Open-Label CA-008 (Vocacapsaicin) in Bunionectomy

• Sponsor: Concentric Analgesics (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03885596
• Collaborator: (none)
• Enrollment: 36
• Location: 1
• Arms: 4
• Actual Duration (Months): 6.9
• Patients Per Site Per Month: 5.2

Study Details

Study Description

Brief Summary

A Phase 2, open-label study of CA-008 to evaluate post-surgical pain control with CA-008.

Condition or Disease	Intervention/Treatment	Phase
Pain	Drug: CA-008; Drug: Ketorolac; Drug: Acetaminophen IV; Drug: Fentanyl; Drug: Bupivacaine Hydrochloride; Drug: Lidocaine HCl; Drug: Celecoxib; Drug: Acetaminophen Oral; Drug: Lidocaine Hydrochloride; Drug: Exparel	Phase 2

Detailed Description

This is a Phase 2, single-center, open-label study evaluating a single dose of CA-008 4.2 mg administered with different standard-of-care anesthetic regimens during an elective unilateral transpositional first metatarsal osteotomy for the correction of hallux valgus deformity (bunionectomy).

Study Design

• Study Type: Interventional
• Actual Enrollment: 36 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label Study of Intraoperative CA-008 Administration in Subjects Undergoing Bunionectomy
• Actual Study Start Date: Mar 25, 2019
• Actual Primary Completion Date: Jul 2, 2019
• Actual Study Completion Date: Oct 22, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CA-008 Cohort 1 CA-008 4.2 mg reconstituted in saline All subjects received monitored anesthesia care (MAC) and a Mayo block followed by a sciatic (popliteal) nerve block.	Drug: CA-008; Drug: CA-008 4.2 mg reconstituted in saline; Other Names: Vocacapsaicin ; Drug: Ketorolac; 30 mg IV at the onset of anesthesia; Drug: Acetaminophen IV; 1 g at the onset of anesthesia; Drug: Fentanyl; 100 mcg IV fentanyl administered at the onset of anesthesia and additional 50 mcg near the end of surgery; Drug: Bupivacaine Hydrochloride; 0.25% 30 mL (75 mg) prior to surgery; Drug: Lidocaine HCl; 1.5% 12 mL at the end of surgery; Drug: Celecoxib; 200 mg PO bid each day postoperative; Drug: Acetaminophen Oral; 1 g postoperative
Experimental: CA-008 Cohort 2 CA-008 4.2 mg reconstituted in saline All subjects received monitored anesthesia care (MAC) and a Mayo block.	Drug: CA-008; Drug: CA-008 4.2 mg reconstituted in saline; Other Names: Vocacapsaicin ; Drug: Ketorolac; 30 mg IV at the onset of anesthesia; Drug: Acetaminophen IV; 1 g at the onset of anesthesia; Drug: Fentanyl; 100 mcg IV fentanyl administered at the onset of anesthesia and additional 50 mcg near the end of surgery; Drug: Bupivacaine Hydrochloride; 0.25% 30 mL (75 mg) prior to surgery; Drug: Celecoxib; 200 mg PO bid each day postoperative; Drug: Acetaminophen Oral; 1 g postoperative; Drug: Lidocaine Hydrochloride; 2% 15 mL at the end of surgery
Experimental: CA-008 Cohort 3 CA-008 4.2 mg reconstituted in saline All subjects received monitored anesthesia care (MAC) and a Mayo block.	Drug: CA-008; Drug: CA-008 4.2 mg reconstituted in saline; Other Names: Vocacapsaicin ; Drug: Ketorolac; 30 mg IV at the onset of anesthesia; Drug: Acetaminophen IV; 1 g at the onset of anesthesia; Drug: Fentanyl; 100 mcg IV fentanyl administered at the onset of anesthesia and additional 50 mcg near the end of surgery; Drug: Bupivacaine Hydrochloride; 0.25% 30 mL (75 mg) prior to surgery; Drug: Lidocaine Hydrochloride; 2% 15 mL at the end of surgery
Active Comparator: Exparel 106 mg [8 mL of the 133 mg/10 mL suspension] only All subjects received monitored anesthesia care (MAC) and a Mayo block.	Drug: Ketorolac; 30 mg IV at the onset of anesthesia; Drug: Acetaminophen IV; 1 g at the onset of anesthesia; Drug: Fentanyl; 100 mcg IV fentanyl administered at the onset of anesthesia and additional 50 mcg near the end of surgery; Drug: Bupivacaine Hydrochloride; 0.25% 30 mL (75 mg) prior to surgery; Drug: Lidocaine Hydrochloride; 2% 15 mL at the end of surgery; Drug: Exparel; Bupivacaine liposome injection suspension

