Trial Outcomes & Findings for BOTOX® Efficacy and Safety in the Treatment of Knee Osteoarthritis (NCT NCT02230956)
NCT ID: NCT02230956
Last Updated: 2017-05-31
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
176 participants
Primary outcome timeframe
Baseline, Week 8
Results posted on
2017-05-31
Participant Flow
Participant milestones
| Measure |
OnabotulinumtoxinA 400 U
OnabotulinumtoxinA 400 U injection into the intra-articular space of the study knee on Day 1.
|
OnabotulinumtoxinA 200 U
OnabotulinumtoxinA 200 U injection into the intra-articular space of the study knee on Day 1.
|
Placebo
Placebo (Normal Saline) injection into the intra-articular space of the study knee on Day 1.
|
|---|---|---|---|
|
Overall Study
STARTED
|
44
|
43
|
89
|
|
Overall Study
COMPLETED
|
39
|
37
|
82
|
|
Overall Study
NOT COMPLETED
|
5
|
6
|
7
|
Reasons for withdrawal
| Measure |
OnabotulinumtoxinA 400 U
OnabotulinumtoxinA 400 U injection into the intra-articular space of the study knee on Day 1.
|
OnabotulinumtoxinA 200 U
OnabotulinumtoxinA 200 U injection into the intra-articular space of the study knee on Day 1.
|
Placebo
Placebo (Normal Saline) injection into the intra-articular space of the study knee on Day 1.
|
|---|---|---|---|
|
Overall Study
Adverse Event
|
1
|
1
|
0
|
|
Overall Study
Lack of Efficacy
|
1
|
1
|
1
|
|
Overall Study
Lost to Follow-up
|
1
|
1
|
2
|
|
Overall Study
Personal Reasons
|
2
|
1
|
1
|
|
Overall Study
Protocol Violation
|
0
|
1
|
1
|
|
Overall Study
Other Miscellaneous Reason
|
0
|
1
|
2
|
Baseline Characteristics
BOTOX® Efficacy and Safety in the Treatment of Knee Osteoarthritis
Baseline characteristics by cohort
| Measure |
OnabotulinumtoxinA 400 U
n=44 Participants
OnabotulinumtoxinA 400 U injection into the intra-articular space of the study knee on Day 1.
|
OnabotulinumtoxinA 200 U
n=43 Participants
OnabotulinumtoxinA 200 U injection into the intra-articular space of the study knee on Day 1.
|
Placebo
n=89 Participants
Placebo (Normal Saline) injection into the intra-articular space of the study knee on Day 1.
|
Total
n=176 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
60.7 years
STANDARD_DEVIATION 8.25 • n=5 Participants
|
60.2 years
STANDARD_DEVIATION 8.41 • n=7 Participants
|
61.1 years
STANDARD_DEVIATION 7.79 • n=5 Participants
|
60.8 years
STANDARD_DEVIATION 8.02 • n=4 Participants
|
|
Sex: Female, Male
Female
|
30 Participants
n=5 Participants
|
26 Participants
n=7 Participants
|
51 Participants
n=5 Participants
|
107 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
14 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
38 Participants
n=5 Participants
|
69 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Baseline, Week 8Population: Safety population consisted of all randomized participants who received the study treatment and were analyzed by treatment actually received.
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.
Outcome measures
| Measure |
OnabotulinumtoxinA 400 U
n=44 Participants
OnabotulinumtoxinA 400 U injection into the intra-articular space of the study knee on Day 1.
|
OnabotulinumtoxinA 200 U
n=43 Participants
OnabotulinumtoxinA 200 U injection into the intra-articular space of the study knee on Day 1.
|
Placebo
n=89 Participants
Placebo (Normal Saline) injection into the intra-articular space of the study knee on Day 1.
|
|---|---|---|---|
|
Change From Baseline in the 7-Day Average Daily Pain Score Using an 11-Point Scale
Baseline
|
5.92 score on a scale
Standard Deviation 1.222
|
6.09 score on a scale
Standard Deviation 1.313
|
6.00 score on a scale
Standard Deviation 1.150
|
|
Change From Baseline in the 7-Day Average Daily Pain Score Using an 11-Point Scale
Change from Baseline at Week 8
|
-1.68 score on a scale
Standard Deviation 1.641
|
-2.07 score on a scale
Standard Deviation 1.602
|
-1.98 score on a scale
Standard Deviation 1.793
|
SECONDARY outcome
Timeframe: Baseline, Weeks 1, 4, 8, 12, 16, 20 and 24Population: Safety population consisted of all randomized participants who received the study treatment and were analyzed by treatment actually received. "n" in the category is the number of participants with data available at the given time-point.
