Trial Outcomes & Findings for Non-US Study of AA4500 (XIAFLEX™, Proposed Name) in the Treatment of Advanced Dupuytren's Disease (NCT NCT00533273)

NCT ID: NCT00533273

Last Updated: 2017-12-02

Results Overview

Successfully treated or clinical success in primary joint defined as reduction in contracture to within 0-5° of normal within 30 days of injection.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 66 participants
• Primary outcome timeframe: Within 30 days after last injection
• Results posted on: 2017-12-02

Participant Flow

Participant milestones

Measure	AA4500 0.58 mg Collagenase clostridium histolyticum 0.58 mg injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints	Placebo Placebo (Sucrose and Tris) injection
Double-blind STARTED	45	21
Double-blind COMPLETED	45	19
Double-blind NOT COMPLETED	0	2
Open-label STARTED	64	0
Open-label COMPLETED	58	0
Open-label NOT COMPLETED	6	0

Reasons for withdrawal

Measure	AA4500 0.58 mg Collagenase clostridium histolyticum 0.58 mg injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints	Placebo Placebo (Sucrose and Tris) injection
Double-blind Withdrew consent	0	2
Open-label Withdrawal by Subject	6	0

Baseline Characteristics

Non-US Study of AA4500 (XIAFLEX™, Proposed Name) in the Treatment of Advanced Dupuytren's Disease

Baseline characteristics by cohort

Measure	AA4500 0.58 mg n=45 Participants Collagenase clostridium histolyticum 0.58 mg injected into MP and/or PIP joints	Placebo n=21 Participants Placebo (Sucrose and Tris) injection	Total n=66 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
Age, Categorical Between 18 and 65 years	25 Participants n=5 Participants	9 Participants n=7 Participants	34 Participants n=5 Participants
Age, Categorical >=65 years	20 Participants n=5 Participants	12 Participants n=7 Participants	32 Participants n=5 Participants
Age, Continuous	63.0 years STANDARD_DEVIATION 7.8 • n=5 Participants	65.5 years STANDARD_DEVIATION 11.1 • n=7 Participants	63.8 years STANDARD_DEVIATION 9.0 • n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	4 Participants n=7 Participants	10 Participants n=5 Participants
Sex: Female, Male Male	39 Participants n=5 Participants	17 Participants n=7 Participants	56 Participants n=5 Participants
Race/Ethnicity, Customized White	45 participants n=5 Participants	21 participants n=7 Participants	66 participants n=5 Participants
Region of Enrollment Australia	45 participants n=5 Participants	21 participants n=7 Participants	66 participants n=5 Participants

PRIMARY outcome

Timeframe: Within 30 days after last injection

Population: Subjects who were randomized and received at least 1 injection

Successfully treated or clinical success in primary joint defined as reduction in contracture to within 0-5° of normal within 30 days of injection.

Outcome measures

Measure	AA4500 0.58 mg n=45 Joints Collagenase clostridium histolyticum 0.58 mg injected into MP and/or PIP joints	Placebo n=21 Joints Placebo (Sucrose and Tris) injection
Reduction in Primary Joint Contracture to 5° or Less	44.4 Percentage of Joints	4.8 Percentage of Joints

SECONDARY outcome

Timeframe: Baseline, Within 30 days after last injection

Population: Subjects who were randomized and received at least 1 injection

Clinical improvement in primary joint defined as ≥50% reduction from baseline in the degree of contracture within 30 days after injection

Outcome measures

Measure	AA4500 0.58 mg n=45 Joints Collagenase clostridium histolyticum 0.58 mg injected into MP and/or PIP joints	Placebo n=21 Joints Placebo (Sucrose and Tris) injection
Clinical Improvement in Primary Joint After the Last Injection	77.8 Percentage of Joints	14.3 Percentage of Joints

SECONDARY outcome

Timeframe: Baseline, Day 30 after last injection

Population: Subjects who were randomized and received at least 1 injection

Percent change in degree of contracture of primary joint measured as 100 * (baseline contracture - last available post-injection contracture)/baseline contracture

Outcome measures

Measure	AA4500 0.58 mg n=45 Joints Collagenase clostridium histolyticum 0.58 mg injected into MP and/or PIP joints	Placebo n=21 Joints Placebo (Sucrose and Tris) injection
Percent Reduction From Baseline Contracture of Primary Joint After the Last Injection	70.5 Percentage of change Standard Deviation 29.21	13.6 Percentage of change Standard Deviation 26.10