Outcome Measures

Primary Outcome Measures

1. Area Under the Curve (AUC) of Numerical Rating Scale (NRS) Scores (at Rest) Over 72h [0-72 hours]

   Area Under the Curve of pain intensity scores (using a Numeric Rating Scale of pain intensity from 0-10 where 0 is no pain and 10 is the worst pain imaginable) over 72 hours

2. Pain Intensity Scores at 24 Hours at Rest Using Numerical Rating Scale (NRS) [24 hours]

   Numeric Rating Scale (NRS) of pain intensity from 0-10 where 0 is no pain and 10 is the worst pain imaginable at 24 hours

3. Pain Intensity Scores at 48 Hours at Rest Using Numerical Rating Scale (NRS) [48 hours]

   Numeric Rating Scale (NRS) of pain intensity from 0-10 where 0 is no pain and 10 is the worst pain imaginable at 48 hours

4. Pain Intensity Scores at 72 Hours at Rest Using Numerical Rating Scale (NRS) [72 hours]

   Numeric Rating Scale (NRS) of pain intensity from 0-10 where 0 is no pain and 10 is the worst pain imaginable at 72 hours

Secondary Outcome Measures

1. Opioid Consumption [0-72 hours]

   Summary of opioid consumption in oral morphine equivalents

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Healthy adult aged 18 - 65 years old

2. American Society of Anesthesiology (ASA) physical Class 1, 2 or 3

3. Planning elective Bunionectomy repair

4. For both males and females: using an acceptable method of birth control

5. If a female: not pregnant or breastfeeding

6. Have a body mass index ≤ 36 kg/m2

Exclusion Criteria:

1. Have another painful condition, other than bunion-related pain, that may require pain treatment during the study period

2. Have active skin disease or another abnormality at the anticipated site of surgery that could interfere with the planned surgery.

3. Have a known allergy to study medications.

4. Have a history of significant medical, neuropsychiatric or other condition, including a clinically significant abnormal clinical laboratory test values

5. Have positive results on the alcohol test (breath or saliva) or urine drug screen.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Lotus Clinical Research, LLC	Pasadena	California	United States	91105

Sponsors and Collaborators

• Concentric Analgesics

Investigators

• Study Director: Nancy Wu, Concentric Analgesics

Study Documents (Full-Text)

• Study Protocol - May 2, 2019
• Statistical Analysis Plan - Jun 5, 2019

More Information

Publications

None provided.

• Responsible Party: Concentric Analgesics
• ClinicalTrials.gov Identifier: NCT03885596
• Other Study ID Numbers: CA-PS-205
• First Posted: Mar 21, 2019
• Last Update Posted: Oct 27, 2021
• Last Verified: Sep 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Acetaminophen; Celecoxib; Ketorolac; Lidocaine; Fentanyl; Bupivacaine

