Trial Outcomes & Findings for A Phase 3, Open-label Study of the Safety and Effectiveness of AA4500 Administered Twice Per Treatment Cycle for up to Four Treatment Cycles (2 x 4) in Men With Peyronie's Disease (NCT NCT01685437)

NCT ID: NCT01685437

Last Updated: 2017-10-05

Results Overview

A negative value in the percentage change from baseline in penile curvature deformity (angle measured in degrees) indicates less curvature.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 189 participants
• Primary outcome timeframe: Baseline and Week 36
• Results posted on: 2017-10-05

Participant Flow

Participant milestones

Measure	AA4500 collagenase clostridium histolyticum AA4500: 2 injections separated by approximately 24 hours to 72 hours, repeated after 42 days (± 5 days) for up to 4 treatment cycles
Overall Study STARTED	189
Overall Study COMPLETED	158
Overall Study NOT COMPLETED	31

Reasons for withdrawal

Measure	AA4500 collagenase clostridium histolyticum AA4500: 2 injections separated by approximately 24 hours to 72 hours, repeated after 42 days (± 5 days) for up to 4 treatment cycles
Overall Study Withdrawal by Subject	22
Overall Study Lost to Follow-up	3
Overall Study Adverse Event	1
Overall Study Protocol Violation	4
Overall Study Unable to make visits due to work	1

Baseline Characteristics

A Phase 3, Open-label Study of the Safety and Effectiveness of AA4500 Administered Twice Per Treatment Cycle for up to Four Treatment Cycles (2 x 4) in Men With Peyronie's Disease

Baseline characteristics by cohort

Measure	AA4500 n=189 Participants collagenase clostridium histolyticum AA4500: 2 injections separated by approximately 24 hours to 72 hours, repeated after 42 days (± 5 days) for up to 4 treatment cycles
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	134 Participants n=5 Participants
Age, Categorical >=65 years	55 Participants n=5 Participants
Age, Continuous	60.2 years STANDARD_DEVIATION 7.32 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	189 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	184 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants
Race (NIH/OMB) White	186 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Region of Enrollment United States	162 participants n=5 Participants
Region of Enrollment Australia	27 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Week 36

Population: Efficacy is based on modified intent-to-treat (mITT) population.

A negative value in the percentage change from baseline in penile curvature deformity (angle measured in degrees) indicates less curvature.

Outcome measures

Measure	AA4500 n=126 Participants collagenase clostridium histolyticum AA4500: 2 injections separated by approximately 24 hours to 72 hours, repeated after 42 days (± 5 days) for up to 4 treatment cycles
Percentage Change From Baseline in Penile Curvature	-36.3 percentage of curvature change Standard Deviation 30.72

PRIMARY outcome

Timeframe: Baseline and Week 36

Population: Efficacy is based on the mITT population.

Peyronie's disease bother score range 0 (no issue or not at all bothered) to 4 (extremely bothered) on 4 questions; total score range 0 to 16. A decrease in the change from baseline total score in the Peyronie's disease bother domain of the PDQ is indicated by a negative number.

Outcome measures

Measure	AA4500 n=126 Participants collagenase clostridium histolyticum AA4500: 2 injections separated by approximately 24 hours to 72 hours, repeated after 42 days (± 5 days) for up to 4 treatment cycles
Change From Baseline in the Peyronie's Disease Bother Domain of the Peyronie's Disease Questionnaire (PDQ)	-2.4 units on a scale Standard Deviation 3.34

SECONDARY outcome

Timeframe: Baseline and Week 36

Population: Efficacy is based on the mITT population.

Peyronie's disease symptoms (physical and psychological) severity score range 0 (none) to 4 (very severe) on 6 questions; total score range 0 to 24. A decrease in the change from baseline total score in the Peyronie's disease symptoms domain of the PDQ is indicated by a negative number.

Outcome measures

Measure	AA4500 n=126 Participants collagenase clostridium histolyticum AA4500: 2 injections separated by approximately 24 hours to 72 hours, repeated after 42 days (± 5 days) for up to 4 treatment cycles
Change From Baseline in the Severity of Peyronie's Disease Symptoms Domain of the PDQ	-2.9 units on a scale Standard Deviation 4.76

SECONDARY outcome

Timeframe: Baseline and Week 36

Population: Efficacy is based on the mITT population; this population only includes those subjects in the mITT population with a baseline penile pain score of 4 or greater.

