocodone 5 mg/APAP 325 mg

Outcome measures

Measure	CL-108 n=87 Participants Hydrocodone 5 mg/APAP 325 mg/promethazine 12.5 mg (CL-108 5 mg) bi-layered tablet CL-108 5 mg: hydrocodone 5 mg/APAP 325 mg/promethazine 12.5 mg	Norco n=90 Participants hydrocodone 5 mg/APAP 325 mg Norco: hydrocodone 5 mg/APAP 325 mg	Placebo n=44 Participants Placebo 0 mg matching CL-108 Placebo: Placebo matching CL-108
Percentage of Patients With Any Nausea or Vomiting Over 48 Hours	37 Participants	55 Participants	16 Participants

SECONDARY outcome

Timeframe: Day 3 to 7

Population: Intent-to-Treat (ITT) Population: The ITT Population comprised all patients who were randomized and who received at least 1 dose of study medication.

Percentage of patients with any Post-discharge Nausea and Vomiting (PDNV) over Days 3 to 7

Outcome measures

Measure	CL-108 n=87 Participants Hydrocodone 5 mg/APAP 325 mg/promethazine 12.5 mg (CL-108 5 mg) bi-layered tablet CL-108 5 mg: hydrocodone 5 mg/APAP 325 mg/promethazine 12.5 mg	Norco n=90 Participants hydrocodone 5 mg/APAP 325 mg Norco: hydrocodone 5 mg/APAP 325 mg	Placebo n=44 Participants Placebo 0 mg matching CL-108 Placebo: Placebo matching CL-108
Percentage of Patients With Any Post-discharge Nausea and Vomiting (PDNV)	9 Participants	12 Participants	6 Participants

SECONDARY outcome

Timeframe: Day3 to Day7

Population: Intent-to-Treat (ITT) Population: The ITT Population comprised all patients who were randomized and who received at least 1 dose of study medication.

Number of doses of study medication taken over Days 3 to 7

Outcome measures

Measure	CL-108 n=87 Participants Hydrocodone 5 mg/APAP 325 mg/promethazine 12.5 mg (CL-108 5 mg) bi-layered tablet CL-108 5 mg: hydrocodone 5 mg/APAP 325 mg/promethazine 12.5 mg	Norco n=90 Participants hydrocodone 5 mg/APAP 325 mg Norco: hydrocodone 5 mg/APAP 325 mg	Placebo n=44 Participants Placebo 0 mg matching CL-108 Placebo: Placebo matching CL-108
Number of Doses of Study Medication Taken Over Days 3to7	10.0 doses Standard Deviation 7.05	8.4 doses Standard Deviation 7.30	6.2 doses Standard Deviation 5.70

SECONDARY outcome

Timeframe: Day3 to Day7

Population: Intent-to-Treat (ITT) Population: The ITT Population comprised all patients who were randomized and who received at least 1 dose of study medication.

Number of doses of study medication taken per day over Days 3 to 7

Outcome measures

Measure	CL-108 n=87 Participants Hydrocodone 5 mg/APAP 325 mg/promethazine 12.5 mg (CL-108 5 mg) bi-layered tablet CL-108 5 mg: hydrocodone 5 mg/APAP 325 mg/promethazine 12.5 mg	Norco n=90 Participants hydrocodone 5 mg/APAP 325 mg Norco: hydrocodone 5 mg/APAP 325 mg	Placebo n=44 Participants Placebo 0 mg matching CL-108 Placebo: Placebo matching CL-108
Number of Doses of Study Medication Taken Per Day Over Days 3to7 Number of Doses of Study Medication Taken over Day 3	3.0 doses per day Standard Deviation 1.60	2.4 doses per day Standard Deviation 1.83	2.1 doses per day Standard Deviation 1.59
Number of Doses of Study Medication Taken Per Day Over Days 3to7 Number of Doses of Study Medication Taken over Day 4	2.1 doses per day Standard Deviation 1.65	1.9 doses per day Standard Deviation 1.70	1.4 doses per day Standard Deviation 1.45
Number of Doses of Study Medication Taken Per Day Over Days 3to7 Number of Doses of Study Medication Taken over Day 5	1.9 doses per day Standard Deviation 1.81	1.7 doses per day Standard Deviation 1.73	1.1 doses per day Standard Deviation 1.40
Number of Doses of Study Medication Taken Per Day Over Days 3to7 Number of Doses of Study Medication Taken over Day 6	1.8 doses per day Standard Deviation 1.77	1.5 doses per day Standard Deviation 1.72	1.0 doses per day Standard Deviation 1.16
Number of Doses of Study Medication Taken Per Day Over Days 3to7 Number of Doses of Study Medication Taken over Day 7	1.1 doses per day Standard Deviation 1.46	0.9 doses per day Standard Deviation 1.29	0.6 doses per day Standard Deviation 1.06