Study Results

Participant Flow

Arm/Group Title	CA-008 Cohort 1	CA-008 Cohort 2	CA-008 Cohort 3	Exparel
Arm/Group Description	CA-008 4.2 mg All subjects received monitored anesthesia care (MAC) and a Mayo block followed by a sciatic (popliteal) nerve block. CA-008: Drug: CA-008 4.2 mg Ketorolac: 30 mg IV at the onset of anesthesia Acetaminophen IV: 1 g at the onset of anesthesia Fentanyl: 100 mcg IV fentanyl administered at the onset of anesthesia and additional 50 mcg near the end of surgery Bupivacaine Hydrochloride: 0.25% 30 mL (75 mg) prior to surgery Lidocaine HCl: 1.5% 12 mL at the end of surgery Celecoxib: 200 mg PO bid each day postoperative Acetaminophen Oral: 1 g postoperative	CA-008 4.2 mg All subjects received monitored anesthesia care (MAC) and a Mayo block. CA-008: Drug: CA-008 4.2 mg Ketorolac: 30 mg IV at the onset of anesthesia Acetaminophen IV: 1 g at the onset of anesthesia Fentanyl: 100 mcg IV fentanyl administered at the onset of anesthesia and additional 50 mcg near the end of surgery Bupivacaine Hydrochloride: 0.25% 30 mL (75 mg) prior to surgery Celecoxib: 200 mg PO bid each day postoperative Acetaminophen Oral: 1 g postoperative Lidocaine Hydrochloride: 2% 15 mL at the end of surgery	CA-008 4.2 mg All subjects received monitored anesthesia care (MAC) and a Mayo block. CA-008: Drug: CA-008 4.2 mg Ketorolac: 30 mg IV at the onset of anesthesia Acetaminophen IV: 1 g at the onset of anesthesia Fentanyl: 100 mcg IV fentanyl administered at the onset of anesthesia and additional 50 mcg near the end of surgery Bupivacaine Hydrochloride: 0.25% 30 mL (75 mg) prior to surgery Lidocaine Hydrochloride: 2% 15 mL at the end of surgery	106 mg [8 mL of the 133 mg/10 mL suspension] only All subjects received monitored anesthesia care (MAC) and a Mayo block. Ketorolac: 30 mg IV at the onset of anesthesia Acetaminophen IV: 1 g at the onset of anesthesia Fentanyl: 100 mcg IV fentanyl administered at the onset of anesthesia and additional 50 mcg near the end of surgery Bupivacaine Hydrochloride: 0.25% 30 mL (75 mg) prior to surgery Lidocaine Hydrochloride: 2% 15 mL at the end of surgery Exparel: Bupivacaine liposome injection suspension
Period Title: Overall Study
STARTED	9	9	9	9
COMPLETED	7	8	9	9
NOT COMPLETED	2	1	0	0

Baseline Characteristics

Arm/Group Title	CA-008 (Vocacapsaicin) Cohort 1	CA-008 (Vocacapsaicin) Cohort 2	CA-008 (Vocacapsaicin) Cohort 3	Exparel	Total
Arm/Group Description	CA-008 4.2 mg reconstituted in saline All subjects received monitored anesthesia care (MAC) and a Mayo block followed by a sciatic (popliteal) nerve block. CA-008: Drug: CA-008 4.2 mg reconstituted in saline Ketorolac: 30 mg IV at the onset of anesthesia Acetaminophen IV: 1 g at the onset of anesthesia Fentanyl: 100 mcg IV fentanyl administered at the onset of anesthesia and additional 50 mcg near the end of surgery Bupivacaine Hydrochloride: 0.25% 30 mL (75 mg) prior to surgery Lidocaine HCl: 1.5% 12 mL at the end of surgery Celecoxib: 200 mg PO bid each day postoperative Acetaminophen Oral: 1 g postoperative	CA-008 4.2 mg reconstituted in saline All subjects received monitored anesthesia care (MAC) and a Mayo block. CA-008: Drug: CA-008 4.2 mg reconstituted in saline Ketorolac: 30 mg IV at the onset of anesthesia Acetaminophen IV: 1 g at the onset of anesthesia Fentanyl: 100 mcg IV fentanyl administered at the onset of anesthesia and additional 50 mcg near the end of surgery Bupivacaine Hydrochloride: 0.25% 30 mL (75 mg) prior to surgery Celecoxib: 200 mg PO bid each day postoperative Acetaminophen Oral: 1 g postoperative Lidocaine Hydrochloride: 2% 15 mL at the end of surgery	CA-008 4.2 mg reconstituted in saline All subjects received monitored anesthesia care (MAC) and a Mayo block. CA-008: Drug: CA-008 4.2 mg reconstituted in saline Ketorolac: 30 mg IV at the onset of anesthesia Acetaminophen IV: 1 g at the onset of anesthesia Fentanyl: 100 mcg IV fentanyl administered at the onset of anesthesia and additional 50 mcg near the end of surgery Bupivacaine Hydrochloride: 0.25% 30 mL (75 mg) prior to surgery Lidocaine Hydrochloride: 2% 15 mL at the end of surgery	106 mg [8 mL of the 133 mg/10 mL suspension] only All subjects received monitored anesthesia care (MAC) and a Mayo block. Ketorolac: 30 mg IV at the onset of anesthesia Acetaminophen IV: 1 g at the onset of anesthesia Fentanyl: 100 mcg IV fentanyl administered at the onset of anesthesia and additional 50 mcg near the end of surgery Bupivacaine Hydrochloride: 0.25% 30 mL (75 mg) prior to surgery Lidocaine Hydrochloride: 2% 15 mL at the end of surgery Exparel: Bupivacaine liposome injection suspension	Total of all reporting groups
Overall Participants	9	9	9	9	36
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	49.1 (9.96)	43.1 (9.20)	35.2 (12.71)	52.8 (6.72)	45.05 (9.65)
Sex: Female, Male (Count of Participants)
Female	7 77.8%	7 77.8%	8 88.9%	5 55.6%	27 75%
Male	2 22.2%	2 22.2%	1 11.1%	4 44.4%	9 25%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	4 44.4%	2 22.2%	6 66.7%	4 44.4%	16 44.4%
Not Hispanic or Latino	5 55.6%	7 77.8%	3 33.3%	5 55.6%	20 55.6%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 11.1%	0 0%	0 0%	0 0%	1 2.8%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	1 11.1%	0 0%	1 2.8%
Black or African American	2 22.2%	4 44.4%	2 22.2%	2 22.2%	10 27.8%
White	6 66.7%	4 44.4%	6 66.7%	7 77.8%	23 63.9%
More than one race	0 0%	1 11.1%	0 0%	0 0%	1 2.8%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	9 100%	9 100%	9 100%	9 100%	36 100%

