Post-surgical Pain
Conditions
Brief summary
This is a Phase 2, multi-center, randomized, double-blind, placebo-controlled, parallel design study evaluating a single dose of one of three CA-008 dose levels vs. placebo injected during an elective bunionectomy Bunionectomy to assess post-surgical pain management and the need for rescue medication (oxycodone).
Detailed description
Primary Objective: To evaluate the efficacy of a single intraoperative administration of CA- 008 vs placebo in subjects undergoing an elective Bunionectomy . Secondary Objectives * To evaluate the safety and tolerability of a single intraoperative administration of CA-008 vs. placebo in subjects undergoing an elective Bunionectomy. * To evaluate the PK profile of a single intraoperative administration of CA-008 vs. placebo in subjects undergoing an elective Bunionectomy . * To explore the efficacy of various doses of CA-008 administered intraoperatively in subjects undergoing an elective Bunionectomy .
Interventions
DRUGCA-008
single-dose wound infiltration prior to surgical incision closure
DRUGPlacebo
single-dose wound infiltration prior to surgical incision closure
DRUGKetorolac
30mg IV administered intraoperatively
DRUGAcetaminophen
1000mg IV administered intraoperatively
DRUGOxycodone
5mg PO prn post-surgery
DRUGBupivacaine Hydrochloride
0.5% infiltration pre-surgery
Sponsors
Concentric Analgesics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Healthy adult aged 18 - 75 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 ≤ 40 kg/m2. 7. Be willing and able to sign the informed consent form (ICF) 8. Be able to complete study procedures and pain scales and to communicate meaningfully in English 9. Be willing to undergo 17 blood draws for pharmacokinetic (PK )assessments over 24 hours
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 chili peppers, capsaicin or the components of CA-008, bupivacaine HCl, ketorolac, acetaminophen or oxycodone. 4. Have a history of significant medical, neuropsychiatric or other condition, including a clinically significant abnormal clinical laboratory test values 5. Be on any medication not allowed per the protocol 6. Within the past year have a history of illicit drug use or prescription medicine or alcohol abuse 7. Have positive results on the alcohol test (breath or saliva) or urine drug screen 8. Have previously participated in a clinical study with CA-008. 9. Have participated in another clinical trial or used an investigational product within 30 days or five half-lives (whichever is longer)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Postsurgical Pain Based on the Weighted Sum of Pain Intensity (SPI) Assessments Over 96 Hours of the NRS Scores = Area Under the Curve (AUC) | [time frame: 96 hours] | Mean area under the curve (AUC) of the Numeric Rating Scale (NRS) weighted sum of pain intensity scores (at rest) from 0-10 where 0 is no pain and 10 is the worst pain imaginable for CA-008 compared to placebo. The time was collected 0 to 96 hours post-dose |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects Opioid Free | [time frame: 96 hours] | Percentage of subjects who are opioid-free for CA-008 compared to placebo. |
| Total Opioid Consumption (in Daily Morphine Equivalents) | [time frame: 96 hours] | Mean total postoperative opioid consumption (in daily oral morphine equivalents) for CA-008 compared to placebo |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| CA-008 0.7 mg (0.05 mg/mL Concentration) Each patient will receive a single dose of 0.7 mg CA-008 injected during an elective Bunionectomy with a multimodal analgesia regimen including a Nonsteroidal anti-inflammatory drug (NSAID) and regional Mayo block with bupivacaine.
CA-008: single-dose wound infiltration prior to surgical incision closure
Ketorolac: 30mg IV administered intraoperatively
Acetaminophen: 1000mg IV administered intraoperatively
Oxycodone: 5mg PO prn post-surgery
Bupivacaine Hydrochloride: 0.5% infiltration pre-surgery | 36 |
| CA-008 2.1 mg (0.15 mg/mL Concentration) Each patient will receive a single dose of 2.1 mg CA-008 injected during an elective Bunionectomy with a multimodal analgesia regimen including a Nonsteroidal anti-inflammatory drug (NSAID) and regional Mayo block with bupivacaine.
CA-008: single-dose wound infiltration prior to surgical incision closure
Ketorolac: 30mg IV administered intraoperatively
Acetaminophen: 1000mg IV administered intraoperatively
Oxycodone: 5mg PO prn post-surgery
Bupivacaine Hydrochloride: 0.5% infiltration pre-surgery | 36 |
| CA-008 4.2 mg (0.3 mg/mL Concentration) Each patient will receive a single dose of 4.2 mg CA-008 injected during an elective Bunionectomy with a multimodal analgesia regimen including a Nonsteroidal anti-inflammatory drug (NSAID) and regional Mayo block with bupivacaine.
CA-008: single-dose wound infiltration prior to surgical incision closure
Ketorolac: 30mg IV administered intraoperatively
Acetaminophen: 1000mg IV administered intraoperatively
Oxycodone: 5mg PO prn post-surgery
Bupivacaine Hydrochloride: 0.5% infiltration pre-surgery | 38 |
| Placebo Each patient will receive a single dose of CA-008 vehicle (identical to active treatment but without CA-008) injected during an elective Bunionectomy with a multimodal analgesia regimen including a Nonsteroidal anti-inflammatory drug (NSAID) and regional Mayo block with bupivacaine.