Adverse Events

CL-108

Serious events: 1 serious events

Other events: 80 other events

Deaths: 0 deaths

Norco

Serious events: 0 serious events

Other events: 79 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 37 other events

Deaths: 0 deaths

Serious adverse events

Measure	CL-108 n=87 participants at risk Hydrocodone 5 mg/APAP 325 mg/promethazine 12.5 mg (CL-108 5 mg) bi-layered tablet CL-108 5 mg: hydrocodone 5 mg/APAP 325 mg/promethazine 12.5 mg	Norco n=90 participants at risk hydrocodone 5 mg/APAP 325 mg Norco: hydrocodone 5 mg/APAP 325 mg	Placebo n=44 participants at risk Placebo 0 mg matching CL-108 Placebo: Placebo matching CL-108
Vascular disorders DEEP VEIN THROMBOSIS RIGHT CALF	1.1% 1/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.

Other adverse events

Measure	CL-108 n=87 participants at risk Hydrocodone 5 mg/APAP 325 mg/promethazine 12.5 mg (CL-108 5 mg) bi-layered tablet CL-108 5 mg: hydrocodone 5 mg/APAP 325 mg/promethazine 12.5 mg	Norco n=90 participants at risk hydrocodone 5 mg/APAP 325 mg Norco: hydrocodone 5 mg/APAP 325 mg	Placebo n=44 participants at risk Placebo 0 mg matching CL-108 Placebo: Placebo matching CL-108
Infections and infestations Postoperative wound infection	0.00% 0/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	2.3% 1/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
Injury, poisoning and procedural complications Contusion	2.3% 2/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	1.1% 1/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
Infections and infestations Localised infection	0.00% 0/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	2.3% 1/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
Infections and infestations Post procedural infection	1.1% 1/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
General disorders Fatigue	1.1% 1/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
General disorders Feeling hot	1.1% 1/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
General disorders Inflammation	0.00% 0/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	1.1% 1/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
General disorders Malaise	1.1% 1/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
Infections and infestations Cellulitis	0.00% 0/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	2.3% 1/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
Ear and labyrinth disorders Motion sickness	0.00% 0/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	1.1% 1/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
Eye disorders Vision blurred	0.00% 0/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	1.1% 1/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	2.3% 1/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
Gastrointestinal disorders Nausea	43.7% 38/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	60.0% 54/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	38.6% 17/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
Gastrointestinal disorders Dry mouth	35.6% 31/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	17.8% 16/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	18.2% 8/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
Gastrointestinal disorders Constipation	26.4% 23/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	26.7% 24/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	9.1% 4/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
Gastrointestinal disorders Vomiting	3.4% 3/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	22.2% 20/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	6.8% 3/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
Gastrointestinal disorders Diarrhoea	2.3% 2/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	1.1% 1/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	11.4% 5/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
Gastrointestinal disorders Dyspepsia	1.1% 1/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	1.1% 1/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	2.3% 1/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
Gastrointestinal disorders Flatulence	1.1% 1/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	1.1% 1/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	2.3% 1/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
Gastrointestinal disorders Abdominal pain upper	1.1% 1/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	2.3% 1/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
Gastrointestinal disorders Abdominal mass	0.00% 0/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	1.1% 1/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
Gastrointestinal disorders Abdominal pain lower	1.1% 1/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
General disorders Pyrexia	2.3% 2/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	2.2% 2/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	6.8% 3/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
General disorders Asthenia	0.00% 0/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	4.5% 2/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
General disorders Chest discomfort	0.00% 0/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	4.5% 2/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
General disorders Infusion site extravasation	0.00% 0/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	2.2% 2/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
General disorders Administration site nodule	0.00% 0/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	1.1% 1/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
General disorders Chills	1.1% 1/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
Injury, poisoning and procedural complications Incision site pain	0.00% 0/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	1.1% 1/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
Metabolism and nutrition disorders Decreased appetite	2.3% 2/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	2.3% 1/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
Metabolism and nutrition disorders Dehydration	0.00% 0/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	1.1% 1/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
Musculoskeletal and connective tissue disorders Muscle spasms	1.1% 1/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	1.1% 1/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	4.5% 2/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
