Trial Outcomes & Findings for Phase 2a Dose-Ranging Study to Evaluate Safety and Effectiveness of AA4500 in Treatment of Dupuytren's Disease Nodules (NCT NCT02193828)

NCT ID: NCT02193828

Last Updated: 2017-10-05

Results Overview

Percent change from baseline in surface area and volume of the treated nodule was determined from hand-held caliper measurements of the length and width of the nodule. Percent change = 100\*(Day 57 area \[or volume\] - baseline area \[or volume\])/baseline area \[or volume\]. A negative value represents the improvement from baseline (decreased size) while a positive value represents worsening.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 76 participants
• Primary outcome timeframe: Baseline, Day 57
• Results posted on: 2017-10-05

Participant Flow

Participant milestones

Measure	AA4500 0.60 mg Collagenase clostridium histolyticum (AA4500), single 0.60 mg injection into the nodule	AA4500 0.40 mg Collagenase clostridium histolyticum (AA4500), single 0.40 mg injection into the nodule	AA4500 0.25 mg Collagenase clostridium histolyticum (AA4500), single 0.25 mg injection into the nodule	Placebo Placebo, single 0.25 mg, 0.40 mg, or 0.60 mg injection into the nodule
Overall Study STARTED	18	18	23	17
Overall Study COMPLETED	18	18	22	16
Overall Study NOT COMPLETED	0	0	1	1

Reasons for withdrawal

Measure	AA4500 0.60 mg Collagenase clostridium histolyticum (AA4500), single 0.60 mg injection into the nodule	AA4500 0.40 mg Collagenase clostridium histolyticum (AA4500), single 0.40 mg injection into the nodule	AA4500 0.25 mg Collagenase clostridium histolyticum (AA4500), single 0.25 mg injection into the nodule	Placebo Placebo, single 0.25 mg, 0.40 mg, or 0.60 mg injection into the nodule
Overall Study Withdrawal by Subject	0	0	1	1

Baseline Characteristics

Phase 2a Dose-Ranging Study to Evaluate Safety and Effectiveness of AA4500 in Treatment of Dupuytren's Disease Nodules

Baseline characteristics by cohort

Measure	AA4500 0.60 mg n=18 Participants Collagenase clostridium histolyticum (AA4500), single 0.60 mg injection into the nodule	AA4500 0.40 mg n=18 Participants Collagenase clostridium histolyticum (AA4500), single 0.40 mg injection into the nodule	AA4500 0.25 mg n=22 Participants Collagenase clostridium histolyticum (AA4500), single 0.25 mg injection into the nodule	Placebo n=17 Participants Placebo, single 0.25 mg, 0.40 mg, or 0.60 mg injection into the nodule	Total n=75 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	13 Participants n=5 Participants	12 Participants n=7 Participants	16 Participants n=5 Participants	11 Participants n=4 Participants	52 Participants n=21 Participants
Age, Categorical >=65 years	5 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants	6 Participants n=4 Participants	23 Participants n=21 Participants
Age, Continuous	62.0 years n=5 Participants	60.0 years n=7 Participants	57.0 years n=5 Participants	58.0 years n=4 Participants	58.0 years n=21 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	10 Participants n=7 Participants	11 Participants n=5 Participants	7 Participants n=4 Participants	34 Participants n=21 Participants
Sex: Female, Male Male	12 Participants n=5 Participants	8 Participants n=7 Participants	11 Participants n=5 Participants	10 Participants n=4 Participants	41 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	4 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	17 Participants n=5 Participants	17 Participants n=7 Participants	21 Participants n=5 Participants	16 Participants n=4 Participants	71 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) White	18 Participants n=5 Participants	17 Participants n=7 Participants	22 Participants n=5 Participants	17 Participants n=4 Participants	74 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Region of Enrollment United States	12 participants n=5 Participants	10 participants n=7 Participants	14 participants n=5 Participants	12 participants n=4 Participants	48 participants n=21 Participants
Region of Enrollment Australia	6 participants n=5 Participants	8 participants n=7 Participants	8 participants n=5 Participants	5 participants n=4 Participants	27 participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline, Day 57

Population: Analysis based on Modified Intent-to-Treat (mITT) population; all randomized subjects who received study medication and had pre- and post-baseline nodule measurements for ultrasound and calipers. Analytical outliers (subjects whose percent change in ultrasound volume was greater than the 75th percentile + 3× the interquartile range) were excluded.

