Postsurgical Pain
Conditions
Brief summary
In the pilot (Part A) of this study, multiple doses of CA-008 (vocacapsaicin) were evaluated for safety, tolerability, and PK. Doses were then selected for the expanded part (Part B) of the study, where CA-008 was compared to placebo. Patients had serial assessments of safety, PK, and drug effect.
Detailed description
Not provided
Interventions
DRUGCA-008
Local administration during surgery
DRUGPlacebo
Local administration during surgery
Sponsors
Concentric Analgesics
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Part A: dose ascending, placebo-controlled Part B: randomized, double-blind, placebo-controlled, parallel design
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Scheduled elective Total Knee Arthroplasty (TKA) under spinal anesthesia * Aged 18-80 years old * ASA physical class 1, 2, or 3 * BMI \</= 42 kg/m2 * Generally healthy
Exclusion criteria
* Concurrent condition requiring analgesic treatment during study period * Opioid tolerant * Known allergy to capsaicin or other study medication * Use of prohibited medications
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pain Intensity Scores | 0 to Day 15 post dose | 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. AUC is calculated using the standard trapezoidal rule from serial measures of NRS taken every 4 hours from 0-96 hours following surgery and twice daily from 96h to Day 15 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total Opioid Consumption | 0 to Day 15 post dose | CA-008 versus placebo comparison, total opioid consumption in oral morphine equivalents |
Countries
United States
Participant flow
Recruitment details
Part A consisted of 3 small, sequential, placebo-controlled, dose-escalation cohorts evaluating 36, 60 and 90 mg for safety. Part B evaluated 36 and 60 mg compared to placebo in parallel, randomized groups. Efficacy data from Part A remained blinded until the end of Part B and these data were pooled for analysis.
Pre-assignment details
Of the 193 enrolled participants, 193 met inclusion criteria and were randomized to treatment. 1 patient randomized to the 36 mg cohort and 1 patient randomized to the 60 mg cohort received placebo. These two patients were included in the placebo group. The efficacy and safety data from Parts A and B of the study are pooled by treatment group for the placebo, 30 mg and 60 mg treatment groups.
Participants by arm
| Arm | Count |
|---|---|
| CA-008 36 mg Single administration
CA-008: Local administration during surgery | 60 |
| CA-008 60 mg Single administration
CA-008: Local administration during surgery | 61 |
| CA-008 90 mg Single administration
CA-008: Local administration during surgery | 6 |
| Placebo Single administration
Placebo: Local administration during surgery | 66 |
| Total | 193 |
Baseline characteristics
| Characteristic | CA-008 36 mg | CA-008 60 mg | CA-008 90 mg | Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 63.9 years STANDARD_DEVIATION 7.79 | 63.1 years STANDARD_DEVIATION 7.82 | 65.5 years STANDARD_DEVIATION 8.92 | 59.7 years STANDARD_DEVIATION 6.45 | 62.3 years STANDARD_DEVIATION 7.59 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 11 Participants | 16 Participants | 0 Participants | 12 Participants | 39 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 49 Participants | 45 Participants | 5 Participants | 54 Participants | 153 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 5 Participants | 1 Participants | 1 Participants | 9 Participants |
| Race (NIH/OMB) Black or African American | 13 Participants | 10 Participants | 0 Participants | 9 Participants | 32 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 45 Participants | 45 Participants | 5 Participants | 56 Participants | 151 Participants |
| Sex: Female, Male Female | 29 Participants | 32 Participants | 4 Participants | 39 Participants | 104 Participants |
| Sex: Female, Male Male | 31 Participants | 29 Participants | 2 Participants | 27 Participants | 89 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 / 60 | 0 / 61 | 0 / 6 | 0 / 66 |
| other Total, other adverse events | 54 / 60 | 58 / 61 | 6 / 6 | 66 / 66 |
| serious Total, serious adverse events | 2 / 60 | 1 / 61 | 0 / 6 | 2 / 66 |
Outcome results
Primary
Pain Intensity Scores
