Trial Outcomes & Findings for Study to Evaluate Analgesic Effect of IV Administration of Kappa Agonist CR845 For Hysterectomy Surgery (NCT NCT01361568)

NCT ID: NCT01361568

Last Updated: 2014-05-29

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 203 participants
• Primary outcome timeframe: 24 hours
• Results posted on: 2014-05-29

Participant Flow

Participant milestones

Measure	Placebo-Placebo Placebo administered both preoperatively and postoperatively	Placebo-CR845 Placebo administered preoperatively and CR845 administered postoperatively	CR845-CR845 CR845 administered both preoperatively and postoperatively	CR845-Placebo CR845 administered preoperatively and placebo administered postoperatively	CR845-No Postoperative Treatment CR845 administered preoperatively and no study drug administered postoperatively	Placebo-No Postoperative Treatment Placebo administered preoperatively and no study drug administered postoperatively
Overall Study STARTED	71	71	20	21	7	13
Overall Study COMPLETED	69	70	20	21	6	11
Overall Study NOT COMPLETED	2	1	0	0	1	2

Reasons for withdrawal

Measure	Placebo-Placebo Placebo administered both preoperatively and postoperatively	Placebo-CR845 Placebo administered preoperatively and CR845 administered postoperatively	CR845-CR845 CR845 administered both preoperatively and postoperatively	CR845-Placebo CR845 administered preoperatively and placebo administered postoperatively	CR845-No Postoperative Treatment CR845 administered preoperatively and no study drug administered postoperatively	Placebo-No Postoperative Treatment Placebo administered preoperatively and no study drug administered postoperatively
Overall Study Adverse Event	0	0	0	0	1	0
Overall Study Physician Decision	0	0	0	0	0	1
Overall Study Withdrawal by Subject	2	1	0	0	0	1

Baseline Characteristics

Study to Evaluate Analgesic Effect of IV Administration of Kappa Agonist CR845 For Hysterectomy Surgery

Baseline characteristics by cohort

Measure	Placebo-Placebo n=71 Participants Placebo administered both preoperatively and postoperatively	Placebo-CR845 n=71 Participants Placebo administered preoperatively and CR845 administered postoperatively	CR845-CR845 n=20 Participants CR845 administered both preoperatively and postoperatively	CR845-Placebo n=21 Participants CR845 administered preoperatively and placebo administered postoperatively	CR845-No Postoperative Treatment n=7 Participants CR845 administered preoperatively and no study drug administered postoperatively	Placebo-No Postoperative Treatment n=13 Participants Placebo administered preoperatively and no study drug administered postoperatively	Total n=203 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	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants
Age, Categorical Between 18 and 65 years	71 Participants n=5 Participants	70 Participants n=7 Participants	20 Participants n=5 Participants	21 Participants n=4 Participants	7 Participants n=21 Participants	13 Participants n=8 Participants	202 Participants n=8 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	1 Participants n=8 Participants
Age, Continuous	42.7 years STANDARD_DEVIATION 8.60 • n=5 Participants	44.3 years STANDARD_DEVIATION 9.69 • n=7 Participants	43.8 years STANDARD_DEVIATION 7.14 • n=5 Participants	40.0 years STANDARD_DEVIATION 6.88 • n=4 Participants	55.9 years STANDARD_DEVIATION 7.84 • n=21 Participants	45.3 years STANDARD_DEVIATION 7.93 • n=8 Participants	43.7 years STANDARD_DEVIATION 8.97 • n=8 Participants
Sex: Female, Male Female	71 Participants n=5 Participants	71 Participants n=7 Participants	20 Participants n=5 Participants	21 Participants n=4 Participants	7 Participants n=21 Participants	13 Participants n=8 Participants	203 Participants n=8 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants
Region of Enrollment United States	71 participants n=5 Participants	71 participants n=7 Participants	20 participants n=5 Participants	21 participants n=4 Participants	7 participants n=21 Participants	13 participants n=8 Participants	203 participants n=8 Participants

PRIMARY outcome

Timeframe: 24 hours

Population: The primary analysis included all patients in the modified Intent-to-Treat (mITT) population who re-randomized in the postoperative period, where time 0 was the start time of the postoperative study drug infusion.

