Pain
Conditions
Brief summary
A Phase 2, open-label study of CA-008 to evaluate post-surgical pain control with CA-008.
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).
Interventions
DRUGCA-008
Drug: CA-008 4.2 mg reconstituted in saline
DRUGKetorolac
30 mg IV at the onset of anesthesia
DRUGAcetaminophen IV
1 g at the onset of anesthesia
DRUGFentanyl
100 mcg IV fentanyl administered at the onset of anesthesia and additional 50 mcg near the end of surgery
DRUGBupivacaine Hydrochloride
0.25% 30 mL (75 mg) prior to surgery
DRUGLidocaine HCl
1.5% 12 mL at the end of surgery
DRUGCelecoxib
200 mg PO bid each day postoperative
1 g postoperative
DRUGLidocaine Hydrochloride
2% 15 mL at the end of surgery
DRUGExparel
Bupivacaine liposome injection suspension
Sponsors
Concentric Analgesics
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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 |
| 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
| Measure | Time frame | Description |
|---|---|---|
| Opioid Consumption | 0-72 hours | Summary of opioid consumption in oral morphine equivalents |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| CA-008 (Vocacapsaicin) 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.
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 | 9 |
| CA-008 (Vocacapsaicin) Cohort 2 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 | 9 |
| CA-008 (Vocacapsaicin) Cohort 3 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 | 9 |
| Exparel 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 | 9 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 2 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | CA-008 (Vocacapsaicin) Cohort 1 | Total | Exparel | CA-008 (Vocacapsaicin) Cohort 3 | CA-008 (Vocacapsaicin) Cohort 2 |
|---|---|---|---|---|---|
| Age, Continuous | 49.1 years STANDARD_DEVIATION 9.96 | 45.05 years STANDARD_DEVIATION 9.65 | 52.8 years STANDARD_DEVIATION 6.72 | 35.2 years STANDARD_DEVIATION 12.71 | 43.1 years STANDARD_DEVIATION 9.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 16 Participants | 4 Participants | 6 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 20 Participants | 5 Participants | 3 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 10 Participants | 2 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 23 Participants | 7 Participants | 6 Participants | 4 Participants |
| Region of Enrollment United States | 9 participants | 36 participants | 9 participants | 9 participants | 9 participants |
| Sex: Female, Male Female | 7 Participants | 27 Participants | 5 Participants | 8 Participants | 7 Participants |
| Sex: Female, Male Male | 2 Participants | 9 Participants | 4 Participants | 1 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 9 | 0 / 9 | 0 / 9 |
| other Total, other adverse events | 1 / 9 | 4 / 9 | 5 / 9 | 5 / 9 |
| serious Total, serious adverse events | 0 / 9 | 0 / 9 | 0 / 9 | 0 / 9 |
Outcome results
Primary
Area Under the Curve (AUC) of Numerical Rating Scale (NRS) Scores (at Rest) Over 72h
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
Population: Safety population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CA-008 Cohort 1 | Area Under the Curve (AUC) of Numerical Rating Scale (NRS) Scores (at Rest) Over 72h | 72.30 score on a scale*hour | Standard Deviation 95.476 |
| CA-008 Cohort 2 | Area Under the Curve (AUC) of Numerical Rating Scale (NRS) Scores (at Rest) Over 72h | 66.24 score on a scale*hour | Standard Deviation 54.365 |
| CA-008 Cohort 3 | Area Under the Curve (AUC) of Numerical Rating Scale (NRS) Scores (at Rest) Over 72h | 203.76 score on a scale*hour | Standard Deviation 103.718 |
| Exparel | Area Under the Curve (AUC) of Numerical Rating Scale (NRS) Scores (at Rest) Over 72h | 306.58 score on a scale*hour | Standard Deviation 92.883 |
Primary
Pain Intensity Scores at 24 Hours at Rest Using Numerical Rating Scale (NRS)
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
Population: Safety population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CA-008 Cohort 1 | Pain Intensity Scores at 24 Hours at Rest Using Numerical Rating Scale (NRS) | 0.6 units on a scale | Standard Deviation 0.88 |
| CA-008 Cohort 2 | Pain Intensity Scores at 24 Hours at Rest Using Numerical Rating Scale (NRS) | 1.7 units on a scale | Standard Deviation 1.66 |
| CA-008 Cohort 3 | Pain Intensity Scores at 24 Hours at Rest Using Numerical Rating Scale (NRS) | 5.1 units on a scale | Standard Deviation 1.45 |
| Exparel | Pain Intensity Scores at 24 Hours at Rest Using Numerical Rating Scale (NRS) | 6.0 units on a scale | Standard Deviation 1 |
Primary
Pain Intensity Scores at 48 Hours at Rest Using Numerical Rating Scale (NRS)
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
Population: Safety population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CA-008 Cohort 1 | Pain Intensity Scores at 48 Hours at Rest Using Numerical Rating Scale (NRS) | 1.3 score on a scale | Standard Deviation 2.12 |
| CA-008 Cohort 2 | Pain Intensity Scores at 48 Hours at Rest Using Numerical Rating Scale (NRS) | 0.6 score on a scale | Standard Deviation 0.73 |
| CA-008 Cohort 3 | Pain Intensity Scores at 48 Hours at Rest Using Numerical Rating Scale (NRS) | 2.7 score on a scale | Standard Deviation 2.45 |
| Exparel | Pain Intensity Scores at 48 Hours at Rest Using Numerical Rating Scale (NRS) | 4.8 score on a scale | Standard Deviation 2.11 |
Primary
Pain Intensity Scores at 72 Hours at Rest Using Numerical Rating Scale (NRS)
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
Population: Safety population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CA-008 Cohort 1 | Pain Intensity Scores at 72 Hours at Rest Using Numerical Rating Scale (NRS) | 1.2 score on a scale | Standard Deviation 2.28 |
| CA-008 Cohort 2 | Pain Intensity Scores at 72 Hours at Rest Using Numerical Rating Scale (NRS) | 0.3 score on a scale | Standard Deviation 0.71 |
| CA-008 Cohort 3 | Pain Intensity Scores at 72 Hours at Rest Using Numerical Rating Scale (NRS) | 2.0 score on a scale | Standard Deviation 2.12 |
| Exparel | Pain Intensity Scores at 72 Hours at Rest Using Numerical Rating Scale (NRS) | 4.6 score on a scale | Standard Deviation 2.88 |
Secondary
Opioid Consumption
Summary of opioid consumption in oral morphine equivalents
Time frame: 0-72 hours
Population: Safety population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CA-008 Cohort 1 | Opioid Consumption | 10.83 mg morphine equivalents | Standard Deviation 27.33 |
| CA-008 Cohort 2 | Opioid Consumption | 3.33 mg morphine equivalents | Standard Deviation 6.61 |
| CA-008 Cohort 3 | Opioid Consumption | 38.33 mg morphine equivalents | Standard Deviation 26.9 |
| Exparel | Opioid Consumption | 80.83 mg morphine equivalents | Standard Deviation 66.95 |