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.
Outcome measures
| Measure |
OnabotulinumtoxinA 400 U
n=44 Participants
OnabotulinumtoxinA 400 U injection into the intra-articular space of the study knee on Day 1.
|
OnabotulinumtoxinA 200 U
n=43 Participants
OnabotulinumtoxinA 200 U injection into the intra-articular space of the study knee on Day 1.
|
Placebo
n=89 Participants
Placebo (Normal Saline) injection into the intra-articular space of the study knee on Day 1.
|
|---|---|---|---|
|
Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC™) Pain Score Using an 11-Point Scale
Baseline
|
5.84 score on a scale
Standard Deviation 1.629
|
5.41 score on a scale
Standard Deviation 1.806
|
5.34 score on a scale
Standard Deviation 1.548
|
|
Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC™) Pain Score Using an 11-Point Scale
Change from Baseline at Week 1
|
-1.75 score on a scale
Standard Deviation 1.567
|
-1.61 score on a scale
Standard Deviation 1.666
|
-1.62 score on a scale
Standard Deviation 1.805
|
|
Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC™) Pain Score Using an 11-Point Scale
Change from Baseline at Week 4
|
-1.82 score on a scale
Standard Deviation 1.893
|
-1.67 score on a scale
Standard Deviation 1.763
|
-1.81 score on a scale
Standard Deviation 1.848
|
|
Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC™) Pain Score Using an 11-Point Scale
Change from Baseline at Week 8
|
-2.02 score on a scale
Standard Deviation 1.899
|
-1.52 score on a scale
Standard Deviation 1.907
|
-1.76 score on a scale
Standard Deviation 1.976
|
|
Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC™) Pain Score Using an 11-Point Scale
Change from Baseline at Week 12
|
-1.81 score on a scale
Standard Deviation 1.975
|
-1.82 score on a scale
Standard Deviation 1.870
|
-1.75 score on a scale
Standard Deviation 2.014
|
|
Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC™) Pain Score Using an 11-Point Scale
Change from Baseline at Week 16
|
-1.67 score on a scale
Standard Deviation 1.841
|
-1.64 score on a scale
Standard Deviation 2.174
|
-1.62 score on a scale
Standard Deviation 1.901
|
|
Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC™) Pain Score Using an 11-Point Scale
Change from Baseline at Week 20
|
-1.79 score on a scale
Standard Deviation 1.937
|
-1.68 score on a scale
Standard Deviation 2.066
|
-1.78 score on a scale
Standard Deviation 2.037
|
|
Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC™) Pain Score Using an 11-Point Scale
Change from Baseline at Week 24
|
-1.93 score on a scale
Standard Deviation 2.289
|
-1.81 score on a scale
Standard Deviation 2.181
|
-1.69 score on a scale
Standard Deviation 2.008
|
SECONDARY outcome
Timeframe: Baseline, Weeks 1, 4, 8, 12, 16, 20 and 24Population: Safety population consisted of all randomized participants who received the study treatment and were analyzed by treatment actually received. "n" in the category is the number of participants with data available at the given time-point.
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.