Outcome measures

Measure	Placebo-Placebo n=71 Participants Placebo administered both preoperatively and postoperatively	Placebo-CR845 n=71 Participants Placebo administered preoperatively and CR845 administered postoperatively	CR845-CR845 n=20 Participants CR845 administered both preoperatively and postoperatively	CR845-Placebo n=21 Participants CR845 administered preoperatively and placebo administered postoperatively
Total Morphine Consumption in the First 24 Hours Following Postoperative Study Drug Treatment	21.9 mg Standard Error 1.89	17.6 mg Standard Error 1.65	13.9 mg Standard Error 2.20	19.8 mg Standard Error 3.03

SECONDARY outcome

Timeframe: 0 to 24 hours

Population: The analysis included all patients in the modified Intent-to-Treat (mITT) population who re-randomized in the postoperative period, where time 0 was the start time of the postoperative study drug infusion, and did not have a missing baseline pain intensity score.

Patients reported their pain intensity using a visual analogue scale (VAS) from 0 to 100 mm, where 0 mm represented "No Pain" and 100 mm represented the "Worst Pain You Can Imagine". SPID 0-24 represents the cumulative time-weighted sum of the pain intensity difference (PID) scores between each assessment timepoint following the postoperative administration of study drug (i.e. 0 to 15 min, 15 to 30 min, etc.) over 24 hours. Pain intensity assessments were measured at baseline (entry pain score), then at 15, 30, 45, 60, 90, 120, 150, 180, 240, 360, 480, 720, 960, and 1440 minutes after the start of the infusion of study drug following surgery.

Negative SPID values represent a decrease in pain intensity (i.e. lower values indicate a greater reduction in pain).

Outcome measures

Measure	Placebo-Placebo n=71 Participants Placebo administered both preoperatively and postoperatively	Placebo-CR845 n=71 Participants Placebo administered preoperatively and CR845 administered postoperatively	CR845-CR845 n=20 Participants CR845 administered both preoperatively and postoperatively	CR845-Placebo n=19 Participants CR845 administered preoperatively and placebo administered postoperatively
Summed Pain Intensity Difference From 0-24 Hours (SPID 0-24) Following Postoperative Study Drug Treatment Using Last Observation Carried Forward (LOCF)	-413.1 units on a scale * hours Standard Error 67.8	-643.2 units on a scale * hours Standard Error 58.11	-833.1 units on a scale * hours Standard Error 124.8	-673.5 units on a scale * hours Standard Error 152.36

SECONDARY outcome

Timeframe: 2 to 24 hours (post-PACU)

Population: The analysis included all patients in the modified Intent-to-Treat (mITT) population who re-randomized in the postoperative period, where time 0 was the start time of the postoperative study drug infusion. Morphine consumption was calculated for the 2-24 hour period, after patients were transferred out of the PACU.

Outcome measures

Measure	Placebo-Placebo n=71 Participants Placebo administered both preoperatively and postoperatively	Placebo-CR845 n=71 Participants Placebo administered preoperatively and CR845 administered postoperatively	CR845-CR845 n=20 Participants CR845 administered both preoperatively and postoperatively	CR845-Placebo n=21 Participants CR845 administered preoperatively and placebo administered postoperatively
Morphine Consumption Following Postoperative Study Drug Treatment in the 2-24 Hour Period After Recovery in the Post-Anesthesia Care Unit (Post-PACU)	14.38 mg Standard Error 1.35	11.07 mg Standard Error 1.17	7.99 mg Standard Error 2.03	11.33 mg Standard Error 2.11

SECONDARY outcome

Timeframe: 0 to 2 hours

Population: The analysis included all patients in the modified Intent-to-Treat (mITT) population who re-randomized in the postoperative period, where time 0 was the start time of the postoperative study drug infusion, and did not have a missing baseline pain intensity score.