SECONDARY outcome

Timeframe: Baseline, Day 30 after last injection

Population: Subjects who were randomized and received at least 1 injection

Change in degree of range of motion in primary joint measured as last available post-injection range of motion - baseline range of motion

Outcome measures

Measure	AA4500 0.58 mg n=45 Joints Collagenase clostridium histolyticum 0.58 mg injected into MP and/or PIP joints	Placebo n=21 Joints Placebo (Sucrose and Tris) injection
Change From Baseline Range of Motion in Primary Joint After the Last Injection	35.4 Degrees Standard Deviation 17.77	7.6 Degrees Standard Deviation 14.88

SECONDARY outcome

Timeframe: Within 30 days after last injection

Population: Subjects who were randomized and received at least 1 injection

Clinical success in primary joint defined as reduction in contracture to within 0-5° of normal within 30 days of injection, displayed in post injection time point categories

Outcome measures

Measure	AA4500 0.58 mg n=45 Joints Collagenase clostridium histolyticum 0.58 mg injected into MP and/or PIP joints	Placebo n=21 Joints Placebo (Sucrose and Tris) injection
Time to Reach Clinical Success in Primary Joint Injection 1, Day 1	2.2 Percentage of Joints	0.0 Percentage of Joints
Time to Reach Clinical Success in Primary Joint Injection 1, Day 7	6.7 Percentage of Joints	4.8 Percentage of Joints
Time to Reach Clinical Success in Primary Joint Injection 1, Day 30	17.8 Percentage of Joints	0.0 Percentage of Joints
Time to Reach Clinical Success in Primary Joint Injection 2, Day 1	0.0 Percentage of Joints	0.0 Percentage of Joints
Time to Reach Clinical Success in Primary Joint Injection 2, Day 7	4.4 Percentage of Joints	0.0 Percentage of Joints
Time to Reach Clinical Success in Primary Joint Injection 2, Day 30	8.9 Percentage of Joints	0.0 Percentage of Joints
Time to Reach Clinical Success in Primary Joint Injection 3, Day 1	4.4 Percentage of Joints	0.0 Percentage of Joints
Time to Reach Clinical Success in Primary Joint Injection 3, Day 7	0.0 Percentage of Joints	0.0 Percentage of Joints
Time to Reach Clinical Success in Primary Joint Injection 3, Day 30	0.0 Percentage of Joints	0.0 Percentage of Joints
Time to Reach Clinical Success in Primary Joint Did not reach Clinical Success	55.6 Percentage of Joints	95.2 Percentage of Joints

SECONDARY outcome

Timeframe: Within 30 days after first injection

Population: Subjects who were randomized and received at least 1 injection

Clinical success in primary joint defined as reduction in contracture to within 0-5° of normal within 30 days of injection.

Outcome measures

Measure	AA4500 0.58 mg n=45 Joints Collagenase clostridium histolyticum 0.58 mg injected into MP and/or PIP joints	Placebo n=21 Joints Placebo (Sucrose and Tris) injection
Clinical Success in Primary Joint After the First Injection	26.7 Percentage of Joints	4.8 Percentage of Joints

SECONDARY outcome

Timeframe: Baseline, Within 30 days after first injection

Population: Subjects who were randomized and received at least 1 injection

Clinical improvement in primary joint defined as ≥50% reduction from baseline in the degree of contracture within 30 days after injection

Outcome measures

Measure	AA4500 0.58 mg n=45 Joints Collagenase clostridium histolyticum 0.58 mg injected into MP and/or PIP joints	Placebo n=21 Joints Placebo (Sucrose and Tris) injection
Clinical Improvement in Primary Joint After the First Injection	60.0 Percentage of Joints	4.8 Percentage of Joints

SECONDARY outcome

Timeframe: Baseline, Day 30 after first injection

Population: Subjects who were randomized and received at least 1 injection

Percent change in degree of contracture of primary joint measured as 100 * (baseline contracture - last available post-injection contracture prior to next injection)/baseline contracture

Outcome measures

Measure	AA4500 0.58 mg n=45 Joints Collagenase clostridium histolyticum 0.58 mg injected into MP and/or PIP joints	Placebo n=21 Joints Placebo (Sucrose and Tris) injection
Percent Reduction From Baseline Contracture of Primary Joint After the First Injection	58.5 Percentage of change Standard Deviation 31.74	6.0 Percentage of change Standard Deviation 20.79