Outcome Measures

1. Primary Outcome

Title	Area Under the Curve (AUC) of Numerical Rating Scale (NRS) Scores (at Rest) Over 72h
Description	Area Under the Curve of pain intensity scores (using a Numeric Rating Scale of pain intensity from 0-10 where 0 is no pain and 10 is the worst pain imaginable) over 72 hours
Time Frame	0-72 hours

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	CA-008 Cohort 1	CA-008 Cohort 2	CA-008 Cohort 3	Exparel
Arm/Group Description	CA-008 4.2 mg reconstituted in saline All subjects received monitored anesthesia care (MAC) and a Mayo block followed by a sciatic (popliteal) nerve block. CA-008: Drug: CA-008 4.2 mg reconstituted in saline Ketorolac: 30 mg IV at the onset of anesthesia Acetaminophen IV: 1 g at the onset of anesthesia Fentanyl: 100 mcg IV fentanyl administered at the onset of anesthesia and additional 50 mcg near the end of surgery Bupivacaine Hydrochloride: 0.25% 30 mL (75 mg) prior to surgery Lidocaine HCl: 1.5% 12 mL at the end of surgery Celecoxib: 200 mg PO bid each day postoperative Acetaminophen Oral: 1 g postoperative	CA-008 4.2 mg reconstituted in saline All subjects received monitored anesthesia care (MAC) and a Mayo block. CA-008: Drug: CA-008 4.2 mg reconstituted in saline Ketorolac: 30 mg IV at the onset of anesthesia Acetaminophen IV: 1 g at the onset of anesthesia Fentanyl: 100 mcg IV fentanyl administered at the onset of anesthesia and additional 50 mcg near the end of surgery Bupivacaine Hydrochloride: 0.25% 30 mL (75 mg) prior to surgery Celecoxib: 200 mg PO bid each day postoperative Acetaminophen Oral: 1 g postoperative Lidocaine Hydrochloride: 2% 15 mL at the end of surgery	CA-008 4.2 mg reconstituted in saline All subjects received monitored anesthesia care (MAC) and a Mayo block. CA-008: Drug: CA-008 4.2 mg reconstituted in saline Ketorolac: 30 mg IV at the onset of anesthesia Acetaminophen IV: 1 g at the onset of anesthesia Fentanyl: 100 mcg IV fentanyl administered at the onset of anesthesia and additional 50 mcg near the end of surgery Bupivacaine Hydrochloride: 0.25% 30 mL (75 mg) prior to surgery Lidocaine Hydrochloride: 2% 15 mL at the end of surgery	106 mg [8 mL of the 133 mg/10 mL suspension] only All subjects received monitored anesthesia care (MAC) and a Mayo block. Ketorolac: 30 mg IV at the onset of anesthesia Acetaminophen IV: 1 g at the onset of anesthesia Fentanyl: 100 mcg IV fentanyl administered at the onset of anesthesia and additional 50 mcg near the end of surgery Bupivacaine Hydrochloride: 0.25% 30 mL (75 mg) prior to surgery Lidocaine Hydrochloride: 2% 15 mL at the end of surgery Exparel: Bupivacaine liposome injection suspension
Measure Participants	9	9	9	9
Mean (Standard Deviation) [score on a scale*hour]	72.30 (95.476)	66.24 (54.365)	203.76 (103.718)	306.58 (92.883)

2. Secondary Outcome

Title	Opioid Consumption
Description	Summary of opioid consumption in oral morphine equivalents
Time Frame	0-72 hours