Patients reported their pain relief using a 5-point categorical scale of 0 to 4 (0 = No Relief, 1 = A Little Relief, 2 = Some Relief, 3 = A Lot of Relief and 4 = Complete Relief). TOTPAR 0-2 was represents the cumulative time-weighted sum of the pain relief (PR) scores between each assessment timepoint following the postoperative administration of study drug (i.e. 15 to 30 min, 30 to 45 min, etc.) over the first 2 hours. Pain relief assessments were measured at 15, 30, 45, 60, 90, 120 minutes after the start of the infusion of study drug following surgery.

Positive TOTPAR values represent an increase in pain relief.

Outcome measures

Measure	Placebo-Placebo n=71 Participants Placebo administered both preoperatively and postoperatively	Placebo-CR845 n=71 Participants Placebo administered preoperatively and CR845 administered postoperatively	CR845-CR845 n=20 Participants CR845 administered both preoperatively and postoperatively	CR845-Placebo n=19 Participants CR845 administered preoperatively and placebo administered postoperatively
Total Pain Relief Within the First 2 Hours (TOTPAR 0-2) Following Postoperative Study Drug Treatment Using LOCF	1.4 units on a scale * hours Standard Error 0.16	2.1 units on a scale * hours Standard Error 0.19	2.4 units on a scale * hours Standard Error 0.48	1.5 units on a scale * hours Standard Error 0.40

SECONDARY outcome

Timeframe: At 24 hours

Population: The responder analysis included all patients in the modified Intent-to-Treat (mITT) population and compared patients that received any dose of CR845 (preoperatively and/or postoperatively) to patients that only received placebo.

Responders = Excellent or Very Good; Non-Responders = Fair or Poor. Patient who reported a score of "Good" were not included in the analysis as the midpoint cannot be unambiguously assigned for a binary outcome measurement.

Outcome measures

Measure	Placebo-Placebo n=55 Participants Placebo administered both preoperatively and postoperatively	Placebo-CR845 n=90 Participants Placebo administered preoperatively and CR845 administered postoperatively	CR845-CR845 CR845 administered both preoperatively and postoperatively	CR845-Placebo CR845 administered preoperatively and placebo administered postoperatively
Global Evaluation Responder Analysis	27 Responder Count	68 Responder Count	—	—

SECONDARY outcome

Timeframe: Up to 24 hours

Population: All patients in the modified Intent-to-Treat (mITT) population and compared patients that received any dose of CR845 (preoperatively and/or postoperatively) to patients that only received placebo.

Outcome measures

Measure	Placebo-Placebo n=84 Participants Placebo administered both preoperatively and postoperatively	Placebo-CR845 n=119 Participants Placebo administered preoperatively and CR845 administered postoperatively	CR845-CR845 CR845 administered both preoperatively and postoperatively	CR845-Placebo CR845 administered preoperatively and placebo administered postoperatively
Total Number of Patients Reporting At Least One Episode of Nausea	51.2 percentage of patients	26.1 percentage of patients	—	—

SECONDARY outcome

Timeframe: Up to 24 hours

Population: All patients in the modified Intent-to-Treat (mITT) population and compared patients that received any dose of CR845 (preoperatively and/or postoperatively) to patients that only received placebo.

Outcome measures

Measure	Placebo-Placebo n=84 Participants Placebo administered both preoperatively and postoperatively	Placebo-CR845 n=119 Participants Placebo administered preoperatively and CR845 administered postoperatively	CR845-CR845 CR845 administered both preoperatively and postoperatively	CR845-Placebo CR845 administered preoperatively and placebo administered postoperatively
Total Number of Patients Reporting At Least One Episode of Vomiting	8.3 percentage of patients	1.7 percentage of patients	—	—