Outcome measures
| Measure |
OnabotulinumtoxinA 400 U
n=44 Participants
OnabotulinumtoxinA 400 U injection into the intra-articular space of the study knee on Day 1.
|
OnabotulinumtoxinA 200 U
n=43 Participants
OnabotulinumtoxinA 200 U injection into the intra-articular space of the study knee on Day 1.
|
Placebo
n=89 Participants
Placebo (Normal Saline) injection into the intra-articular space of the study knee on Day 1.
|
|---|---|---|---|
|
Change From Baseline in the WOMAC™ Physical Function Score Using an 11-Point Scale
Baseline
|
5.56 score on a scale
Standard Deviation 1.804
|
5.35 score on a scale
Standard Deviation 1.995
|
4.99 score on a scale
Standard Deviation 1.854
|
|
Change From Baseline in the WOMAC™ Physical Function Score Using an 11-Point Scale
Change from Baseline at Week 1
|
-1.33 score on a scale
Standard Deviation 1.424
|
-1.64 score on a scale
Standard Deviation 1.870
|
-1.44 score on a scale
Standard Deviation 1.933
|
|
Change From Baseline in the WOMAC™ Physical Function Score Using an 11-Point Scale
Change from Baseline at Week 4
|
-1.26 score on a scale
Standard Deviation 1.672
|
-1.66 score on a scale
Standard Deviation 1.908
|
-1.35 score on a scale
Standard Deviation 2.069
|
|
Change From Baseline in the WOMAC™ Physical Function Score Using an 11-Point Scale
Change from Baseline at Week 8
|
-1.54 score on a scale
Standard Deviation 1.819
|
-1.50 score on a scale
Standard Deviation 2.043
|
-1.27 score on a scale
Standard Deviation 2.070
|
|
Change From Baseline in the WOMAC™ Physical Function Score Using an 11-Point Scale
Change from Baseline at Week 12
|
-1.30 score on a scale
Standard Deviation 1.648
|
-1.68 score on a scale
Standard Deviation 1.781
|
-1.40 score on a scale
Standard Deviation 2.170
|
|
Change From Baseline in the WOMAC™ Physical Function Score Using an 11-Point Scale
Change from Baseline at Week 16
|
-1.29 score on a scale
Standard Deviation 1.558
|
-1.59 score on a scale
Standard Deviation 2.127
|
-1.09 score on a scale
Standard Deviation 1.991
|
|
Change From Baseline in the WOMAC™ Physical Function Score Using an 11-Point Scale
Change from Baseline at Week 20
|
-1.34 score on a scale
Standard Deviation 1.651
|
-1.44 score on a scale
Standard Deviation 2.172
|
-1.18 score on a scale
Standard Deviation 2.087
|
|
Change From Baseline in the WOMAC™ Physical Function Score Using an 11-Point Scale
Change from Baseline at Week 24
|
-1.48 score on a scale
Standard Deviation 2.029
|
-1.56 score on a scale
Standard Deviation 2.232
|
-1.12 score on a scale
Standard Deviation 1.998
|
SECONDARY outcome
Timeframe: Weeks 1, 4, 8, 12, 16, 20 and 24Population: Safety population consisted of all randomized participants who received the study treatment and were analyzed by treatment actually received. "n" in the category is the number of participants with data available at the given time-point.
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.
Outcome measures
| Measure |
OnabotulinumtoxinA 400 U
n=44 Participants
OnabotulinumtoxinA 400 U injection into the intra-articular space of the study knee on Day 1.
|
OnabotulinumtoxinA 200 U
n=43 Participants
OnabotulinumtoxinA 200 U injection into the intra-articular space of the study knee on Day 1.
|
Placebo
n=89 Participants
Placebo (Normal Saline) injection into the intra-articular space of the study knee on Day 1.