Percent change from baseline in surface area and volume of the treated nodule was determined from hand-held caliper measurements of the length and width of the nodule. Percent change = 100*(Day 57 area [or volume] - baseline area [or volume])/baseline area [or volume]. A negative value represents the improvement from baseline (decreased size) while a positive value represents worsening.

Outcome measures

Measure	AA4500 0.60 mg n=17 Participants Collagenase clostridium histolyticum (AA4500), single 0.60 mg injection into the nodule	AA4500 0.40 mg n=18 Participants Collagenase clostridium histolyticum (AA4500), single 0.40 mg injection into the nodule	AA4500 0.25 mg n=20 Participants Collagenase clostridium histolyticum (AA4500), single 0.25 mg injection into the nodule	Placebo n=15 Participants Placebo, single 0.25 mg, 0.40 mg, or 0.60 mg injection into the nodule
Percent Change From Baseline in Surface Area and Volume of the Treated Nodule at Day 57 Using Caliper Measurements Surface Area	-81.61 percentage of change Standard Deviation 20.251	-80.11 percentage of change Standard Deviation 21.459	-58.30 percentage of change Standard Deviation 29.849	-41.76 percentage of change Standard Deviation 32.445
Percent Change From Baseline in Surface Area and Volume of the Treated Nodule at Day 57 Using Caliper Measurements Volume	-89.03 percentage of change Standard Deviation 15.016	-87.58 percentage of change Standard Deviation 16.372	-68.15 percentage of change Standard Deviation 33.859	-49.13 percentage of change Standard Deviation 36.736

SECONDARY outcome

Timeframe: Baseline, Day 57

Population: Analysis based on mITT population; all randomized subjects who received study medication and had pre- and post-baseline nodule measurements for ultrasound and calipers. Analytical outliers (subjects whose percent change in ultrasound volume was greater than the 75th percentile + 3× the interquartile range) were excluded.

Percent change from baseline in surface area and volume of the treated nodule was determined from ultrasound measurements of the length, width, and depth of the nodule. Percent change = 100*(Day 57 area [or volume] - baseline area [or volume])/baseline area [or volume]. A negative value represents the improvement from baseline (decreased size) while a positive value represents worsening.

Outcome measures

Measure	AA4500 0.60 mg n=17 Participants Collagenase clostridium histolyticum (AA4500), single 0.60 mg injection into the nodule	AA4500 0.40 mg n=18 Participants Collagenase clostridium histolyticum (AA4500), single 0.40 mg injection into the nodule	AA4500 0.25 mg n=20 Participants Collagenase clostridium histolyticum (AA4500), single 0.25 mg injection into the nodule	Placebo n=15 Participants Placebo, single 0.25 mg, 0.40 mg, or 0.60 mg injection into the nodule
Percent Change From Baseline in Surface Area and Volume of the Treated Nodule at Day 57 Using Ultrasound Surface Area	-34.23 percentage of change Standard Deviation 41.353	-19.37 percentage of change Standard Deviation 39.658	-10.30 percentage of change Standard Deviation 41.696	-4.54 percentage of change Standard Deviation 54.784
Percent Change From Baseline in Surface Area and Volume of the Treated Nodule at Day 57 Using Ultrasound Volume	-40.99 percentage of change Standard Deviation 46.612	-13.01 percentage of change Standard Deviation 68.804	-9.52 percentage of change Standard Deviation 60.156	-7.19 percentage of change Standard Deviation 69.877

SECONDARY outcome

Timeframe: Baseline, Day 57

Population: Analysis based on mITT population; all randomized subjects who received an injection of study medication and had pre- and post-baseline nodule measurements for both ultrasound and calipers. Subjects with an incomplete assessment (not done) on Day 57 were excluded.

Investigators determined the consistency of the nodule through palpitation using a 5-point scale: 5 = hard (solid), 4 = firm throughout, 3 = moderate firmness, 2 = soft, and 1 = non-palpable. The change scores could range from +4 (greatest worsening in consistency) to -4 (greatest improvement in consistency); a negative change from baseline value reflects improvement from baseline (softening) while a positive value reflects worsening.

