Trial Outcomes & Findings for Safety and Efficacy Study of Botulinum Toxin Type A as Treatment for Osteoarthritis Knee Pain (NCT NCT01518257)

NCT ID: NCT01518257

Last Updated: 2014-08-07

Results Overview

The patient rated their daily worst pain intensity in the study knee using an 11-point scale where: 0=no pain to 10=worst pain possible. The daily scores over the previous 14-day period were averaged. A negative change from Baseline indicated improvement.

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 121 participants
• Primary outcome timeframe: Baseline, Week 4
• Results posted on: 2014-08-07

Participant Flow

Participant milestones

Measure	Botulinum Toxin Type A A single 200U (2 mL) dose of botulinum toxin Type A injected into the intra-articular space of the study knee on Day 1.	Placebo A single 2 mL dose of Normal Saline (placebo) injected into the intra-articular space of the study knee on Day 1.
Overall Study STARTED	61	60
Overall Study COMPLETED	59	60
Overall Study NOT COMPLETED	2	0

Reasons for withdrawal

Measure	Botulinum Toxin Type A A single 200U (2 mL) dose of botulinum toxin Type A injected into the intra-articular space of the study knee on Day 1.	Placebo A single 2 mL dose of Normal Saline (placebo) injected into the intra-articular space of the study knee on Day 1.
Overall Study Lost to Follow-up	1	0
Overall Study Other Miscellaneous Reason	1	0

Baseline Characteristics

Safety and Efficacy Study of Botulinum Toxin Type A as Treatment for Osteoarthritis Knee Pain

Baseline characteristics by cohort

Measure	Botulinum Toxin Type A n=61 Participants A single 200U (2 mL) dose of botulinum toxin Type A injected into the intra-articular space of the study knee on Day 1.	Placebo n=60 Participants A single 2 mL dose of Normal Saline (placebo) injected into the intra-articular space of the study knee on Day 1.	Total n=121 Participants Total of all reporting groups
Age, Customized 40 to 64 Years	30 Participants n=5 Participants	31 Participants n=7 Participants	61 Participants n=5 Participants
Age, Customized ≥ 65 Years	31 Participants n=5 Participants	29 Participants n=7 Participants	60 Participants n=5 Participants
Sex: Female, Male Female	32 Participants n=5 Participants	30 Participants n=7 Participants	62 Participants n=5 Participants
Sex: Female, Male Male	29 Participants n=5 Participants	30 Participants n=7 Participants	59 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 4

Population: Safety population included all treated participants based on the actual treatment received.

The patient rated their daily worst pain intensity in the study knee using an 11-point scale where: 0=no pain to 10=worst pain possible. The daily scores over the previous 14-day period were averaged. A negative change from Baseline indicated improvement.

Outcome measures

Measure	Placebo n=60 Participants A single 2 mL dose of Normal Saline (placebo) injected into the intra-articular space of the study knee on Day 1.	Botulinum Toxin Type A n=61 Participants A single 200U (2 mL) dose of botulinum toxin Type A injected into the intra-articular space of the study knee on Day 1.
Change From Baseline in the Average Daily Worst Pain Intensity Score at Week 4 Baseline	6.5 Score on a scale Standard Deviation 1.28	6.4 Score on a scale Standard Deviation 1.09
Change From Baseline in the Average Daily Worst Pain Intensity Score at Week 4 Change from Baseline at Week 4	-1.8 Score on a scale Standard Deviation 1.87	-1.8 Score on a scale Standard Deviation 1.66

PRIMARY outcome

Timeframe: Baseline, Week 8

Population: Safety population included all treated participants based on the actual treatment received.

The patient rated their daily worst pain intensity in the study knee using an 11-point scale where: 0=no pain to 10=worst pain possible. The daily scores over the previous 14-day period were averaged. A negative change from Baseline indicated improvement.

Outcome measures

Measure	Placebo n=60 Participants A single 2 mL dose of Normal Saline (placebo) injected into the intra-articular space of the study knee on Day 1.	Botulinum Toxin Type A n=61 Participants A single 200U (2 mL) dose of botulinum toxin Type A injected into the intra-articular space of the study knee on Day 1.
Change From Baseline in the Average Daily Worst Pain Intensity Score at Week 8 Baseline	6.5 Score on a scale Standard Deviation 1.28	6.4 Score on a scale Standard Deviation 1.09
Change From Baseline in the Average Daily Worst Pain Intensity Score at Week 8 Change from Baseline at Week 8	-2.3 Score on a scale Standard Deviation 2.15	-2.2 Score on a scale Standard Deviation 1.96

PRIMARY outcome

Timeframe: Baseline, Week 12

Population: Safety population included all treated participants based on the actual treatment received.