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	CA-008 (Vocacapsaicin) Cohort 1	CA-008 (Vocacapsaicin) Cohort 2	CA-008 (Vocacapsaicin) Cohort 3	Exparel
Arm/Group Description	CA-008 4.2 mg reconstituted in saline All subjects received monitored anesthesia care (MAC) and a Mayo block followed by a sciatic (popliteal) nerve block. CA-008: Drug: CA-008 4.2 mg reconstituted in saline Ketorolac: 30 mg IV at the onset of anesthesia Acetaminophen IV: 1 g at the onset of anesthesia Fentanyl: 100 mcg IV fentanyl administered at the onset of anesthesia and additional 50 mcg near the end of surgery Bupivacaine Hydrochloride: 0.25% 30 mL (75 mg) prior to surgery Lidocaine HCl: 1.5% 12 mL at the end of surgery Celecoxib: 200 mg PO bid each day postoperative Acetaminophen Oral: 1 g postoperative	CA-008 4.2 mg reconstituted in saline All subjects received monitored anesthesia care (MAC) and a Mayo block. CA-008: Drug: CA-008 4.2 mg reconstituted in saline Ketorolac: 30 mg IV at the onset of anesthesia Acetaminophen IV: 1 g at the onset of anesthesia Fentanyl: 100 mcg IV fentanyl administered at the onset of anesthesia and additional 50 mcg near the end of surgery Bupivacaine Hydrochloride: 0.25% 30 mL (75 mg) prior to surgery Celecoxib: 200 mg PO bid each day postoperative Acetaminophen Oral: 1 g postoperative Lidocaine Hydrochloride: 2% 15 mL at the end of surgery	CA-008 4.2 mg reconstituted in saline All subjects received monitored anesthesia care (MAC) and a Mayo block. CA-008: Drug: CA-008 4.2 mg reconstituted in saline Ketorolac: 30 mg IV at the onset of anesthesia Acetaminophen IV: 1 g at the onset of anesthesia Fentanyl: 100 mcg IV fentanyl administered at the onset of anesthesia and additional 50 mcg near the end of surgery Bupivacaine Hydrochloride: 0.25% 30 mL (75 mg) prior to surgery Lidocaine Hydrochloride: 2% 15 mL at the end of surgery	106 mg [8 mL of the 133 mg/10 mL suspension] only All subjects received monitored anesthesia care (MAC) and a Mayo block. Ketorolac: 30 mg IV at the onset of anesthesia Acetaminophen IV: 1 g at the onset of anesthesia Fentanyl: 100 mcg IV fentanyl administered at the onset of anesthesia and additional 50 mcg near the end of surgery Bupivacaine Hydrochloride: 0.25% 30 mL (75 mg) prior to surgery Lidocaine Hydrochloride: 2% 15 mL at the end of surgery Exparel: Bupivacaine liposome injection suspension
Measure Participants	9	9	9	9
Mean (Standard Deviation) [mg morphine equivalents]	10.83 (27.33)	3.33 (6.61)	38.33 (26.90)	80.83 (66.95)

