BOTOX® Efficacy and Safety in the Treatment of Knee Osteoarthritis

Study Overview
=================
Brief Summary
-----------------
This study will evaluate the efficacy and safety of a single intra-articular injection of 2 doses of BOTOX® (onabotulinumtoxinA) compared with placebo as treatment for knee osteoarthritis symptoms.

Official Title
-----------------
BOTOX® Efficacy and Safety in the Treatment of Knee Osteoarthritis

Conditions
-----------------
Osteoarthritis

Intervention / Treatment
-----------------
* Biological: onabotulinumtoxinA
* Drug: Normal Saline


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Painful osteoarthritis Able to discontinue anti-inflammatory drugs and analgesics Must be ambulatory without assistive walking devices Exclusion Criteria: Chronic pain conditions other than knee osteoarthritis Treatment with corticosteroids in the study knee within 12 weeks Treatment with hyaluronic acid in the study knee within 24 weeks Previous treatment with any botulinum toxin for any reason Diagnosis of myasthenia gravis, Eaton-Lambert syndrome, or amyotrophic lateral sclerosis

Ages Eligible for Study
-----------------
Minimum Age: 40 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OnabotulinumtoxinA 400 U<br>OnabotulinumtoxinA 400 U injection into the intra-articular space of the study knee on Day 1. | Biological: onabotulinumtoxinA<br>* onabotulinumtoxinA (botulinum toxin Type A) injection into the intra-articular space of the study knee.<br>* Other names: BOTOX®;|
| Experimental: OnabotulinumtoxinA 200 U<br>OnabotulinumtoxinA 200 U injection into the intra-articular space of the study knee on Day 1. | Biological: onabotulinumtoxinA<br>* onabotulinumtoxinA (botulinum toxin Type A) injection into the intra-articular space of the study knee.<br>* Other names: BOTOX®;|
| Placebo Comparator: Placebo<br>Placebo (Normal Saline) injection into the intra-articular space of the study knee on Day 1. | Drug: Normal Saline<br>* Normal Saline (placebo) injection into the intra-articular space of the study knee.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the 7-Day Average Daily Pain Score Using an 11-Point Scale | Participants recorded the pain in their knee during the previous 24 hours in a daily diary where: 0=no pain to 10= worst pain possible. The daily pain scores over 7-days were averaged. A negative change from Baseline indicates improvement. | Baseline, Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC™) Pain Score Using an 11-Point Scale | The WOMAC Pain Score consisted of 5 questions about pain completed by the participant where: 0=no pain to 10=extreme pain for a total possible Pain Score of 0 (best) to 50 (worst). A negative change from Baseline indicates improvement. | Baseline, Weeks 1, 4, 8, 12, 16, 20 and 24 | 
| Change From Baseline in the WOMAC™ Physical Function Score Using an 11-Point Scale | The WOMAC Physical Function Score consisted of 17 questions about the difficulty of daily activities completed by the participant where: 0=no difficulty to 10=extreme difficulty for a total possible Physical Function Score of 0 (best) to 170 (worst). A negative change from Baseline indicates improvement. | Baseline, Weeks 1, 4, 8, 12, 16, 20 and 24 | 
| Patient Global Impression of Change (GIC) Using a 7-Point Scale | The participant rated the change in their health status since enrollment using a 7-point scale where: +3=very much improved, +2=much improved, +1=minimally improved, 0=no change, -1=minimally worse, -2=much worse and -3=very much worse. Negative scores indicate worsening and positive scores indicate improvement. | Weeks 1, 4, 8, 12, 16, 20 and 24 | 
| Change From Baseline in the 7-Day Average Daily Worst Pain Score Using an 11-Point Scale | Participants recorded the pain in their knee during the previous 24 hours in a daily diary where: 0=no pain to 10= worst pain possible. The daily worst pain scores over 7-days were averaged. A negative change from Baseline indicates improvement. | Baseline, Week 24 |