The patient rated their daily worst pain intensity in the study knee using an 11-point scale where: 0=no pain to 10=worst pain possible. The daily scores over the previous 14-day period were averaged. A negative change from Baseline indicated improvement.

Outcome measures

Measure	Placebo n=60 Participants A single 2 mL dose of Normal Saline (placebo) injected into the intra-articular space of the study knee on Day 1.	Botulinum Toxin Type A n=61 Participants A single 200U (2 mL) dose of botulinum toxin Type A injected into the intra-articular space of the study knee on Day 1.
Change From Baseline in the Average Daily Worst Pain Intensity Score at Week 12 Baseline	6.5 Score on a scale Standard Deviation 1.28	6.4 Score on a scale Standard Deviation 1.09
Change From Baseline in the Average Daily Worst Pain Intensity Score at Week 12 Change from Baseline at Week 12	-2.5 Score on a scale Standard Deviation 2.24	-2.2 Score on a scale Standard Deviation 1.97

SECONDARY outcome

Timeframe: Baseline, Week 8

Population: Safety population included all treated participants based on the actual treatment received.

The WOMAC Total Index Score consisted of 24 components rated on a scale of 0 to 10. The Total Index Score included the WOMAC Pain Score (5 questions about pain where: 0=no pain to 10=extreme pain), the WOMAC Physical Function score (17 questions about the difficulty of daily activities where: 0=no difficulty to 10=extreme difficulty) and the WOMAC Stiffness Score (2 questions about stiffness where: 0=no stiffness to 10=extreme stiffness) for a total possible Index Score of 0 (best) to 240 (worst). A negative change from Baseline indicated improvement.

Outcome measures

Measure	Placebo n=60 Participants A single 2 mL dose of Normal Saline (placebo) injected into the intra-articular space of the study knee on Day 1.	Botulinum Toxin Type A n=61 Participants A single 200U (2 mL) dose of botulinum toxin Type A injected into the intra-articular space of the study knee on Day 1.
Change From Baseline in Western Ontario and McMaster Universities Arthritis (WOMAC™) Total Index Score Baseline	107.6 Score on a scale Standard Deviation 37.44	104.5 Score on a scale Standard Deviation 36.53
Change From Baseline in Western Ontario and McMaster Universities Arthritis (WOMAC™) Total Index Score Change from Baseline at Week 8 (n=59,59)	-43.8 Score on a scale Standard Deviation 47.25	-46.5 Score on a scale Standard Deviation 35.21

SECONDARY outcome

Timeframe: Baseline, Week 8

Population: Safety population included all treated participants based on the actual treatment received.

The WOMAC Pain Score included 5 questions about pain where: 0=no pain to 10=extreme pain for a total possible score of 0 (best) to 50 (worst). A negative change from Baseline indicated improvement.

Outcome measures

Measure	Placebo n=60 Participants A single 2 mL dose of Normal Saline (placebo) injected into the intra-articular space of the study knee on Day 1.	Botulinum Toxin Type A n=61 Participants A single 200U (2 mL) dose of botulinum toxin Type A injected into the intra-articular space of the study knee on Day 1.
Change From Baseline in WOMAC Pain Score Baseline	24.3 Score on a scale Standard Deviation 7.01	23.9 Score on a scale Standard Deviation 6.76
Change From Baseline in WOMAC Pain Score Change from Baseline at Week 8 (n=59,59)	-11.0 Score on a scale Standard Deviation 9.75	-10.7 Score on a scale Standard Deviation 7.27

SECONDARY outcome

Timeframe: Baseline, Week 8

Population: Safety population included all treated participants based on the actual treatment received.

The WOMAC Physical Function Score included 17 questions about the difficulty of daily activities where: 0=no difficulty to 10=extreme difficulty for a total possible score of 0 (best) to 170 (worst). A negative change from Baseline indicated improvement.

Outcome measures

Measure	Placebo n=60 Participants A single 2 mL dose of Normal Saline (placebo) injected into the intra-articular space of the study knee on Day 1.	Botulinum Toxin Type A n=61 Participants A single 200U (2 mL) dose of botulinum toxin Type A injected into the intra-articular space of the study knee on Day 1.
Change From Baseline in WOMAC Physical Function Score Baseline	73.3 Score on a scale Standard Deviation 29.77	71.0 Score on a scale Standard Deviation 28.43
Change From Baseline in WOMAC Physical Function Score Change from Baseline at Week 8 (n=59,59 )	-28.6 Score on a scale Standard Deviation 35.26	-31.7 Score on a scale Standard Deviation 26.41

SECONDARY outcome

Timeframe: Week 8

Population: Participants from the Safety population (all treated participants based on the actual treatment received) with data available for this outcome measure.

The participants 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 indicated worsening and positive scores indicated improvement.

