Study in Subjects Undergoing Complete Abdominoplasty

Study Overview
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Brief Summary
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Phase 2, single center, randomized, double-blind, placebo-controlled, parallel design study of CA-008 vs. placebo in subjects undergoing an elective C-ABD under general anesthesia supplemented with a bupivacaine hydrochloride (HCl)transverse abdominis plane (TAP) block.

Detailed Description
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This is a Phase 2, single-center, randomized, double-blind, placebo-controlled, parallel design study evaluating up to 4 ascending dose level cohorts, each evaluating a single dose of CA-008 vs. placebo injected/instilled during an elective C-ABD. Up to 72 subjects may be randomized in 4 cohorts. For each subject, postsurgical assessments will be conducted in two parts: Inpatient period: starts with completion of study treatment injection (T0) and continues through 96 hours (T96h). Outpatient period: begins on discharge from the inpatient unit through various follow up visits to day 29 (D29)/week 4 (W4) after surgery. Note that additional follow up visits may occur at any time or even after D29/W4 to follow adverse events (AEs) to resolution or establishment of a new baseline.

Official Title
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A Phase 2, Randomized, Double-blind, Placebo-Controlled Efficacy, Pharmacokinetics and Safety Study of CA-008 in Subjects Undergoing Complete Abdominoplasty

Conditions
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Postsurgical Pain

Intervention / Treatment
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* Drug: CA-008 5 mg
* Drug: Placebo
* Drug: Bupivacaine Hydrochloride
* Drug: Hydromorphone
* Drug: Fentanyl
* Drug: Acetaminophen
* Drug: Oxycodone
* Drug: CA-008 10 mg
* Drug: CA-008 15 mg