Outcome measures

Measure	AA4500 0.60 mg n=16 Participants Collagenase clostridium histolyticum (AA4500), single 0.60 mg injection into the nodule	AA4500 0.40 mg n=17 Participants Collagenase clostridium histolyticum (AA4500), single 0.40 mg injection into the nodule	AA4500 0.25 mg n=22 Participants Collagenase clostridium histolyticum (AA4500), single 0.25 mg injection into the nodule	Placebo n=15 Participants Placebo, single 0.25 mg, 0.40 mg, or 0.60 mg injection into the nodule
Change From Baseline in Consistency of the Treated Nodules at Day 57	-1.9 units on a scale Standard Deviation 0.93	-1.9 units on a scale Standard Deviation 1.05	-1.2 units on a scale Standard Deviation 1.10	-0.3 units on a scale Standard Deviation 0.96

SECONDARY outcome

Timeframe: Baseline, Day 57

Population: Analysis based on mITT population; all randomized subjects who received an injection of study medication and had pre- and post-baseline nodule measurements for both ultrasound and calipers. Subjects with an incomplete assessment (not done) on Day 57 were excluded.

A durometer was used to assess nodule hardness on a scale of 0 (soft) to 100 (hard). Percent change = 100*(Day 57 hardness - baseline hardness)/baseline hardness. A negative value represents the improvement from baseline (softening) while a positive value represents worsening.

Outcome measures

Measure	AA4500 0.60 mg n=16 Participants Collagenase clostridium histolyticum (AA4500), single 0.60 mg injection into the nodule	AA4500 0.40 mg n=17 Participants Collagenase clostridium histolyticum (AA4500), single 0.40 mg injection into the nodule	AA4500 0.25 mg n=22 Participants Collagenase clostridium histolyticum (AA4500), single 0.25 mg injection into the nodule	Placebo n=15 Participants Placebo, single 0.25 mg, 0.40 mg, or 0.60 mg injection into the nodule
Percent Change From Baseline in Hardness of the Treated Nodule at Day 57	-17.05 percentage of change Standard Deviation 15.584	-30.40 percentage of change Standard Deviation 24.930	-17.87 percentage of change Standard Deviation 22.265	4.80 percentage of change Standard Deviation 23.959

SECONDARY outcome

Timeframe: Baseline, Day 57

Population: Analysis based on mITT population; all randomized subjects who received an injection of study medication and had pre- and post-baseline nodule measurements for both ultrasound and calipers. Subjects with an incomplete assessment (not done) on Day 57 were excluded.

After the nodule was squeezed using a dynamometer, subjects were asked to rate the amount of pain they felt on an 11-point visual analog scale (VAS) from 0 (no pain or discomfort) to 10 (extreme pain or discomfort). A negative change from baseline value reflects improvement from baseline (less pain) while a positive value reflects worsening.

Outcome measures

Measure	AA4500 0.60 mg n=16 Participants Collagenase clostridium histolyticum (AA4500), single 0.60 mg injection into the nodule	AA4500 0.40 mg n=17 Participants Collagenase clostridium histolyticum (AA4500), single 0.40 mg injection into the nodule	AA4500 0.25 mg n=22 Participants Collagenase clostridium histolyticum (AA4500), single 0.25 mg injection into the nodule	Placebo n=15 Participants Placebo, single 0.25 mg, 0.40 mg, or 0.60 mg injection into the nodule
Change From Baseline in Nodular Pain of the Treated Nodule at Day 57	-0.8 units on a scale Standard Deviation 1.97	-1.6 units on a scale Standard Deviation 2.21	-1.7 units on a scale Standard Deviation 2.57	-0.5 units on a scale Standard Deviation 1.77

SECONDARY outcome

Timeframe: Day 57

Population: Analysis based on mITT population; all randomized subjects who received an injection of study medication and had pre- and post-baseline nodule measurements for both ultrasound and calipers.

Investigators were asked to determine the degree of improvement in the subject's treated nodule compared with screening on a 7-point scale: 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse.