SECONDARY outcome

Timeframe: Baseline, Day 30 after first injection

Population: Subjects who were randomized and received at least 1 injection

Change in degree of range of motion in primary joint measured as last available post-injection range of motion prior to the next injection - baseline range of motion

Outcome measures

Measure	AA4500 0.58 mg n=45 Joints Collagenase clostridium histolyticum 0.58 mg injected into MP and/or PIP joints	Placebo n=21 Joints Placebo (Sucrose and Tris) injection
Change From Baseline Range of Motion in Primary Joint After the First Injection	28.6 Degrees Standard Deviation 17.41	3.6 Degrees Standard Deviation 9.51

SECONDARY outcome

Timeframe: Within 30 days after last injection

Population: Includes evaluable non-primary joints treated with AA4500 with baseline fixed flexion contracture \>5° and at least 1 post-injection contracture measurement in subjects who received at least 1 non-primary joint injection in either study period

Successfully treated or clinical success in non-primary joint defined as reduction in contracture to within 0-5° of normal within 30 days of injection.

Outcome measures

Measure	AA4500 0.58 mg n=89 Joints Collagenase clostridium histolyticum 0.58 mg injected into MP and/or PIP joints	Placebo Placebo (Sucrose and Tris) injection
Reduction in Non-primary Joint Contracture to 5° or Less After the Last Injection	53.9 Percentage of Joints	—

SECONDARY outcome

Timeframe: Baseline, Within 30 days after last injection

Population: Includes evaluable non-primary joints treated with AA4500 with baseline fixed flexion contracture \>5° and at least 1 post-injection contracture measurement in subjects who received at least 1 non-primary joint injection in either study period

Clinical improvement in non-primary joint defined as ≥50% reduction from baseline in the degree of contracture within 30 days after injection

Outcome measures

Measure	AA4500 0.58 mg n=89 Joints Collagenase clostridium histolyticum 0.58 mg injected into MP and/or PIP joints	Placebo Placebo (Sucrose and Tris) injection
Clinical Improvement in Non-Primary Joint After the Last Injection	70.8 Percentage of Joints	—

SECONDARY outcome

Timeframe: Baseline, Day 30 after last injection

Population: Includes evaluable non-primary joints treated with AA4500 with baseline fixed flexion contracture \>5° and at least 1 post-injection contracture measurement in subjects who received at least 1 non-primary joint injection in either study period

Percent change in degree of contracture of non-primary joint measured as 100 * (baseline contracture - last available post-injection contracture)/baseline contracture

Outcome measures

Measure	AA4500 0.58 mg n=89 Joints Collagenase clostridium histolyticum 0.58 mg injected into MP and/or PIP joints	Placebo Placebo (Sucrose and Tris) injection
Percent Reduction From Baseline Contracture of Non-Primary Joint After the Last Injection	66.4 Percentage of change Standard Deviation 34.63	—

SECONDARY outcome

Timeframe: Baseline, Day 30 after last injection

Population: Includes evaluable non-primary joints treated with AA4500 with baseline fixed flexion contracture \>5° and at least 1 post-injection contracture measurement in subjects who received at least 1 non-primary joint injection in either study period

Change in degree of range of motion in non-primary joint measured as last available post-injection range of motion - baseline range of motion

Outcome measures

Measure	AA4500 0.58 mg n=89 Joints Collagenase clostridium histolyticum 0.58 mg injected into MP and/or PIP joints	Placebo Placebo (Sucrose and Tris) injection
Change From Baseline Range of Motion in Non-Primary Joint After the Last Injection	25.2 Degrees Standard Deviation 16.80	—

SECONDARY outcome

Timeframe: Within 30 days after last injection

Population: Includes evaluable non-primary joints treated with AA4500 with baseline fixed flexion contracture \>5° and at least 1 post-injection contracture measurement in subjects who received at least 1 non-primary joint injection in either study period

Clinical success in non-primary joint defined as reduction in contracture to within 0-5° of normal within 30 days of injection, displayed in post injection time point categories

