Postsurgical Pain
Conditions
Brief summary
A Three-Part, Phase 1/2, Randomized, Double-blind, Placebo-Controlled, Adaptive Safety, Pharmacokinetics, and Preliminary Efficacy Study of CA-008 (Vocacapsaicin) in Patients Undergoing Ventral Hernia Repair
Interventions
DRUGCA-008 (vocacapsaicin)
Single administration of CA-008 (vocacapsaicin) versus placebo
DRUGPlacebo
Single administration of CA-008 (vocacapsaicin) versus placebo
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 80 Years
Healthy volunteers
No
Inclusion criteria
* Scheduled elective, primary, open laparotomy with VHR, with retromuscular, preperitoneal mesh placement, with midline fascial reconstruction * ASA physical class 1, 2, or 3 * BMI \</= 40 kg/m2 * Aged 18-80 years old
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 at Rest - Part B | Up to 96 hours | Pain at rest measured by a Numeric Rating Scale (NRS) from time 0 to 96 hours (AUC 0-96). NRS pain scores at rest were collected at 1, 2, 4, 6, 8, 12, 16, 20, 24 and every 4 hours there after post the time of entry into the PACU (while the patient is awake), until discharge from the inpatient until at 96 hour. NRS area under the curve (AUC) is the weighted sum of current pain intensity assessments for a specified time interval. The NRS ranks pain from 0-10; zero being no pain present and 10 being the worst possible pain. Other than 0 and 10, no other pain ratings (2-9) were labeled. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evoked NRS - Part B | Up to 96 hours | Evoked NRS pain scores (three maneuvers: coughing, sitting up, walking) from time 0-96 hours. Evoked NRS scores were obtained twice daily in the morning at 10:00AM (± 1h) and in the afternoon at 4:00PM (±1 h). NRS area under the curve (AUC) is the weighted sum of current pain intensity assessments for a specified time interval. The NRS ranks pain from 0-10; zero being no pain present and 10 being the worst possible pain. Other than 0 and 10, no other pain ratings (2-9) were labeled. |
| Opioid Consumption - Part B | Up to Day 8 | Total opioid consumption (OC) converted to an oral morphine equivalent (OME) dose from 0 to 96 hours (OC 0-T96) and 0 to Day 8 (OC 0-D8). |
Countries
United States
Participant flow
Recruitment details
The clinical trial was conducted at one clinical research surgical center from September 2020 until June 2021. Qualified patients are adults aged 18 to 80 years of age, inclusive, who are planning to undergo an elective, open laparotomy for ventral hernia repair (VHR), with retromuscular, preperitoneal mesh repair and who otherwise meet eligibility criteria.
Pre-assignment details
Sixty-seven patients were screened. Ten met requirements for open-label Part A and 24 were randomized to Part B. Patients meeting all inclusion and no exclusion criteria underwent VHR surgery and dosing on Day 1. The patient was closely followed during the outpatient portion to Day 29 post surgery. Part A began enrolling in September 2020 and Part B on 10FEB2021. Part C was not conducted due to a corporate decision, and not due to any safety concerns.
Participants by arm
| Arm | Count |
|---|---|
| CA-008 (Vocacapsaicin), 15 mg - Part A Single administration of CA-008 (vocacapsaicin), 15 mg (50 ml of a 0.3 mg/mL solution) | 10 |
| CA-008 (Vocacapsaicin), 24 mg - Part B Single administration of CA-008 (vocacapsaicin), 24 mg (80 ml of a 0.3 mg/mL solution) | 12 |
| Placebo - Part B Single administration of placebo | 12 |
| Total | 34 |
Baseline characteristics
| Characteristic | CA-008 (Vocacapsaicin), 15 mg - Part A | CA-008 (Vocacapsaicin), 24 mg - Part B | Placebo - Part B | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 12 Participants | 12 Participants | 34 Participants |
| Age, Continuous | 47.9 years STANDARD_DEVIATION 10.8 | 47.1 years STANDARD_DEVIATION 10.16 | 42.2 years STANDARD_DEVIATION 10.19 | 45.6 years STANDARD_DEVIATION 10.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 8 Participants | 6 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants | 4 Participants | 6 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 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 |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 9 Participants | 12 Participants | 11 Participants | 32 Participants |
| Region of Enrollment United States | 10 participants | 12 participants | 12 participants | 34 participants |
| Sex: Female, Male Female | 2 Participants | 4 Participants | 3 Participants | 9 Participants |
| Sex: Female, Male Male | 8 Participants | 8 Participants | 9 Participants | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 9 / 10 | 10 / 12 | 10 / 12 |
| serious Total, serious adverse events | 0 / 10 | 0 / 12 | 0 / 12 |
Outcome results
Primary
Pain at Rest - Part B
Pain at rest measured by a Numeric Rating Scale (NRS) from time 0 to 96 hours (AUC 0-96). NRS pain scores at rest were collected at 1, 2, 4, 6, 8, 12, 16, 20, 24 and every 4 hours there after post the time of entry into the PACU (while the patient is awake), until discharge from the inpatient until at 96 hour. NRS area under the curve (AUC) is the weighted sum of current pain intensity assessments for a specified time interval. The NRS ranks pain from 0-10; zero being no pain present and 10 being the worst possible pain. Other than 0 and 10, no other pain ratings (2-9) were labeled.
