Safety and Tolerability of 4975 in Patients Undergoing Arthroscopic Surgery to Repair the Rotator Cuff of the Shoulder

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the safety, tolerability and explore the efficacy of a single intraoperative injection of 4975 in patients undergoing arthroscopic surgery for rotator cuff repair of the shoulder

Detailed Description
-----------------
This is a multicenter, randomized, double-blind, placebo-controlled, two-stage exploratory study in patients undergoing arthroscopic rotator cuff repair surgery. Stage 1) Patients will be randomized to receive either 4975 or placebo. The dose of 4975 will be escalated in a protocolized manner based on safety and tolerability. Stage 2) Patients will be randomized in a 1:1 ratio to receive either the selected dose of 4975 or placebo. All patients will be observed in the hospital for at least two days following surgery for safety, tolerability, and efficacy assessments. In addition there will be two planned follow-up visits after hospital discharge.

Official Title
-----------------
A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Two-Stage Exploratory Study to Evaluate Safety, Tolerability, Efficacy, and Pharmacokinetics of Intraoperative Subacromial Injection With 4975 in Patients Undergoing Arthroscopic Rotator Cuff Repair of the Shoulder

Conditions
-----------------
Rotator Cuff Repair of the Shoulder

Intervention / Treatment
-----------------
* Drug: 4975 - Highly purified capsaicin
* Drug: 4975 - Highly purified capsaicin
* Drug: 4975 - Highly purified capsaicin
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Key Inclusion Criteria: Male or female between the ages of 18 and 75 inclusive In overall good health and planning to undergo unilateral arthroscopic shoulder surgery to repair at least one rotator cuff tendon involving humeral attachment Willing and able to complete the study procedures, pain assessments, and medication diaries, and to communicate in Korean or English with study personnel Key Exclusion Criteria: Shoulder surgery requiring concomitant repair of biceps muscle or associated tendon(s) Planning to undergo shoulder surgery on both shoulders Use of disallowed pain medications prior to the surgery Female patients who are pregnant or lactating or who plan to get pregnant Diabetes mellitus with a known HbA1C>9.5

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>4975 | Drug: 4975 - Highly purified capsaicin<br>* Solution, 0.5 mg, single dose, injection<br>* Other names: Adlea;|
| Experimental: 2<br>4975 | Drug: 4975 - Highly purified capsaicin<br>* Solution, 0.75 mg, single dose, injection<br>* Other names: Adlea;|
| Experimental: 3<br>4975 | Drug: 4975 - Highly purified capsaicin<br>* Solution, 0.1 mg, Single dose, injection<br>* Other names: Adlea;|
| Placebo Comparator: 4<br>Placebo | Drug: Placebo<br>* Solution, single dose, injection<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain intensity using a standard 11-point numerical rating system (NRS), which will be assessed at predefined times following surgery |  | 28 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean overall daily pain and worst daily pain. Pain intensity with physical therapy. Safety outcomes include ECG, vital signs, adverse drug reactions, and wound exams |  | 28 Days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Rotator cuff, Shoulder, Arthroscopic shoulder surgery