|
|---|---|---|---|
|
Patient Global Impression of Change (GIC) Using a 7-Point Scale
Week 1
|
0.9 score on a scale
Standard Deviation 1.00
|
1.2 score on a scale
Standard Deviation 0.97
|
1.1 score on a scale
Standard Deviation 1.09
|
|
Patient Global Impression of Change (GIC) Using a 7-Point Scale
Week 4
|
0.9 score on a scale
Standard Deviation 1.24
|
1.2 score on a scale
Standard Deviation 1.23
|
1.2 score on a scale
Standard Deviation 1.10
|
|
Patient Global Impression of Change (GIC) Using a 7-Point Scale
Week 8
|
1.1 score on a scale
Standard Deviation 1.09
|
0.9 score on a scale
Standard Deviation 1.35
|
1.0 score on a scale
Standard Deviation 1.00
|
|
Patient Global Impression of Change (GIC) Using a 7-Point Scale
Week 12
|
1.1 score on a scale
Standard Deviation 1.35
|
1.2 score on a scale
Standard Deviation 1.30
|
1.0 score on a scale
Standard Deviation 1.14
|
|
Patient Global Impression of Change (GIC) Using a 7-Point Scale
Week 16
|
1.1 score on a scale
Standard Deviation 1.31
|
1.1 score on a scale
Standard Deviation 1.36
|
1.0 score on a scale
Standard Deviation 1.10
|
|
Patient Global Impression of Change (GIC) Using a 7-Point Scale
Week 20
|
1.1 score on a scale
Standard Deviation 1.24
|
1.0 score on a scale
Standard Deviation 1.42
|
1.0 score on a scale
Standard Deviation 1.20
|
|
Patient Global Impression of Change (GIC) Using a 7-Point Scale
Week 24
|
0.8 score on a scale
Standard Deviation 1.34
|
1.0 score on a scale
Standard Deviation 1.41
|
0.9 score on a scale
Standard Deviation 1.28
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: Safety population consisted of all randomized participants who received the study treatment and were analyzed by treatment actually received.
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.
Outcome measures
| Measure |
OnabotulinumtoxinA 400 U
n=44 Participants
OnabotulinumtoxinA 400 U injection into the intra-articular space of the study knee on Day 1.
|
OnabotulinumtoxinA 200 U
n=43 Participants
OnabotulinumtoxinA 200 U injection into the intra-articular space of the study knee on Day 1.
|
Placebo
n=89 Participants
Placebo (Normal Saline) injection into the intra-articular space of the study knee on Day 1.
|
|---|---|---|---|
|
Change From Baseline in the 7-Day Average Daily Worst Pain Score Using an 11-Point Scale
Baseline
|
6.50 score on a scale
Standard Deviation 1.243
|
6.84 score on a scale
Standard Deviation 1.342
|
6.63 score on a scale
Standard Deviation 1.157
|
|
Change From Baseline in the 7-Day Average Daily Worst Pain Score Using an 11-Point Scale
Week 24
|
-1.48 score on a scale
Standard Deviation 1.894
|
-2.07 score on a scale
Standard Deviation 2.126
|
-1.80 score on a scale
Standard Deviation 1.896
|
Adverse Events
OnabotulinumtoxinA 400 U
Serious events: 6 serious events
Other events: 9 other events
Deaths: 0 deaths
OnabotulinumtoxinA 200 U
Serious events: 4 serious events
Other events: 15 other events
Deaths: 0 deaths
Placebo
Serious events: 6 serious events
Other events: 26 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
OnabotulinumtoxinA 400 U
n=44 participants at risk
OnabotulinumtoxinA 400 U injection into the intra-articular space of the study knee on Day 1.
|
OnabotulinumtoxinA 200 U
n=43 participants at risk
OnabotulinumtoxinA 200 U injection into the intra-articular space of the study knee on Day 1.
|
Placebo
n=89 participants at risk
Placebo (Normal Saline) injection into the intra-articular space of the study knee on Day 1.