3. Primary Outcome

Title	Pain Intensity Scores at 24 Hours at Rest Using Numerical Rating Scale (NRS)
Description	Numeric Rating Scale (NRS) of pain intensity from 0-10 where 0 is no pain and 10 is the worst pain imaginable at 24 hours
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	CA-008 Cohort 1	CA-008 Cohort 2	CA-008 Cohort 3	Exparel
Arm/Group Description	CA-008 4.2 mg reconstituted in saline All subjects received monitored anesthesia care (MAC) and a Mayo block followed by a sciatic (popliteal) nerve block. CA-008: Drug: CA-008 4.2 mg reconstituted in saline Ketorolac: 30 mg IV at the onset of anesthesia Acetaminophen IV: 1 g at the onset of anesthesia Fentanyl: 100 mcg IV fentanyl administered at the onset of anesthesia and additional 50 mcg near the end of surgery Bupivacaine Hydrochloride: 0.25% 30 mL (75 mg) prior to surgery Lidocaine HCl: 1.5% 12 mL at the end of surgery Celecoxib: 200 mg PO bid each day postoperative Acetaminophen Oral: 1 g postoperative	CA-008 4.2 mg reconstituted in saline All subjects received monitored anesthesia care (MAC) and a Mayo block. CA-008: Drug: CA-008 4.2 mg reconstituted in saline Ketorolac: 30 mg IV at the onset of anesthesia Acetaminophen IV: 1 g at the onset of anesthesia Fentanyl: 100 mcg IV fentanyl administered at the onset of anesthesia and additional 50 mcg near the end of surgery Bupivacaine Hydrochloride: 0.25% 30 mL (75 mg) prior to surgery Celecoxib: 200 mg PO bid each day postoperative Acetaminophen Oral: 1 g postoperative Lidocaine Hydrochloride: 2% 15 mL at the end of surgery	CA-008 4.2 mg reconstituted in saline All subjects received monitored anesthesia care (MAC) and a Mayo block. CA-008: Drug: CA-008 4.2 mg reconstituted in saline Ketorolac: 30 mg IV at the onset of anesthesia Acetaminophen IV: 1 g at the onset of anesthesia Fentanyl: 100 mcg IV fentanyl administered at the onset of anesthesia and additional 50 mcg near the end of surgery Bupivacaine Hydrochloride: 0.25% 30 mL (75 mg) prior to surgery Lidocaine Hydrochloride: 2% 15 mL at the end of surgery	106 mg [8 mL of the 133 mg/10 mL suspension] only All subjects received monitored anesthesia care (MAC) and a Mayo block. Ketorolac: 30 mg IV at the onset of anesthesia Acetaminophen IV: 1 g at the onset of anesthesia Fentanyl: 100 mcg IV fentanyl administered at the onset of anesthesia and additional 50 mcg near the end of surgery Bupivacaine Hydrochloride: 0.25% 30 mL (75 mg) prior to surgery Lidocaine Hydrochloride: 2% 15 mL at the end of surgery Exparel: Bupivacaine liposome injection suspension
Measure Participants	9	9	9	9
Mean (Standard Deviation) [units on a scale]	0.6 (0.88)	1.7 (1.66)	5.1 (1.45)	6.0 (1.00)

4. Primary Outcome

Title	Pain Intensity Scores at 48 Hours at Rest Using Numerical Rating Scale (NRS)
Description	Numeric Rating Scale (NRS) of pain intensity from 0-10 where 0 is no pain and 10 is the worst pain imaginable at 48 hours
Time Frame	48 hours

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	CA-008 Cohort 1	CA-008 Cohort 2	CA-008 Cohort 3	Exparel
Arm/Group Description	CA-008 4.2 mg reconstituted in saline All subjects received monitored anesthesia care (MAC) and a Mayo block followed by a sciatic (popliteal) nerve block. CA-008: Drug: CA-008 4.2 mg reconstituted in saline Ketorolac: 30 mg IV at the onset of anesthesia Acetaminophen IV: 1 g at the onset of anesthesia Fentanyl: 100 mcg IV fentanyl administered at the onset of anesthesia and additional 50 mcg near the end of surgery Bupivacaine Hydrochloride: 0.25% 30 mL (75 mg) prior to surgery Lidocaine HCl: 1.5% 12 mL at the end of surgery Celecoxib: 200 mg PO bid each day postoperative Acetaminophen Oral: 1 g postoperative	CA-008 4.2 mg reconstituted in saline All subjects received monitored anesthesia care (MAC) and a Mayo block. CA-008: Drug: CA-008 4.2 mg reconstituted in saline Ketorolac: 30 mg IV at the onset of anesthesia Acetaminophen IV: 1 g at the onset of anesthesia Fentanyl: 100 mcg IV fentanyl administered at the onset of anesthesia and additional 50 mcg near the end of surgery Bupivacaine Hydrochloride: 0.25% 30 mL (75 mg) prior to surgery Celecoxib: 200 mg PO bid each day postoperative Acetaminophen Oral: 1 g postoperative Lidocaine Hydrochloride: 2% 15 mL at the end of surgery	CA-008 4.2 mg reconstituted in saline All subjects received monitored anesthesia care (MAC) and a Mayo block. CA-008: Drug: CA-008 4.2 mg reconstituted in saline Ketorolac: 30 mg IV at the onset of anesthesia Acetaminophen IV: 1 g at the onset of anesthesia Fentanyl: 100 mcg IV fentanyl administered at the onset of anesthesia and additional 50 mcg near the end of surgery Bupivacaine Hydrochloride: 0.25% 30 mL (75 mg) prior to surgery Lidocaine Hydrochloride: 2% 15 mL at the end of surgery	106 mg [8 mL of the 133 mg/10 mL suspension] only All subjects received monitored anesthesia care (MAC) and a Mayo block. Ketorolac: 30 mg IV at the onset of anesthesia Acetaminophen IV: 1 g at the onset of anesthesia Fentanyl: 100 mcg IV fentanyl administered at the onset of anesthesia and additional 50 mcg near the end of surgery Bupivacaine Hydrochloride: 0.25% 30 mL (75 mg) prior to surgery Lidocaine Hydrochloride: 2% 15 mL at the end of surgery Exparel: Bupivacaine liposome injection suspension
Measure Participants	9	9	9	9
Mean (Standard Deviation) [score on a scale]	1.3 (2.12)	0.6 (0.73)	2.7 (2.45)	4.8 (2.11)