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. AUC is calculated using the standard trapezoidal rule from serial measures of NRS taken every 4 hours from 0-96 hours following surgery and twice daily from 96h to Day 15
Time frame: 0 to Day 15 post dose
Population: 193 patients - Modified Intent-to-Treat~One patient who was randomized to CA-008 36 mg, but actually received Placebo is included in CA-008 36 mg.~One patient who was randomized to CA-008 60 mg, but actually received Placebo is included in CA-008 60 mg.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CA-008 36 mg (0.3 mg/mL Concentration) | Pain Intensity Scores | AUC 12-96 hour | 367.41 scores on a scale*hours | Standard Deviation 137.561 |
| CA-008 36 mg (0.3 mg/mL Concentration) | Pain Intensity Scores | AUC 0-Day 15 | 1235.36 scores on a scale*hours | Standard Deviation 608.259 |
| CA-008 36 mg (0.3 mg/mL Concentration) | Pain Intensity Scores | AUC 0-96 hour | 397.68 scores on a scale*hours | Standard Deviation 152.002 |
| CA-008 60 mg (0.5 mg/mL Concentration) | Pain Intensity Scores | AUC 12-96 hour | 415.27 scores on a scale*hours | Standard Deviation 140.967 |
| CA-008 60 mg (0.5 mg/mL Concentration) | Pain Intensity Scores | AUC 0-Day 15 | 1530.93 scores on a scale*hours | Standard Deviation 571.337 |
| CA-008 60 mg (0.5 mg/mL Concentration) | Pain Intensity Scores | AUC 0-96 hour | 448.02 scores on a scale*hours | Standard Deviation 155.948 |
| CA-008 90 mg (0.75 mg/mL Concentration) | Pain Intensity Scores | AUC 0-96 hour | 403.08 scores on a scale*hours | Standard Deviation 172.515 |
| CA-008 90 mg (0.75 mg/mL Concentration) | Pain Intensity Scores | AUC 12-96 hour | 373.92 scores on a scale*hours | Standard Deviation 175.834 |
| CA-008 90 mg (0.75 mg/mL Concentration) | Pain Intensity Scores | AUC 0-Day 15 | 1629.97 scores on a scale*hours | Standard Deviation 437.951 |
| Placebo | Pain Intensity Scores | AUC 12-96 hour | 447.05 scores on a scale*hours | Standard Deviation 108.596 |
| Placebo | Pain Intensity Scores | AUC 0-Day 15 | 1452.08 scores on a scale*hours | Standard Deviation 493.622 |
| Placebo | Pain Intensity Scores | AUC 0-96 hour | 481.97 scores on a scale*hours | Standard Deviation 120.535 |
p-value: 0.0004ANOVA
Secondary
Total Opioid Consumption
CA-008 versus placebo comparison, total opioid consumption in oral morphine equivalents
Time frame: 0 to Day 15 post dose
Population: 193 patients - Modified Intent-to-Treat One patient who was randomized to CA-008 36 mg, but actually received Placebo is included in CA-008 36 mg. One patient who was randomized to CA-008 60 mg, but actually received Placebo is included in CA-008 60 mg.~Opioid consumption (OC) in oral morphine equivalent dose (OME)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CA-008 36 mg (0.3 mg/mL Concentration) | Total Opioid Consumption | OC 0- Day 15 | 206.04 mg morphine equivalents | Standard Deviation 132.99 |
| CA-008 36 mg (0.3 mg/mL Concentration) | Total Opioid Consumption | OC0-96 hours | 154.795 mg morphine equivalents | Standard Deviation 85.95 |
| CA-008 36 mg (0.3 mg/mL Concentration) | Total Opioid Consumption | OC12-96 hours | 141.37 mg morphine equivalents | Standard Deviation 75.98 |
| CA-008 60 mg (0.5 mg/mL Concentration) | Total Opioid Consumption | OC 0- Day 15 | 275.07 mg morphine equivalents | Standard Deviation 155.14 |
| CA-008 60 mg (0.5 mg/mL Concentration) | Total Opioid Consumption | OC12-96 hours | 165.92 mg morphine equivalents | Standard Deviation 81.48 |
| CA-008 60 mg (0.5 mg/mL Concentration) | Total Opioid Consumption | OC0-96 hours | 183.74 mg morphine equivalents | Standard Deviation 89.74 |
| CA-008 90 mg (0.75 mg/mL Concentration) | Total Opioid Consumption | OC12-96 hours | 151.04 mg morphine equivalents | Standard Deviation 70.59 |
| CA-008 90 mg (0.75 mg/mL Concentration) | Total Opioid Consumption | OC 0- Day 15 | 263.54 mg morphine equivalents | Standard Deviation 138.11 |
| CA-008 90 mg (0.75 mg/mL Concentration) | Total Opioid Consumption | OC0-96 hours | 177.29 mg morphine equivalents | Standard Deviation 66.67 |
| Placebo | Total Opioid Consumption | OC0-96 hours | 219.94 mg morphine equivalents | Standard Deviation 88.19 |
| Placebo | Total Opioid Consumption | OC 0- Day 15 | 319.12 mg morphine equivalents | Standard Deviation 164.62 |
| Placebo | Total Opioid Consumption | OC12-96 hours | 206.26 mg morphine equivalents | Standard Deviation 82.11 |
p-value: <0.0001ANOVA
p-value: 0.0026ANOVA