Study of CA-008 (Vocacapsaicin) in Bunionectomy Patients

Study Overview
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Brief Summary
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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
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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 .

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

Conditions
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Post-surgical Pain

Intervention / Treatment
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* Drug: CA-008
* Drug: Placebo
* Drug: Ketorolac
* Drug: Acetaminophen
* Drug: Oxycodone
* Drug: Bupivacaine Hydrochloride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adult aged 18 - 75 years old American Society of Anesthesiology (ASA) physical Class 1, 2 or 3 Planning elective Bunionectomy repair For both males and females: using an acceptable method of birth control If a female: not pregnant or breastfeeding Have a body mass index ≤ 40 kg/m2. Be willing and able to sign the informed consent form (ICF) Be able to complete study procedures and pain scales and to communicate meaningfully in English Be willing to undergo 17 blood draws for pharmacokinetic (PK )assessments over 24 hours Exclusion Criteria: Have another painful condition, other than bunion-related pain, that may require pain treatment during the study period Have active skin disease or another abnormality at the anticipated site of surgery that could interfere with the planned surgery. Have a known allergy to chili peppers, capsaicin or the components of CA-008, bupivacaine HCl, ketorolac, acetaminophen or oxycodone. Have a history of significant medical, neuropsychiatric or other condition, including a clinically significant abnormal clinical laboratory test values Be on any medication not allowed per the protocol Within the past year have a history of illicit drug use or prescription medicine or alcohol abuse Have positive results on the alcohol test (breath or saliva) or urine drug screen Have previously participated in a clinical study with CA-008. Have participated in another clinical trial or used an investigational product within 30 days or five half-lives (whichever is longer)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: CA-008 (vocacapsaicin) 0.7 mg (0.05 mg/mL concentration)<br>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. | Drug: CA-008<br>* single-dose wound infiltration prior to surgical incision closure<br>* Other names: Vocacapsaicin;Drug: Ketorolac<br>* 30mg IV administered intraoperatively<br>Drug: Acetaminophen<br>* 1000mg IV administered intraoperatively<br>Drug: Oxycodone<br>* 5mg PO prn post-surgery<br>Drug: Bupivacaine Hydrochloride<br>* 0.5% infiltration pre-surgery<br>|
| Active Comparator: CA-008 (vocacapsaicin) 2.1 mg (0.15 mg/mL concentration)<br>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. | Drug: CA-008<br>* single-dose wound infiltration prior to surgical incision closure<br>* Other names: Vocacapsaicin;Drug: Ketorolac<br>* 30mg IV administered intraoperatively<br>Drug: Acetaminophen<br>* 1000mg IV administered intraoperatively<br>Drug: Oxycodone<br>* 5mg PO prn post-surgery<br>Drug: Bupivacaine Hydrochloride<br>* 0.5% infiltration pre-surgery<br>|
| Active Comparator: CA-008 (vocacapsaicin) 4.2 mg (0.3 mg/mL concentration)<br>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. | Drug: CA-008<br>* single-dose wound infiltration prior to surgical incision closure<br>* Other names: Vocacapsaicin;Drug: Ketorolac<br>* 30mg IV administered intraoperatively<br>Drug: Acetaminophen<br>* 1000mg IV administered intraoperatively<br>Drug: Oxycodone<br>* 5mg PO prn post-surgery<br>Drug: Bupivacaine Hydrochloride<br>* 0.5% infiltration pre-surgery<br>|
| Placebo Comparator: Placebo<br>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. | Drug: Placebo<br>* single-dose wound infiltration prior to surgical incision closure<br>Drug: Ketorolac<br>* 30mg IV administered intraoperatively<br>Drug: Acetaminophen<br>* 1000mg IV administered intraoperatively<br>Drug: Oxycodone<br>* 5mg PO prn post-surgery<br>Drug: Bupivacaine Hydrochloride<br>* 0.5% infiltration pre-surgery<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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: 96 hours] | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects Opioid Free | Percentage of subjects who are opioid-free for CA-008 compared to placebo. | [time frame: 96 hours] | 
| 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: 96 hours] |