Musculoskeletal and connective tissue disorders Pain in extremity	1.1% 1/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	1.1% 1/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
Musculoskeletal and connective tissue disorders Arthralgia	1.1% 1/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	1.1% 1/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
Musculoskeletal and connective tissue disorders Neck pain	1.1% 1/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
Nervous system disorders Somnolence	52.9% 46/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	44.4% 40/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	20.5% 9/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
Nervous system disorders Headache	25.3% 22/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	28.9% 26/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	27.3% 12/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
Nervous system disorders Dizziness	25.3% 22/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	25.6% 23/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	13.6% 6/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
Nervous system disorders Disturbance in attention	11.5% 10/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	7.8% 7/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	6.8% 3/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
Nervous system disorders Syncope	2.3% 2/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
Nervous system disorders Tremor	1.1% 1/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	2.3% 1/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
Nervous system disorders Burning sensation	1.1% 1/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
Nervous system disorders Dizziness postural	1.1% 1/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
Nervous system disorders Dysgeusia	0.00% 0/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	2.3% 1/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
Nervous system disorders Paraesthesia	0.00% 0/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	1.1% 1/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
Nervous system disorders Sciatica	0.00% 0/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	1.1% 1/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
Psychiatric disorders Confusional state	8.0% 7/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	1.1% 1/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	4.5% 2/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
Psychiatric disorders Anxiety	1.1% 1/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
Psychiatric disorders Insomnia	1.1% 1/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
Psychiatric disorders Nervousness	1.1% 1/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
Renal and urinary disorders Dysuria	2.3% 2/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	1.1% 1/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	2.3% 1/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
Renal and urinary disorders Polyuria	1.1% 1/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	2.2% 2/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	2.3% 2/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	2.3% 1/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	2.3% 1/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
Respiratory, thoracic and mediastinal disorders Dry throat	1.1% 1/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	1.1% 1/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	1.1% 1/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
Skin and subcutaneous tissue disorders Pruritus	26.4% 23/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	23.3% 21/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	18.2% 8/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
Skin and subcutaneous tissue disorders Hyperhidrosis	1.1% 1/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	3.3% 3/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
Skin and subcutaneous tissue disorders Rash	2.3% 2/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	2.2% 2/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
Skin and subcutaneous tissue disorders Erythema	1.1% 1/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	1.1% 1/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	2.3% 1/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
Skin and subcutaneous tissue disorders Cold sweat	0.00% 0/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	2.2% 2/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
Skin and subcutaneous tissue disorders Dermatitis contact	2.3% 2/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
Skin and subcutaneous tissue disorders Urticaria	1.1% 1/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	1.1% 1/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	2.3% 1/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
Skin and subcutaneous tissue disorders Decubitus ulcer	0.00% 0/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	2.3% 1/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
Skin and subcutaneous tissue disorders Pruritus generalised	0.00% 0/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	1.1% 1/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
Skin and subcutaneous tissue disorders Rash papular	1.1% 1/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
Vascular disorders Deep vein thrombosis	1.1% 1/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
Vascular disorders Flushing	1.1% 1/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
Vascular disorders Hypertension	1.1% 1/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.
Vascular disorders Hypotension	0.00% 0/87 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	1.1% 1/90 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.	0.00% 0/44 • Up to Visit 3 (Approximately 8 days after surgery) A drug-related (TEAE) Treatment-emergent adverse event is defined as a TEAE with a relatedness of Possible or Probable. A subject is counted once in the most severe category if the subject reported one or more events, but different severity.

Additional Information

Bernard P. Schachtel, MD, Chief Scientific Officer

Charleston Laboratories, Inc.

Phone: 561.379.8726

Email: bschachtel@charlestonlabs.com

Results disclosure agreements

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