Placebo: single-dose wound infiltration prior to surgical incision closure
Ketorolac: 30mg IV administered intraoperatively
Acetaminophen: 1000mg IV administered intraoperatively
Oxycodone: 5mg PO prn post-surgery
Bupivacaine Hydrochloride: 0.5% infiltration pre-surgery | 37 |
| Total | 147 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lack of Efficacy | 0 | 0 | 1 | 2 |
| Overall Study | Lost to Follow-up | 1 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | CA-008 0.7 mg (0.05 mg/mL Concentration) | CA-008 2.1 mg (0.15 mg/mL Concentration) | CA-008 4.2 mg (0.3 mg/mL Concentration) | Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 48.9 years STANDARD_DEVIATION 12.29 | 44.6 years STANDARD_DEVIATION 12.33 | 41.4 years STANDARD_DEVIATION 12.16 | 50.7 years STANDARD_DEVIATION 12.46 | 46.4 years STANDARD_DEVIATION 12.73 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants | 11 Participants | 8 Participants | 12 Participants | 39 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 28 Participants | 25 Participants | 30 Participants | 25 Participants | 108 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 | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 12 Participants | 12 Participants | 14 Participants | 14 Participants | 52 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 3 Participants | 2 Participants | 0 Participants | 8 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 20 Participants | 20 Participants | 19 Participants | 22 Participants | 81 Participants |
| Region of Enrollment United States | 36 Participants | 36 Participants | 38 Participants | 37 Participants | 147 Participants |
| Sex: Female, Male Female | 33 Participants | 25 Participants | 34 Participants | 31 Participants | 123 Participants |
| Sex: Female, Male Male | 3 Participants | 11 Participants | 4 Participants | 6 Participants | 24 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 / 36 | 0 / 36 | 0 / 38 | 0 / 37 |
| other Total, other adverse events | 27 / 36 | 28 / 36 | 26 / 38 | 25 / 37 |
| serious Total, serious adverse events | 0 / 36 | 0 / 36 | 0 / 38 | 1 / 37 |
Outcome results
Primary
Change in Postsurgical Pain Based on the Weighted Sum of Pain Intensity (SPI) Assessments Over 96 Hours of the NRS Scores = Area Under the Curve (AUC)
Mean area under the curve (AUC) of the Numeric Rating Scale (NRS) weighted sum of pain intensity scores (at rest) from 0-10 where 0 is no pain and 10 is the worst pain imaginable for CA-008 compared to placebo. The time was collected 0 to 96 hours post-dose
Time frame: [time frame: 96 hours]
Population: Modified Intent to Treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CA-008 0.7 mg (0.05 mg/mL Concentration) | Change in Postsurgical Pain Based on the Weighted Sum of Pain Intensity (SPI) Assessments Over 96 Hours of the NRS Scores = Area Under the Curve (AUC) | 317.09 scores on a scale*hour | Standard Deviation 204.291 |
| CA-008 2.1 mg (0.15 mg/mL Concentration) | Change in Postsurgical Pain Based on the Weighted Sum of Pain Intensity (SPI) Assessments Over 96 Hours of the NRS Scores = Area Under the Curve (AUC) | 321.72 scores on a scale*hour | Standard Deviation 165.145 |
| CA-008 4.2 mg (0.3 mg/mL Concentration) | Change in Postsurgical Pain Based on the Weighted Sum of Pain Intensity (SPI) Assessments Over 96 Hours of the NRS Scores = Area Under the Curve (AUC) | 266.86 scores on a scale*hour | Standard Deviation 220.674 |
| Placebo | Change in Postsurgical Pain Based on the Weighted Sum of Pain Intensity (SPI) Assessments Over 96 Hours of the NRS Scores = Area Under the Curve (AUC) | 400.56 scores on a scale*hour | Standard Deviation 215.471 |
p-value: 0.005ANOVA
Secondary
Percentage of Subjects Opioid Free
Percentage of subjects who are opioid-free for CA-008 compared to placebo.
Time frame: [time frame: 96 hours]
Population: Modified Intent to Treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CA-008 0.7 mg (0.05 mg/mL Concentration) | Percentage of Subjects Opioid Free | 19.4 percentage of subjects |
| CA-008 2.1 mg (0.15 mg/mL Concentration) | Percentage of Subjects Opioid Free | 16.7 percentage of subjects |
| CA-008 4.2 mg (0.3 mg/mL Concentration) | Percentage of Subjects Opioid Free | 26.3 percentage of subjects |
| Placebo | Percentage of Subjects Opioid Free | 5.4 percentage of subjects |
p-value: 0.0245Regression, Logistic
Secondary
Total Opioid Consumption (in Daily Morphine Equivalents)
Mean total postoperative opioid consumption (in daily oral morphine equivalents) for CA-008 compared to placebo
Time frame: [time frame: 96 hours]
Population: Modified Intent to Treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CA-008 0.7 mg (0.05 mg/mL Concentration) | Total Opioid Consumption (in Daily Morphine Equivalents) | 42.50 mg morphine equivalents/day | Standard Deviation 38.074 |
| CA-008 2.1 mg (0.15 mg/mL Concentration) | Total Opioid Consumption (in Daily Morphine Equivalents) | 37.71 mg morphine equivalents/day | Standard Deviation 39.34 |
| CA-008 4.2 mg (0.3 mg/mL Concentration) | Total Opioid Consumption (in Daily Morphine Equivalents) | 28.22 mg morphine equivalents/day | Standard Deviation 28.355 |
| Placebo | Total Opioid Consumption (in Daily Morphine Equivalents) | 56.11 mg morphine equivalents/day | Standard Deviation 45.447 |
p-value: 0.0019ANOVA