Outcome measures

Measure	AA4500 0.58 mg n=89 Joints Collagenase clostridium histolyticum 0.58 mg injected into MP and/or PIP joints	Placebo Placebo (Sucrose and Tris) injection
Time to Reach Clinical Success in Non-Primary Joint Injection 2, Day 7	2.2 Percentage of Joints	—
Time to Reach Clinical Success in Non-Primary Joint Injection 1, Day 1	6.7 Percentage of Joints	—
Time to Reach Clinical Success in Non-Primary Joint Injection 1, Day 7	18.0 Percentage of Joints	—
Time to Reach Clinical Success in Non-Primary Joint Injection 1, Day 30	11.2 Percentage of Joints	—
Time to Reach Clinical Success in Non-Primary Joint Injection 2, Day 0	0.0 Percentage of Joints	—
Time to Reach Clinical Success in Non-Primary Joint Injection 2, Day 1	9.0 Percentage of Joints	—
Time to Reach Clinical Success in Non-Primary Joint Injection 2, Day 30	4.5 Percentage of Joints	—
Time to Reach Clinical Success in Non-Primary Joint Injection 3, Day 0	0.0 Percentage of Joints	—
Time to Reach Clinical Success in Non-Primary Joint Injection 3, Day 1	0.0 Percentage of Joints	—
Time to Reach Clinical Success in Non-Primary Joint Injection 3, Day 7	0.0 Percentage of Joints	—
Time to Reach Clinical Success in Non-Primary Joint Injection 3, Day 30	2.2 Percentage of Joints	—
Time to Reach Clinical Success in Non-Primary Joint Did not reach Clinical Success	46.1 Percentage of Joints	—

SECONDARY outcome

Timeframe: Within 30 days after first injection

Population: Includes evaluable non-primary joints treated with AA4500 with baseline fixed flexion contracture \>5° and at least 1 post-injection contracture measurement in subjects who received at least 1 non-primary joint injection in either study period

Clinical success in non-primary joint defined as reduction in contracture to within 0-5° of normal within 30 days of injection.

Outcome measures

Measure	AA4500 0.58 mg n=89 Joints Collagenase clostridium histolyticum 0.58 mg injected into MP and/or PIP joints	Placebo Placebo (Sucrose and Tris) injection
Clinical Success in Non-Primary Joint After the First Injection	36.0 Percentage of Joints	—

SECONDARY outcome

Timeframe: Baseline, Within 30 days after first injection

Population: Includes evaluable non-primary joints treated with AA4500 with baseline fixed flexion contracture \>5° and at least 1 post-injection contracture measurement in subjects who received at least 1 non-primary joint injection in either study period

Clinical improvement in non-primary joint defined as ≥50% reduction from baseline in the degree of contracture within 30 days after injection

Outcome measures

Measure	AA4500 0.58 mg n=89 Joints Collagenase clostridium histolyticum 0.58 mg injected into MP and/or PIP joints	Placebo Placebo (Sucrose and Tris) injection
Clinical Improvement in Non-Primary Joint After the First Injection	58.4 Percentage of Joints	—

SECONDARY outcome

Timeframe: Baseline, Day 30 after first injection

Population: Includes evaluable non-primary joints treated with AA4500 with baseline fixed flexion contracture \>5° and at least 1 post-injection contracture measurement in subjects who received at least 1 non-primary joint injection in either study period

Percent change in degree of contracture of non-primary joint measured as 100 * (baseline contracture - last available post-injection contracture prior to next injection)/baseline contracture

Outcome measures

Measure	AA4500 0.58 mg n=89 Joints Collagenase clostridium histolyticum 0.58 mg injected into MP and/or PIP joints	Placebo Placebo (Sucrose and Tris) injection
Percent Reduction From Baseline Contracture of Non-Primary Joint After the First Injection	54.7 Percentage of change Standard Deviation 38.37	—

SECONDARY outcome

Timeframe: Baseline, Day 30 after first injection

Population: Includes evaluable non-primary joints treated with AA4500 with baseline fixed flexion contracture \>5° and at least 1 post-injection contracture measurement in subjects who received at least 1 non-primary joint injection in either study period

Change in degree of range of motion in non-primary joint measured as last available post-injection range of motion prior to the next injection - baseline range of motion

Outcome measures

Measure	AA4500 0.58 mg n=89 Joints Collagenase clostridium histolyticum 0.58 mg injected into MP and/or PIP joints	Placebo Placebo (Sucrose and Tris) injection
Change From Baseline Range of Motion in Non-Primary Joint After the First Injection	20.5 Degrees Standard Deviation 17.52	—