Outcome measures

Measure	AA4500 0.60 mg n=18 Participants Collagenase clostridium histolyticum (AA4500), single 0.60 mg injection into the nodule	AA4500 0.40 mg n=18 Participants Collagenase clostridium histolyticum (AA4500), single 0.40 mg injection into the nodule	AA4500 0.25 mg n=22 Participants Collagenase clostridium histolyticum (AA4500), single 0.25 mg injection into the nodule	Placebo n=16 Participants Placebo, single 0.25 mg, 0.40 mg, or 0.60 mg injection into the nodule
Investigator Global Assessment of Improvement With Treatment	1.7 units on a scale Standard Deviation 0.84	1.7 units on a scale Standard Deviation 0.75	2.5 units on a scale Standard Deviation 1.10	3.0 units on a scale Standard Deviation 1.15

SECONDARY outcome

Timeframe: Day 57

Population: Analysis based on mITT population; all randomized subjects who received an injection of study medication and had pre- and post-baseline nodule measurements for both ultrasound and calipers.

Subjects were asked to rate their satisfaction with treatment on a 5-point scale: 1 = very satisfied, 2 = quite satisfied, 3 = neither satisfied nor dissatisfied, 4 = quite dissatisfied, and 5 = very dissatisfied.

Outcome measures

Measure	AA4500 0.60 mg n=18 Participants Collagenase clostridium histolyticum (AA4500), single 0.60 mg injection into the nodule	AA4500 0.40 mg n=18 Participants Collagenase clostridium histolyticum (AA4500), single 0.40 mg injection into the nodule	AA4500 0.25 mg n=22 Participants Collagenase clostridium histolyticum (AA4500), single 0.25 mg injection into the nodule	Placebo n=16 Participants Placebo, single 0.25 mg, 0.40 mg, or 0.60 mg injection into the nodule
Subject Satisfaction With Treatment	1.5 units on a scale Standard Deviation 0.79	1.6 units on a scale Standard Deviation 0.85	2.3 units on a scale Standard Deviation 1.17	2.8 units on a scale Standard Deviation 1.34

SECONDARY outcome

Timeframe: Day 57

Population: Analysis based on mITT population; all randomized subjects who received an injection of study medication and had pre- and post-baseline nodule measurements for both ultrasound and calipers.

A composite responder is a subject who had an improved assessment [values of 1 (very much improved), 2 (much improved), or 3 (minimally improved)] on the investigator global assessment and had a satisfied assessment [values of 1 (very satisfied) or 2 (quite satisfied)] on the subject assessment.

Outcome measures

Measure	AA4500 0.60 mg n=18 Participants Collagenase clostridium histolyticum (AA4500), single 0.60 mg injection into the nodule	AA4500 0.40 mg n=18 Participants Collagenase clostridium histolyticum (AA4500), single 0.40 mg injection into the nodule	AA4500 0.25 mg n=22 Participants Collagenase clostridium histolyticum (AA4500), single 0.25 mg injection into the nodule	Placebo n=16 Participants Placebo, single 0.25 mg, 0.40 mg, or 0.60 mg injection into the nodule
Composite Responder Analysis Responder: Yes	14 participants	16 participants	12 participants	6 participants
Composite Responder Analysis Responder: No	4 participants	2 participants	10 participants	10 participants