Outcome measures

Measure	Placebo n=59 Participants A single 2 mL dose of Normal Saline (placebo) injected into the intra-articular space of the study knee on Day 1.	Botulinum Toxin Type A n=59 Participants A single 200U (2 mL) dose of botulinum toxin Type A injected into the intra-articular space of the study knee on Day 1.
Patient Global Impression of Change Score	1.0 Score on a scale Standard Deviation 1.38	1.3 Score on a scale Standard Deviation 1.28

POST_HOC outcome

Timeframe: Baseline, Weeks 4, 8 and 12

Population: Participants from the Safety population (all treated participants based on the actual treatment received) in a subgroup of patients with nociceptive pain (pain that is caused by nerves that react to injury or damage) at Baseline.

The patient rated their daily worst pain intensity in the study knee using an 11-point scale where: 0=no pain to 10=worst pain possible. The daily scores over the previous 14-day period were averaged. A negative change from Baseline indicated improvement.

Outcome measures

Measure	Placebo n=32 Participants A single 2 mL dose of Normal Saline (placebo) injected into the intra-articular space of the study knee on Day 1.	Botulinum Toxin Type A n=36 Participants A single 200U (2 mL) dose of botulinum toxin Type A injected into the intra-articular space of the study knee on Day 1.
Change From Baseline in the Average Daily Worst Pain Intensity Score in the Nociceptive Pain Group Baseline	6.4 Score on a scale Standard Deviation 1.35	6.4 Score on a scale Standard Deviation 1.01
Change From Baseline in the Average Daily Worst Pain Intensity Score in the Nociceptive Pain Group Change from Baseline at Week 4	-1.5 Score on a scale Standard Deviation 1.58	-1.9 Score on a scale Standard Deviation 1.56
Change From Baseline in the Average Daily Worst Pain Intensity Score in the Nociceptive Pain Group Change from Baseline at Week 8	-1.8 Score on a scale Standard Deviation 2.01	-2.6 Score on a scale Standard Deviation 2.01
Change From Baseline in the Average Daily Worst Pain Intensity Score in the Nociceptive Pain Group Change from Baseline at Week 12	-2.0 Score on a scale Standard Deviation 2.27	-2.6 Score on a scale Standard Deviation 1.79

POST_HOC outcome

Timeframe: Baseline, Week 8

Population: Participants from the Safety population (all treated participants based on the actual treatment received) in a subgroup of patients with nociceptive pain (pain that is caused by nerves that react to injury or damage) at Baseline.

The WOMAC Pain Score included 5 questions about pain where: 0=no pain to 10=extreme pain for a total possible score of 0 (best) to 50 (worst). A negative change from Baseline indicated improvement.

Outcome measures

Measure	Placebo n=32 Participants A single 2 mL dose of Normal Saline (placebo) injected into the intra-articular space of the study knee on Day 1.	Botulinum Toxin Type A n=36 Participants A single 200U (2 mL) dose of botulinum toxin Type A injected into the intra-articular space of the study knee on Day 1.
Change From Baseline in WOMAC Pain Score in the Nociceptive Pain Group Baseline	22.9 Score on a scale Standard Deviation 6.98	22.7 Score on a scale Standard Deviation 5.95
Change From Baseline in WOMAC Pain Score in the Nociceptive Pain Group Change from Baseline at Week 8 (n=35,31)	-7.5 Score on a scale Standard Deviation 9.00	-11.0 Score on a scale Standard Deviation 7.09

Adverse Events

Botulinum Toxin Type A

Serious events: 1 serious events

Other events: 7 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Measure	Botulinum Toxin Type A n=61 participants at risk A single 200U (2 mL) dose of botulinum toxin Type A injected into the intra-articular space of the study knee on Day 1.	Placebo n=60 participants at risk A single 2 mL dose of Normal Saline (placebo) injected into the intra-articular space of the study knee on Day 1.
Nervous system disorders Cerebrovascular accident	1.6% 1/61	0.00% 0/60

Other adverse events

Measure	Botulinum Toxin Type A n=61 participants at risk A single 200U (2 mL) dose of botulinum toxin Type A injected into the intra-articular space of the study knee on Day 1.	Placebo n=60 participants at risk A single 2 mL dose of Normal Saline (placebo) injected into the intra-articular space of the study knee on Day 1.
Infections and infestations Nasopharyngitis	1.6% 1/61	8.3% 5/60
Musculoskeletal and connective tissue disorders Osteoarthritis	4.9% 3/61	8.3% 5/60
Musculoskeletal and connective tissue disorders Arthralgia	4.9% 3/61	6.7% 4/60

Additional Information

Therapeutic Area Head,

Allergan, Inc

Phone: 714-246-4500

Email: clinicaltrials@allergan.com

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 30 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