Time frame: Up to 96 hours
Population: modified Intent to Treat (mITT) population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CA-008 (Vocacapsaicin), 24 mg - Part B | Pain at Rest - Part B | 148.98 score on a scale*hours | Standard Deviation 146.68 |
| Placebo - Part B | Pain at Rest - Part B | 188.26 score on a scale*hours | Standard Deviation 120.6 |
p-value: 0.481295% CI: [-152.97, 74.4]ANOVA
Secondary
Evoked NRS - Part B
Evoked NRS pain scores (three maneuvers: coughing, sitting up, walking) from time 0-96 hours. Evoked NRS scores were obtained twice daily in the morning at 10:00AM (± 1h) and in the afternoon at 4:00PM (±1 h). NRS area under the curve (AUC) is the weighted sum of current pain intensity assessments for a specified time interval. The NRS ranks pain from 0-10; zero being no pain present and 10 being the worst possible pain. Other than 0 and 10, no other pain ratings (2-9) were labeled.
Time frame: Up to 96 hours
Population: modified Intent to Treat (mITT) population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CA-008 (Vocacapsaicin), 24 mg - Part B | Evoked NRS - Part B | After ambulation | 143.42 score on a scale*hours | Standard Deviation 112.71 |
| CA-008 (Vocacapsaicin), 24 mg - Part B | Evoked NRS - Part B | Coughing | 187.58 score on a scale*hours | Standard Deviation 176.49 |
| CA-008 (Vocacapsaicin), 24 mg - Part B | Evoked NRS - Part B | Sitting-up | 116.24 score on a scale*hours | Standard Deviation 105.9 |
| Placebo - Part B | Evoked NRS - Part B | Coughing | 345.66 score on a scale*hours | Standard Deviation 135.5 |
| Placebo - Part B | Evoked NRS - Part B | After ambulation | 222.14 score on a scale*hours | Standard Deviation 94.89 |
| Placebo - Part B | Evoked NRS - Part B | Sitting-up | 171.28 score on a scale*hours | Standard Deviation 105.69 |
Comparison: Applies to evoked measure for after sitting up.p-value: 0.215895% CI: [-144.61, 34.53]ANOVA
Comparison: Applies to evoked measure of after ambulation.p-value: 0.077795% CI: [-166.93, 9.48]ANOVA
Comparison: Applies to evoked measure of after coughing.p-value: 0.022295% CI: [-291.29, -24.87]ANOVA
Secondary
Opioid Consumption - Part B
Total opioid consumption (OC) converted to an oral morphine equivalent (OME) dose from 0 to 96 hours (OC 0-T96) and 0 to Day 8 (OC 0-D8).
Time frame: Up to Day 8
Population: modified Intent to Treat (mITT) population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CA-008 (Vocacapsaicin), 24 mg - Part B | Opioid Consumption - Part B | OC 0 to 96 hours | 27.18 mg morphine equivalents | Standard Deviation 31.63 |
| CA-008 (Vocacapsaicin), 24 mg - Part B | Opioid Consumption - Part B | OC 0 to Day 8 | 29.68 mg morphine equivalents | Standard Deviation 37.66 |
| Placebo - Part B | Opioid Consumption - Part B | OC 0 to 96 hours | 36.56 mg morphine equivalents | Standard Deviation 30.7 |
| Placebo - Part B | Opioid Consumption - Part B | OC 0 to Day 8 | 37.81 mg morphine equivalents | Standard Deviation 33.27 |
Comparison: Applies to OC 0 - Day 8.p-value: 0.581195% CI: [-38.208, 21.958]ANOVA
Comparison: Entry applies to OC 0-96 hours.p-value: 0.46995% CI: [-35.764, 17.014]ANOVA