5. Primary Outcome

Title	Pain Intensity Scores at 72 Hours at Rest Using Numerical Rating Scale (NRS)
Description	Numeric Rating Scale (NRS) of pain intensity from 0-10 where 0 is no pain and 10 is the worst pain imaginable at 72 hours
Time Frame	72 hours

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	CA-008 Cohort 1	CA-008 Cohort 2	CA-008 Cohort 3	Exparel
Arm/Group Description	CA-008 4.2 mg reconstituted in saline All subjects received monitored anesthesia care (MAC) and a Mayo block followed by a sciatic (popliteal) nerve block. CA-008: Drug: CA-008 4.2 mg reconstituted in saline Ketorolac: 30 mg IV at the onset of anesthesia Acetaminophen IV: 1 g at the onset of anesthesia Fentanyl: 100 mcg IV fentanyl administered at the onset of anesthesia and additional 50 mcg near the end of surgery Bupivacaine Hydrochloride: 0.25% 30 mL (75 mg) prior to surgery Lidocaine HCl: 1.5% 12 mL at the end of surgery Celecoxib: 200 mg PO bid each day postoperative Acetaminophen Oral: 1 g postoperative	CA-008 4.2 mg reconstituted in saline All subjects received monitored anesthesia care (MAC) and a Mayo block. CA-008: Drug: CA-008 4.2 mg reconstituted in saline Ketorolac: 30 mg IV at the onset of anesthesia Acetaminophen IV: 1 g at the onset of anesthesia Fentanyl: 100 mcg IV fentanyl administered at the onset of anesthesia and additional 50 mcg near the end of surgery Bupivacaine Hydrochloride: 0.25% 30 mL (75 mg) prior to surgery Celecoxib: 200 mg PO bid each day postoperative Acetaminophen Oral: 1 g postoperative Lidocaine Hydrochloride: 2% 15 mL at the end of surgery	CA-008 4.2 mg reconstituted in saline All subjects received monitored anesthesia care (MAC) and a Mayo block. CA-008: Drug: CA-008 4.2 mg reconstituted in saline Ketorolac: 30 mg IV at the onset of anesthesia Acetaminophen IV: 1 g at the onset of anesthesia Fentanyl: 100 mcg IV fentanyl administered at the onset of anesthesia and additional 50 mcg near the end of surgery Bupivacaine Hydrochloride: 0.25% 30 mL (75 mg) prior to surgery Lidocaine Hydrochloride: 2% 15 mL at the end of surgery	106 mg [8 mL of the 133 mg/10 mL suspension] only All subjects received monitored anesthesia care (MAC) and a Mayo block. Ketorolac: 30 mg IV at the onset of anesthesia Acetaminophen IV: 1 g at the onset of anesthesia Fentanyl: 100 mcg IV fentanyl administered at the onset of anesthesia and additional 50 mcg near the end of surgery Bupivacaine Hydrochloride: 0.25% 30 mL (75 mg) prior to surgery Lidocaine Hydrochloride: 2% 15 mL at the end of surgery Exparel: Bupivacaine liposome injection suspension
Measure Participants	9	9	9	9
Mean (Standard Deviation) [score on a scale]	1.2 (2.28)	0.3 (0.71)	2.0 (2.12)	4.6 (2.88)