Adverse Events

AA4500 0.58 mg

Serious events: 7 serious events

Other events: 63 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Measure	AA4500 0.58 mg n=63 participants at risk collagenase clostridium histolyticum 0.58mg injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints	Placebo n=21 participants at risk Placebo injection is comprised of sucrose and Tris
Surgical and medical procedures Abdominal hernia repair	1.6% 1/63 • Number of events 1 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above)	0.00% 0/21 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above)
Cardiac disorders Atrial fibrillation	1.6% 1/63 • Number of events 1 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above)	0.00% 0/21 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above)
Hepatobiliary disorders Cholecystitis	1.6% 1/63 • Number of events 1 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above)	0.00% 0/21 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above)
Musculoskeletal and connective tissue disorders Dupuytren's contracture	1.6% 1/63 • Number of events 1 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above)	0.00% 0/21 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above)
Surgical and medical procedures Dupuytren's contracture operation	1.6% 1/63 • Number of events 1 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above)	0.00% 0/21 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above)
Social circumstances Inguinal hernia repair	0.00% 0/63 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above)	4.8% 1/21 • Number of events 1 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above)
Injury, poisoning and procedural complications Ligament injury	1.6% 1/63 • Number of events 1 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above)	0.00% 0/21 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above)
Eye disorders Orbital cyst	1.6% 1/63 • Number of events 1 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above)	0.00% 0/21 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above)
Infections and infestations Pneumonia	1.6% 1/63 • Number of events 1 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above)	0.00% 0/21 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above)
Nervous system disorders Sensory disturbance	1.6% 1/63 • Number of events 1 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above)	0.00% 0/21 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above)
Surgical and medical procedures Umbilical hernia repair	1.6% 1/63 • Number of events 1 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above)	0.00% 0/21 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above)

Other adverse events

Measure	AA4500 0.58 mg n=63 participants at risk collagenase clostridium histolyticum 0.58mg injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints	Placebo n=21 participants at risk Placebo injection is comprised of sucrose and Tris
Musculoskeletal and connective tissue disorders Axillary pain	12.7% 8/63 • Number of events 11 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above)	0.00% 0/21 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above)
Injury, poisoning and procedural complications Contusion	73.0% 46/63 • Number of events 136 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above)	9.5% 2/21 • Number of events 4 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above)
Nervous system disorders Dizziness	7.9% 5/63 • Number of events 5 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above)	0.00% 0/21 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above)
Renal and urinary disorders Haematuria	3.2% 2/63 • Number of events 2 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above)	9.5% 2/21 • Number of events 2 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above)
Nervous system disorders Headache	3.2% 2/63 • Number of events 2 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above)	9.5% 2/21 • Number of events 3 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above)
General disorders Injection site haemorrhage	42.9% 27/63 • Number of events 76 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above)	0.00% 0/21 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above)
General disorders Injection site pain	44.4% 28/63 • Number of events 61 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above)	9.5% 2/21 • Number of events 3 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above)
General disorders Injection site swelling	36.5% 23/63 • Number of events 55 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above)	14.3% 3/21 • Number of events 3 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above)
Blood and lymphatic system disorders Lymphadenopathy	20.6% 13/63 • Number of events 21 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above)	0.00% 0/21 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above)
General disorders Oedema peripheral	85.7% 54/63 • Number of events 163 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above)	9.5% 2/21 • Number of events 3 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above)
Musculoskeletal and connective tissue disorders Pain in extremity	57.1% 36/63 • Number of events 82 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above)	14.3% 3/21 • Number of events 4 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above)
Nervous system disorders Paraesthesia	7.9% 5/63 • Number of events 6 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above)	4.8% 1/21 • Number of events 3 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above)
Skin and subcutaneous tissue disorders Pruritus	20.6% 13/63 • Number of events 26 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above)	0.00% 0/21 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above)
General disorders Tenderness	31.7% 20/63 • Number of events 24 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above)	0.00% 0/21 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above)
Infections and infestations Upper respiratory tract infection	6.3% 4/63 • Number of events 5 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above)	9.5% 2/21 • Number of events 2 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above)
General disorders Injection site vesicles	7.9% 5/63 • Number of events 5 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above)	0.00% 0/21 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above)
Infections and infestations Lower respiratory tract infection	6.3% 4/63 • Number of events 4 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above)	0.00% 0/21 • Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study. This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide \& XIAFLEX Prescribing Information (see links above)

Additional Information

Clinical Trial Coordinator

Endo Pharmaceuticals Inc.

Email: clinicalsite.inquiries@endo.com

Results disclosure agreements

• Principal investigator is a sponsor employee Auxilium Pharmaceuticals, Inc. agreements may vary with individual investigators but will not prohibit any investigator from publishing. Auxilium supports the publication of results from all centers of a multicenter trial but requests that reports based on single site data not precede the primary publication of the entire clinical trial.
• Publication restrictions are in place

Restriction type: OTHER