Adverse Events

AA4500 0.60 mg

Serious events: 0 serious events

Other events: 17 other events

Deaths: 0 deaths

AA4500 0.40 mg

Serious events: 0 serious events

Other events: 18 other events

Deaths: 0 deaths

AA4500 0.25 mg

Serious events: 0 serious events

Other events: 21 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	AA4500 0.60 mg n=18 participants at risk Collagenase clostridium histolyticum (AA4500), single 0.60 mg injection into the nodule	AA4500 0.40 mg n=18 participants at risk Collagenase clostridium histolyticum (AA4500), single 0.40 mg injection into the nodule	AA4500 0.25 mg n=22 participants at risk Collagenase clostridium histolyticum (AA4500), single 0.25 mg injection into the nodule	Placebo n=17 participants at risk Placebo, single 0.25 mg, 0.40 mg, or 0.60 mg injection into the nodule
Blood and lymphatic system disorders Lymphadenopathy	5.6% 1/18 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	0.00% 0/18 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	0.00% 0/22 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	0.00% 0/17 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.
Gastrointestinal disorders Nausea	0.00% 0/18 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	5.6% 1/18 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	0.00% 0/22 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	0.00% 0/17 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.
General disorders Axillary pain	22.2% 4/18 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	5.6% 1/18 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	27.3% 6/22 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	0.00% 0/17 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.
General disorders Injection site bruising	33.3% 6/18 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	22.2% 4/18 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	22.7% 5/22 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	0.00% 0/17 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.
General disorders Injection site haemorrhage	5.6% 1/18 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	0.00% 0/18 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	9.1% 2/22 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	0.00% 0/17 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.
General disorders Injection site hypoaesthesia	5.6% 1/18 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	0.00% 0/18 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	0.00% 0/22 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	0.00% 0/17 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.
General disorders Injection site oedema	11.1% 2/18 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	0.00% 0/18 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	9.1% 2/22 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	0.00% 0/17 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.
General disorders Injection site pain	11.1% 2/18 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	22.2% 4/18 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	18.2% 4/22 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	0.00% 0/17 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.
General disorders Injection site pruritus	11.1% 2/18 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	16.7% 3/18 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	9.1% 2/22 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	5.9% 1/17 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.
General disorders Injection site swelling	0.00% 0/18 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	22.2% 4/18 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	22.7% 5/22 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	0.00% 0/17 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.
General disorders Local swelling	55.6% 10/18 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	38.9% 7/18 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	36.4% 8/22 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	17.6% 3/17 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.
General disorders Localised oedema	5.6% 1/18 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	5.6% 1/18 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	0.00% 0/22 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	0.00% 0/17 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.
General disorders Pain	0.00% 0/18 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	0.00% 0/18 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	0.00% 0/22 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	5.9% 1/17 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.
General disorders Tenderness	5.6% 1/18 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	0.00% 0/18 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	4.5% 1/22 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	0.00% 0/17 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.
Injury, poisoning and procedural complications Contusion	50.0% 9/18 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	50.0% 9/18 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	59.1% 13/22 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	5.9% 1/17 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.
Injury, poisoning and procedural complications Injection related reaction	5.6% 1/18 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	0.00% 0/18 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	4.5% 1/22 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	0.00% 0/17 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.
Investigations Liver function test abnormal	5.6% 1/18 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	0.00% 0/18 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	0.00% 0/22 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	0.00% 0/17 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/18 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	0.00% 0/18 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	0.00% 0/22 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	5.9% 1/17 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.
Musculoskeletal and connective tissue disorders Arthritis	0.00% 0/18 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	0.00% 0/18 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	0.00% 0/22 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	5.9% 1/17 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.
Musculoskeletal and connective tissue disorders Dupuytren's contracture	5.6% 1/18 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	0.00% 0/18 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	0.00% 0/22 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	0.00% 0/17 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.
Musculoskeletal and connective tissue disorders Joint range of motion decreased	0.00% 0/18 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	5.6% 1/18 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	0.00% 0/22 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	0.00% 0/17 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/18 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	0.00% 0/18 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	0.00% 0/22 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	5.9% 1/17 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.
Musculoskeletal and connective tissue disorders Pain in extremity	38.9% 7/18 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	55.6% 10/18 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	45.5% 10/22 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	5.9% 1/17 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.
Musculoskeletal and connective tissue disorders Pain in jaw	5.6% 1/18 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	0.00% 0/18 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	0.00% 0/22 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	0.00% 0/17 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.
Nervous system disorders Headache	0.00% 0/18 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	0.00% 0/18 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	0.00% 0/22 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	5.9% 1/17 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.
Skin and subcutaneous tissue disorders Blister	0.00% 0/18 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	5.6% 1/18 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	0.00% 0/22 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	0.00% 0/17 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.
Skin and subcutaneous tissue disorders Blood blister	5.6% 1/18 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	5.6% 1/18 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	0.00% 0/22 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	0.00% 0/17 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.
Skin and subcutaneous tissue disorders Night sweats	5.6% 1/18 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	0.00% 0/18 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	0.00% 0/22 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	0.00% 0/17 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.
Skin and subcutaneous tissue disorders Pruritus	5.6% 1/18 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	11.1% 2/18 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	9.1% 2/22 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	0.00% 0/17 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.
Skin and subcutaneous tissue disorders Rash	0.00% 0/18 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	5.6% 1/18 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	0.00% 0/22 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.	0.00% 0/17 • Adverse events were collected from enrollment through the end of the study (Day 57). Adverse events are reported for the Safety population; all randomized subjects who received an injection of study medication.

Additional Information

Clinical Trial Coordinator

Endo Pharmaceuticals, Inc.

Email: clinicalsite.inquiries@endo.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: OTHER