Adverse Events

Placebo-Placebo

Serious events: 0 serious events

Other events: 59 other events

Deaths: 0 deaths

Placebo-CR845

Serious events: 6 serious events

Other events: 62 other events

Deaths: 0 deaths

CR845-CR845

Serious events: 3 serious events

Other events: 19 other events

Deaths: 0 deaths

CR845-Placebo

Serious events: 0 serious events

Other events: 15 other events

Deaths: 0 deaths

CR845-No Postoperative Treatment

Serious events: 3 serious events

Other events: 7 other events

Deaths: 0 deaths

Placebo-No Postoperative Treatment

Serious events: 1 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo-Placebo n=71 participants at risk Placebo administered both preoperatively and postoperatively	Placebo-CR845 n=71 participants at risk Placebo administered preoperatively and CR845 administered postoperatively	CR845-CR845 n=20 participants at risk CR845 administered both preoperatively and postoperatively	CR845-Placebo n=21 participants at risk CR845 administered preoperatively and placebo administered postoperatively	CR845-No Postoperative Treatment n=7 participants at risk CR845 administered preoperatively and no study drug administered postoperatively	Placebo-No Postoperative Treatment n=13 participants at risk Placebo administered preoperatively and no study drug administered postoperatively
Injury, poisoning and procedural complications Post procedural haemorrhage	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	5.0% 1/20 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/21 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/7 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/13 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.
Injury, poisoning and procedural complications Anaemia Postoperative	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	1.4% 1/71 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/20 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/21 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/7 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/13 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.
Nervous system disorders Sedation	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	1.4% 1/71 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/20 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/21 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/7 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/13 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.
Nervous system disorders Somnolence	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/20 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/21 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	14.3% 1/7 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/13 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.
Psychiatric disorders Mental Status Changes	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	1.4% 1/71 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	5.0% 1/20 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/21 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/7 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/13 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.
Respiratory, thoracic and mediastinal disorders Pulmonary Embolism	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	1.4% 1/71 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/20 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/21 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/7 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/13 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.
Respiratory, thoracic and mediastinal disorders Respiratory Depression	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/20 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/21 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/7 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	7.7% 1/13 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.
Vascular disorders Deep Vein Thrombosis	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	1.4% 1/71 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/20 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/21 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/7 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/13 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.
Vascular disorders Hypovolaemic Shock	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	1.4% 1/71 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/20 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/21 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/7 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/13 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.
Cardiac disorders Tachycardia	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	1.4% 1/71 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/20 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/21 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/7 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/13 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.
Investigations Blood Sodium Increased	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	5.0% 1/20 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/21 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/7 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/13 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.
Musculoskeletal and connective tissue disorders Muscular Weakness	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/20 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/21 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	14.3% 1/7 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/13 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.
Reproductive system and breast disorders Endometriosis	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/20 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/21 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	14.3% 1/7 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/13 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.
Reproductive system and breast disorders Pelvic Adhesions	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/20 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/21 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	14.3% 1/7 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/13 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.