|
|---|---|---|---|
|
Nervous system disorders
Basal ganglia infarction
|
0.00%
0/44 • Up to Day 172
|
2.3%
1/43 • Up to Day 172
|
0.00%
0/89 • Up to Day 172
|
|
Infections and infestations
Incision site infection
|
2.3%
1/44 • Up to Day 172
|
0.00%
0/43 • Up to Day 172
|
0.00%
0/89 • Up to Day 172
|
|
Infections and infestations
Pneumonia
|
2.3%
1/44 • Up to Day 172
|
0.00%
0/43 • Up to Day 172
|
0.00%
0/89 • Up to Day 172
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
2.3%
1/44 • Up to Day 172
|
0.00%
0/43 • Up to Day 172
|
0.00%
0/89 • Up to Day 172
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/44 • Up to Day 172
|
2.3%
1/43 • Up to Day 172
|
0.00%
0/89 • Up to Day 172
|
|
Eye disorders
Retinal detachment
|
2.3%
1/44 • Up to Day 172
|
0.00%
0/43 • Up to Day 172
|
0.00%
0/89 • Up to Day 172
|
|
Gastrointestinal disorders
Constipation
|
2.3%
1/44 • Up to Day 172
|
0.00%
0/43 • Up to Day 172
|
0.00%
0/89 • Up to Day 172
|
|
Gastrointestinal disorders
Nausea
|
2.3%
1/44 • Up to Day 172
|
0.00%
0/43 • Up to Day 172
|
0.00%
0/89 • Up to Day 172
|
|
Gastrointestinal disorders
Vomiting
|
2.3%
1/44 • Up to Day 172
|
0.00%
0/43 • Up to Day 172
|
0.00%
0/89 • Up to Day 172
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/44 • Up to Day 172
|
2.3%
1/43 • Up to Day 172
|
0.00%
0/89 • Up to Day 172
|
|
Nervous system disorders
Cerebrovascular accident
|
2.3%
1/44 • Up to Day 172
|
0.00%
0/43 • Up to Day 172
|
0.00%
0/89 • Up to Day 172
|
|
Nervous system disorders
Dizziness
|
2.3%
1/44 • Up to Day 172
|
0.00%
0/43 • Up to Day 172
|
0.00%
0/89 • Up to Day 172
|
|
Cardiac disorders
Bradycardia
|
0.00%
0/44 • Up to Day 172
|
0.00%
0/43 • Up to Day 172
|
1.1%
1/89 • Up to Day 172
|
|
Injury, poisoning and procedural complications
Muscle strain
|
0.00%
0/44 • Up to Day 172
|
2.3%
1/43 • Up to Day 172
|
0.00%
0/89 • Up to Day 172
|
|
Injury, poisoning and procedural complications
Meniscus injury
|
0.00%
0/44 • Up to Day 172
|
0.00%
0/43 • Up to Day 172
|
1.1%
1/89 • Up to Day 172
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.00%
0/44 • Up to Day 172
|
0.00%
0/43 • Up to Day 172
|
2.2%
2/89 • Up to Day 172
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.00%
0/44 • Up to Day 172
|
0.00%
0/43 • Up to Day 172
|
1.1%
1/89 • Up to Day 172
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/44 • Up to Day 172
|
0.00%
0/43 • Up to Day 172
|
1.1%
1/89 • Up to Day 172
|
Other adverse events
| Measure |
OnabotulinumtoxinA 400 U
n=44 participants at risk
OnabotulinumtoxinA 400 U injection into the intra-articular space of the study knee on Day 1.
|
OnabotulinumtoxinA 200 U
n=43 participants at risk
OnabotulinumtoxinA 200 U injection into the intra-articular space of the study knee on Day 1.
|
Placebo
n=89 participants at risk
Placebo (Normal Saline) injection into the intra-articular space of the study knee on Day 1.
|
|---|---|---|---|
|
Musculoskeletal and connective tissue disorders
Joint swelling
|
0.00%
0/44 • Up to Day 172
|
9.3%
4/43 • Up to Day 172
|
4.5%
4/89 • Up to Day 172
|
|
Vascular disorders
Hypertension
|
2.3%
1/44 • Up to Day 172
|
7.0%
3/43 • Up to Day 172
|
2.2%
2/89 • Up to Day 172
|
|
Infections and infestations
Nasopharyngitis
|
6.8%
3/44 • Up to Day 172
|
4.7%
2/43 • Up to Day 172
|
9.0%
8/89 • Up to Day 172
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
2.3%
1/44 • Up to Day 172
|
4.7%
2/43 • Up to Day 172
|
5.6%
5/89 • Up to Day 172
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
9.1%
4/44 • Up to Day 172
|
20.9%
9/43 • Up to Day 172
|
10.1%
9/89 • Up to Day 172
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee A disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 90 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.
- Publication restrictions are in place
Restriction type: OTHER