Adverse Events

Time Frame	Up to 76 days: Screening period from 45 days prior to surgery (D-45) to D29±2 Study Completion Visit. Unscheduled visits or visits after D29 might be necessary to assess ongoing safety issues or to follow an event to resolution or to establishment of a new baseline.
Arm/Group Title	CA-008 Cohort 1		CA-008 Cohort 2		CA-008 Cohort 3		Exparel
Arm/Group Description	CA-008 4.2 mg reconstituted in saline All subjects received monitored anesthesia care (MAC) and a Mayo block followed by a sciatic (popliteal) nerve block. CA-008: Drug: CA-008 4.2 mg reconstituted in saline Ketorolac: 30 mg IV at the onset of anesthesia Acetaminophen IV: 1 g at the onset of anesthesia Fentanyl: 100 mcg IV fentanyl administered at the onset of anesthesia and additional 50 mcg near the end of surgery Bupivacaine Hydrochloride: 0.25% 30 mL (75 mg) prior to surgery Lidocaine HCl: 1.5% 12 mL at the end of surgery Celecoxib: 200 mg PO bid each day postoperative Acetaminophen Oral: 1 g postoperative		CA-008 4.2 mg reconstituted in saline All subjects received monitored anesthesia care (MAC) and a Mayo block. CA-008: Drug: CA-008 4.2 mg reconstituted in saline Ketorolac: 30 mg IV at the onset of anesthesia Acetaminophen IV: 1 g at the onset of anesthesia Fentanyl: 100 mcg IV fentanyl administered at the onset of anesthesia and additional 50 mcg near the end of surgery Bupivacaine Hydrochloride: 0.25% 30 mL (75 mg) prior to surgery Celecoxib: 200 mg PO bid each day postoperative Acetaminophen Oral: 1 g postoperative Lidocaine Hydrochloride: 2% 15 mL at the end of surgery		CA-008 4.2 mg reconstituted in saline All subjects received monitored anesthesia care (MAC) and a Mayo block. CA-008: Drug: CA-008 4.2 mg reconstituted in saline Ketorolac: 30 mg IV at the onset of anesthesia Acetaminophen IV: 1 g at the onset of anesthesia Fentanyl: 100 mcg IV fentanyl administered at the onset of anesthesia and additional 50 mcg near the end of surgery Bupivacaine Hydrochloride: 0.25% 30 mL (75 mg) prior to surgery Lidocaine Hydrochloride: 2% 15 mL at the end of surgery		106 mg [8 mL of the 133 mg/10 mL suspension] only All subjects received monitored anesthesia care (MAC) and a Mayo block. Ketorolac: 30 mg IV at the onset of anesthesia Acetaminophen IV: 1 g at the onset of anesthesia Fentanyl: 100 mcg IV fentanyl administered at the onset of anesthesia and additional 50 mcg near the end of surgery Bupivacaine Hydrochloride: 0.25% 30 mL (75 mg) prior to surgery Lidocaine Hydrochloride: 2% 15 mL at the end of surgery Exparel: Bupivacaine liposome injection suspension
All Cause Mortality
	CA-008 Cohort 1		CA-008 Cohort 2		CA-008 Cohort 3		Exparel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/9 (0%)		0/9 (0%)		0/9 (0%)		0/9 (0%)
Serious Adverse Events
	CA-008 Cohort 1		CA-008 Cohort 2		CA-008 Cohort 3		Exparel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/9 (0%)		0/9 (0%)		0/9 (0%)		0/9 (0%)
Other (Not Including Serious) Adverse Events
	CA-008 Cohort 1		CA-008 Cohort 2		CA-008 Cohort 3		Exparel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/9 (11.1%)		4/9 (44.4%)		5/9 (55.6%)		5/9 (55.6%)
Gastrointestinal disorders
Constipation	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	3/9 (33.3%)	3
Diarrhoea	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	1/9 (11.1%)	1
Nausea	0/9 (0%)	0	1/9 (11.1%)	1	1/9 (11.1%)	1	1/9 (11.1%)	1
Vomiting	0/9 (0%)	0	0/9 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0
Infections and infestations
Gastroenteritis	0/9 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0	0/9 (0%)	0
Injury, poisoning and procedural complications
Incision site pain	1/9 (11.1%)	1	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Procedural pain	0/9 (0%)	0	0/9 (0%)	0	3/9 (33.3%)	3	0/9 (0%)	0
Nervous system disorders
Dizziness	0/9 (0%)	0	0/9 (0%)	0	1/9 (11.1%)	1	1/9 (11.1%)	1
Headache	0/9 (0%)	0	1/9 (11.1%)	1	1/9 (11.1%)	1	1/9 (11.1%)	1
Sensory disturbance	1/9 (11.1%)	1	1/9 (11.1%)	1	0/9 (0%)	0	0/9 (0%)	0
Tension headache	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	1/9 (11.1%)	1
Skin and subcutaneous tissue disorders
Pruritus	0/9 (0%)	0	0/9 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0
Vascular disorders
Hypertension	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	1/9 (11.1%)	1

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.