Other adverse events

Measure	Placebo-Placebo n=71 participants at risk Placebo administered both preoperatively and postoperatively	Placebo-CR845 n=71 participants at risk Placebo administered preoperatively and CR845 administered postoperatively	CR845-CR845 n=20 participants at risk CR845 administered both preoperatively and postoperatively	CR845-Placebo n=21 participants at risk CR845 administered preoperatively and placebo administered postoperatively	CR845-No Postoperative Treatment n=7 participants at risk CR845 administered preoperatively and no study drug administered postoperatively	Placebo-No Postoperative Treatment n=13 participants at risk Placebo administered preoperatively and no study drug administered postoperatively
Gastrointestinal disorders Nausea	53.5% 38/71 • Number of events 39 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	36.6% 26/71 • Number of events 26 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	45.0% 9/20 • Number of events 9 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	23.8% 5/21 • Number of events 5 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	14.3% 1/7 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	38.5% 5/13 • Number of events 5 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.
Gastrointestinal disorders Flatulence	25.4% 18/71 • Number of events 18 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	12.7% 9/71 • Number of events 9 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	5.0% 1/20 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	4.8% 1/21 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	14.3% 1/7 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	7.7% 1/13 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.
Gastrointestinal disorders Constipation	2.8% 2/71 • Number of events 2 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	15.5% 11/71 • Number of events 11 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	5.0% 1/20 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/21 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	14.3% 1/7 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	30.8% 4/13 • Number of events 4 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.
Gastrointestinal disorders Vomiting	4.2% 3/71 • Number of events 3 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	4.2% 3/71 • Number of events 3 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/20 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/21 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/7 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	30.8% 4/13 • Number of events 4 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.
Gastrointestinal disorders Abdominal Pain Lower	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/20 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/21 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	14.3% 1/7 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/13 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.
Gastrointestinal disorders Intestinal Dilatation	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/20 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/21 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/7 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	7.7% 1/13 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.
Vascular disorders Hypotension	19.7% 14/71 • Number of events 14 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	25.4% 18/71 • Number of events 18 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	20.0% 4/20 • Number of events 4 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	23.8% 5/21 • Number of events 5 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	28.6% 2/7 • Number of events 2 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	38.5% 5/13 • Number of events 5 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.
Vascular disorders Hypertension	2.8% 2/71 • Number of events 2 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	8.5% 6/71 • Number of events 6 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	5.0% 1/20 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/21 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	14.3% 1/7 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/13 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.
Nervous system disorders Headache	14.1% 10/71 • Number of events 10 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	12.7% 9/71 • Number of events 9 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	15.0% 3/20 • Number of events 3 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	14.3% 3/21 • Number of events 3 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/7 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	7.7% 1/13 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.
Nervous system disorders Dizziness	1.4% 1/71 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	2.8% 2/71 • Number of events 2 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	10.0% 2/20 • Number of events 2 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	4.8% 1/21 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	42.9% 3/7 • Number of events 3 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	7.7% 1/13 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.
Nervous system disorders Paraesthesia	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	15.0% 3/20 • Number of events 3 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	9.5% 2/21 • Number of events 2 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	57.1% 4/7 • Number of events 4 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/13 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hypoaesthesia	1.4% 1/71 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	1.4% 1/71 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/20 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/21 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	14.3% 1/7 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/13 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.
Nervous system disorders Somnolence	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/20 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/21 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	57.1% 4/7 • Number of events 5 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/13 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.
Nervous system disorders Sedation	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	1.4% 1/71 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/20 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/21 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	14.3% 1/7 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/13 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Dysstasia	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/20 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/21 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	14.3% 1/7 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/13 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.
Investigations Blood Sodium Increased	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	16.9% 12/71 • Number of events 12 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	35.0% 7/20 • Number of events 7 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	38.1% 8/21 • Number of events 8 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	14.3% 1/7 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/13 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.
Investigations Blood Chloride Increased	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	11.3% 8/71 • Number of events 8 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	30.0% 6/20 • Number of events 6 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	38.1% 8/21 • Number of events 8 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	14.3% 1/7 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/13 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.
Investigations Oxygen Saturation Decreased	1.4% 1/71 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	4.2% 3/71 • Number of events 3 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	5.0% 1/20 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/21 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/7 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	7.7% 1/13 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.
Investigations Airway Peak Pressure Increase	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/20 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/21 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/7 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	7.7% 1/13 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.
Investigations Gamma-Glutamyltransferase Increased	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/20 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/21 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/7 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	7.7% 1/13 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.
Investigations Urine Output Decreased	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/20 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/21 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	14.3% 1/7 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/13 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.
Renal and urinary disorders Urinary Retension	8.5% 6/71 • Number of events 7 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	11.3% 8/71 • Number of events 9 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	10.0% 2/20 • Number of events 2 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/21 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	14.3% 1/7 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/13 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.
Renal and urinary disorders Bladder Spasm	7.0% 5/71 • Number of events 5 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	2.8% 2/71 • Number of events 2 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/20 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/21 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/7 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/13 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.
Renal and urinary disorders Haematuria	1.4% 1/71 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/20 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/21 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	14.3% 1/7 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/13 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.
Renal and urinary disorders Polyuria	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	5.0% 1/20 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/21 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/7 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/13 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.
Renal and urinary disorders Micturition Urgency	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/20 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/21 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	14.3% 1/7 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/13 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.
