Study Evaluating the Safety, Efficacy and Pharmacokinetics of CA-008 (Vocacapsaicin)

Study Overview
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Brief Summary
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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
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Not provided

Official Title
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A Two-Part, Phase 1/2, Randomized, Double-blind, Placebo-Controlled, Adaptive Safety, Pharmacokinetics and Preliminary Efficacy Study of CA-008 in Patients Undergoing Total Knee Arthroplasy

Conditions
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Postsurgical Pain

Intervention / Treatment
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* Drug: CA-008
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Sequential Assignment
Interventional Model Description: Part A: dose ascending, placebo-controlled Part B: randomized, double-blind, placebo-controlled, parallel design
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: CA-008 36 mg<br>Single administration (0.3 mg/mL concentration) | Drug: CA-008<br>* Local administration during surgery<br>* Other names: vocacapsaicin;|
| Active Comparator: CA-008 60 mg<br>Single administration (0.5 mg/mL concentration) | Drug: CA-008<br>* Local administration during surgery<br>* Other names: vocacapsaicin;|
| Active Comparator: CA-008 90 mg<br>Single administration (0.75 mg/mL concentration) | Drug: CA-008<br>* Local administration during surgery<br>* Other names: vocacapsaicin;|
| Placebo Comparator: Placebo<br>Single administration | Drug: Placebo<br>* Local administration during surgery<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 0 to 192 hours post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Opioid Consumption | CA-008 versus placebo comparison, total opioid consumption in oral morphine equivalents | 0 to Day 15 post dose |