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Plan to undergo an elective complete abdominoplasty (C-ABD), without collateral procedure or additional surgeries. In the medical judgment of the investigator, be a reasonably healthy adult aged 18 - 65 years old, inclusive, and American Society of Anesthesiology (ASA) physical Class 1 or 2 at the time of randomization. Unless the subject has a same sex partner, he or she must either be sterile (surgically or biologically) or commit to an acceptable method of birth control while participating in the study. Have a body mass index ≤ 35 kg/m². Be willing and able to sign the informed consent form (ICF) approved by an Institutional Review Board (IRB). Key Exclusion Criteria: In the opinion of the Investigator, have a concurrent painful condition that may require analgesic treatment during the study period or may confound post-surgical pain assessments. Have a known allergy to chili peppers, capsaicin or the components of CA-008, acetaminophen, bupivacaine, fentanyl hydromorphone or oxycodone. As determined by the investigator have a history or clinical manifestation of significant medical, neuropsychiatric or other condition, including a clinically significant existing arrhythmia, left bundle branch block or abnormal ECG, myocardial infarction or coronary arterial bypass graft surgery within the prior 12 months, significant abnormal clinical laboratory test value, or known bleeding abnormality that could preclude or impair study participation or interfere with study assessments. The following are considered disallowed medications: Be tolerant to opioids defined as those who have been receiving or have received chronic opioid therapy greater than 15 mg of oral morphine equivalents per day for greater than 3 out of 7 days per week over a one-month period within 6 months of screening. Within 1 day prior to surgery and throughout the inpatient period, be taking any capsaicin-containing products, such as dietary supplements or over-the-counter (OTC) preparations, including topical formulations, and prescription medications. Within the 7 days prior to surgery, be taking any central nervous system (CNS) active agent as an analgesic adjunct medication, such as anticonvulsants, antidepressants, benzodiazepines, sedative- hypnotics, clonidine and other central alpha-2 agents, ketamine or muscle relaxants. i. These drugs are permitted if prescribed for non-pain indications and the dose has been stable for at least 30 days prior to surgery. ii. The use of benzodiazepines and the non-benzodiazepines are permitted to treat insomnia during the postoperative period.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: CA-008 5 mg (0.05 mg/mL) Cohort 1<br>Cohort 1 (CA-008 5 mg): the surgery for each subject is to be performed under general anesthesia supplemented by a transverse abdominis plane (TAP) block and local surgical site infiltration. Prior to the surgery, perform the TAP block as a single injection of 0.25% bupivacaine hydrochloride (HCl) 60 mL (150 mg). | Drug: CA-008 5 mg<br>* 5 mg CA-008 reconstituted in saline.<br>* Other names: Vocacapsaicin;Drug: Bupivacaine Hydrochloride<br>* 0.25% administered pre-surgery<br>Drug: Hydromorphone<br>* 0.02 mg/kg IV administered intraoperatively<br>Drug: Fentanyl<br>* 100 mcg IV administered intraoperatively<br>Drug: Acetaminophen<br>* 1000 mg IV administered intraoperatively<br>Drug: Oxycodone<br>* 5-10 mg PO administered post-surgery<br>|
| Placebo Comparator: Placebo for Cohort 1<br>Cohort 1: Placebo comparator is identical in appearance to the investigational product, containing the same excipients as the active comparator. The surgery for each subject is to be performed under general anesthesia supplemented by a transverse abdominis plane (TAP) block and local surgical site infiltration. Prior to the surgery, perform the TAP block as a single injection of 0.25% bupivacaine hydrochloride (HCl) 60 mL (150 mg). | Drug: Placebo<br>* Each cohort will use placebo reconstituted in saline.<br>Drug: Bupivacaine Hydrochloride<br>* 0.25% administered pre-surgery<br>Drug: Hydromorphone<br>* 0.02 mg/kg IV administered intraoperatively<br>Drug: Fentanyl<br>* 100 mcg IV administered intraoperatively<br>Drug: Acetaminophen<br>* 1000 mg IV administered intraoperatively<br>Drug: Oxycodone<br>* 5-10 mg PO administered post-surgery<br>|
| Active Comparator: CA-008 10 mg (0.1 mg/mL)<br>Cohort 2 (CA-008 10 mg): the surgery is to be performed under general anesthesia supplemented by a transverse abdominis plane (TAP) block and local surgical site infiltration. Prior to the surgery, perform the TAP block as a single injection of 0.25% bupivacaine hydrochloride (HCl) 60 mL (150 mg). | Drug: Bupivacaine Hydrochloride<br>* 0.25% administered pre-surgery<br>Drug: Hydromorphone<br>* 0.02 mg/kg IV administered intraoperatively<br>Drug: Fentanyl<br>* 100 mcg IV administered intraoperatively<br>Drug: Acetaminophen<br>* 1000 mg IV administered intraoperatively<br>Drug: Oxycodone<br>* 5-10 mg PO administered post-surgery<br>Drug: CA-008 10 mg<br>* 10 mg CA-008 reconstituted in saline.<br>* Other names: Vocacapsaicin;|
| Active Comparator: CA-008 15 mg (0.15 mg/mL)<br>Cohort 3 (CA-008 15 mg): the surgery is to be performed under general anesthesia supplemented by a transverse abdominis plane (TAP) block and local surgical site infiltration. Prior to the surgery, perform the TAP block as a single injection of 0.25% bupivacaine hydrochloride (HCl) 60 mL (150 mg). | Drug: Bupivacaine Hydrochloride<br>* 0.25% administered pre-surgery<br>Drug: Hydromorphone<br>* 0.02 mg/kg IV administered intraoperatively<br>Drug: Fentanyl<br>* 100 mcg IV administered intraoperatively<br>Drug: Acetaminophen<br>* 1000 mg IV administered intraoperatively<br>Drug: Oxycodone<br>* 5-10 mg PO administered post-surgery<br>Drug: CA-008 15 mg<br>* 15 mg CA-008 reconstituted in saline.<br>* Other names: Vocacapsaicin;|
| Placebo Comparator: Placebo for Cohorts 2 and 3<br>Cohorts 2 & 3: Placebo comparator in each cohort is identical in appearance to the investigational product, containing the same excipients as the active comparator. The surgery for each subject is to be performed under general anesthesia supplemented by a transverse abdominis plane (TAP) block and local surgical site infiltration. Prior to the surgery, perform the TAP block as a single injection of 0.25% bupivacaine hydrochloride (HCl) 60 mL (150 mg). | Drug: Placebo<br>* Each cohort will use placebo reconstituted in saline.<br>Drug: Bupivacaine Hydrochloride<br>* 0.25% administered pre-surgery<br>Drug: Hydromorphone<br>* 0.02 mg/kg IV administered intraoperatively<br>Drug: Fentanyl<br>* 100 mcg IV administered intraoperatively<br>Drug: Acetaminophen<br>* 1000 mg IV administered intraoperatively<br>Drug: Oxycodone<br>* 5-10 mg PO administered post-surgery<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain Intensity Scores at 96 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 96 hours | 96 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weighted Sum of Pain Intensity (SPI) Assessments = AUC of NRS Scores | 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) from 0 to T96 hours | 0 to 96 hours | 
| Time to Opioid Cessation or Freedom | Time to the last use of opioid | From Surgery to Day 17 | 
| Percent of Opioid Free Subjects | Percent of subjects who were opioid free at 0-96 hours | 0 to 96 hours | 
| Total Opioid Consumption | The sum of daily opioid consumption (in morphine equivalents) | 0 to 96 hours |