Renal and urinary disorders Renal Failure Acute	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	5.0% 1/20 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/21 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/7 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/13 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.
Cardiac disorders Tachycardia	2.8% 2/71 • Number of events 2 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	9.9% 7/71 • Number of events 7 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/20 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	14.3% 3/21 • Number of events 3 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/7 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	7.7% 1/13 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.
Injury, poisoning and procedural complications Procedural Pain	2.8% 2/71 • Number of events 2 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	2.8% 2/71 • Number of events 2 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/20 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/21 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/7 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	15.4% 2/13 • Number of events 2 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.
Injury, poisoning and procedural complications Incisional Site Pain	1.4% 1/71 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/20 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/21 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	57.1% 4/7 • Number of events 4 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/13 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.
Injury, poisoning and procedural complications Post Procedural Haemorrhage	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	1.4% 1/71 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	5.0% 1/20 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	4.8% 1/21 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/7 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/13 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.
Respiratory, thoracic and mediastinal disorders Hypoxia	1.4% 1/71 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	8.5% 6/71 • Number of events 6 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	5.0% 1/20 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/21 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/7 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/13 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	5.0% 1/20 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/21 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/7 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/13 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.
Respiratory, thoracic and mediastinal disorders Atelectasis	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	5.0% 1/20 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/21 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/7 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/13 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.
Respiratory, thoracic and mediastinal disorders Respiratory Depression	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/20 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/21 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/7 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	7.7% 1/13 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.
Psychiatric disorders Insomnia	1.4% 1/71 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	5.6% 4/71 • Number of events 4 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/20 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	4.8% 1/21 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/7 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/13 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.
Psychiatric disorders Mental Status Change	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	1.4% 1/71 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	10.0% 2/20 • Number of events 2 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/21 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/7 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/13 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.
Skin and subcutaneous tissue disorders Pruritus	7.0% 5/71 • Number of events 5 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	4.2% 3/71 • Number of events 3 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	5.0% 1/20 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/21 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/7 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/13 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.
General disorders Pyrexia	1.4% 1/71 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	5.6% 4/71 • Number of events 4 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/20 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/21 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/7 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/13 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.
General disorders Chest Pain	1.4% 1/71 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/20 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/21 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	14.3% 1/7 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/13 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.
General disorders Sensation of Pressure	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	5.0% 1/20 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/21 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/7 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/13 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.
Metabolism and nutrition disorders Hypomagnesaemia	1.4% 1/71 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	2.8% 2/71 • Number of events 2 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	5.0% 1/20 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/21 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/7 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/13 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.
Metabolism and nutrition disorders Hypokalaemia	2.8% 2/71 • Number of events 2 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	5.0% 1/20 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/21 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/7 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/13 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.
Metabolism and nutrition disorders Hypophosphataemia	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	5.0% 1/20 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/21 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/7 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/13 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.
Infections and infestations Urinary tract Infection	1.4% 1/71 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	1.4% 1/71 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	5.0% 1/20 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/21 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/7 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/13 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.
Infections and infestations Cellulitis	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	5.0% 1/20 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/21 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/7 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/13 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.
Musculoskeletal and connective tissue disorders Back Pain	1.4% 1/71 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/20 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/21 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/7 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	7.7% 1/13 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.
Musculoskeletal and connective tissue disorders Limb Discomfort	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	5.0% 1/20 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/21 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/7 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/13 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.
Musculoskeletal and connective tissue disorders Muscule Spasm	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/20 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/21 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/7 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	7.7% 1/13 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.
Blood and lymphatic system disorders Anaemia	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	1.4% 1/71 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	5.0% 1/20 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	4.8% 1/21 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/7 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/13 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.
Eye disorders Diploplia	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	2.8% 2/71 • Number of events 2 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/20 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/21 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	14.3% 1/7 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/13 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.
Reproductive system and breast disorders Vulvovaginal Pruritus	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	1.4% 1/71 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/20 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/21 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/7 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	7.7% 1/13 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.
Reproductive system and breast disorders Breast Tenderness	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/20 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/21 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/7 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	7.7% 1/13 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.
Immune system disorders Hypersensitivity	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/71 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/20 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/21 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	0.00% 0/7 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.	7.7% 1/13 • Number of events 1 • Treatment-emergent adverse events were collected from the time the patient received her first dose of study drug through the Follow-up Visit.

Additional Information

Frédérique Menzaghi, PhD; Vice President, Research & Development

Cara Therapeutics

Phone: 203-567-1502

Email: fmenzaghi@caratherapeutics.com

Results disclosure agreements

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

Restriction type: GT60