Penile pain scale range 0 (no pain) to 10 (extreme pain) on 3 questions; total score range 0 to 30. A decrease in the change from baseline total score in the penile pain domain of the PDQ is indicated by a negative number. Subjects were required to have a penile pain score of 4 or greater at baseline.

Outcome measures

Measure	AA4500 n=36 Participants collagenase clostridium histolyticum AA4500: 2 injections separated by approximately 24 hours to 72 hours, repeated after 42 days (± 5 days) for up to 4 treatment cycles
Change From Baseline in the Penile Pain Domain of the PDQ in Subjects With Baseline Penile Pain Score ≥4	-4.5 units on a scale Standard Deviation 4.75

SECONDARY outcome

Timeframe: Week 36

Population: Efficacy is based on the mITT population.

Subject overall global assessment of Peyronie's disease score range -3 (much worse) to 3 (much improved). A score of 1 (improved in a small but important way), 2 (moderately improved), or 3 indicate a responder.

Outcome measures

Measure	AA4500 n=126 Participants collagenase clostridium histolyticum AA4500: 2 injections separated by approximately 24 hours to 72 hours, repeated after 42 days (± 5 days) for up to 4 treatment cycles
A Responder Analysis Based on Subject Overall Global Assessment Responder Status - No	32 participants
A Responder Analysis Based on Subject Overall Global Assessment Responder Status - Yes	94 participants

SECONDARY outcome

Timeframe: Baseline and Week 36

Population: Efficacy is based on the mITT population.

Overall satisfaction domain of the IIEF score range 0 to 5 on 2 questions where higher scores indicate improved function or satisfaction; total score range 0 to 10.

Outcome measures

Measure	AA4500 n=126 Participants collagenase clostridium histolyticum AA4500: 2 injections separated by approximately 24 hours to 72 hours, repeated after 42 days (± 5 days) for up to 4 treatment cycles
Change in the Overall Satisfaction Domain of the International Index of Erectile Function (IIEF)	0.7 units on a scale Standard Deviation 2.13

SECONDARY outcome

Timeframe: Baseline and Week 36

Population: Efficacy is based on the mITT population.

Penile plaque consistency score range 1 (non-palpable) to 5 (hard). A decrease in the change from baseline in penile plaque consistency is indicated by a negative number.

Outcome measures

Measure	AA4500 n=126 Participants collagenase clostridium histolyticum AA4500: 2 injections separated by approximately 24 hours to 72 hours, repeated after 42 days (± 5 days) for up to 4 treatment cycles
Change From Baseline in Penile Plaque Consistency	-0.4 units on a scale Standard Deviation 0.81

SECONDARY outcome

Timeframe: Week 36

Population: Composite responder analysis is based on the intent-to-treat (ITT) population.

A composite responder is indicated by

• a percent reduction from baseline in penile curvature greater than or equal to the threshold, and
• a reduction from baseline in Peyronie's disease bother score greater than or equal to the threshold, or change in the overall sexual activity within the last 3 months to having vaginal intercourse from no vaginal intercourse at screening.

Outcome measures

Measure	AA4500 n=189 Participants collagenase clostridium histolyticum AA4500: 2 injections separated by approximately 24 hours to 72 hours, repeated after 42 days (± 5 days) for up to 4 treatment cycles
A Composite Responder Analysis Based on Change From Baseline in Penile Curvature and in the Peyronie's Disease Bother Score No	85 participants
A Composite Responder Analysis Based on Change From Baseline in Penile Curvature and in the Peyronie's Disease Bother Score Yes	83 participants
A Composite Responder Analysis Based on Change From Baseline in Penile Curvature and in the Peyronie's Disease Bother Score Missing	21 participants

SECONDARY outcome

Timeframe: Baseline and Week 36

Population: Efficacy is based on the mITT population.

A negative value represents a reduction in measurement from baseline.

Outcome measures

Measure	AA4500 n=126 Participants collagenase clostridium histolyticum AA4500: 2 injections separated by approximately 24 hours to 72 hours, repeated after 42 days (± 5 days) for up to 4 treatment cycles
Change From Baseline in Penile Length	0.2 centimeters Standard Deviation 1.16

Adverse Events

AA4500

Serious events: 3 serious events

Other events: 178 other events

Deaths: 0 deaths

Serious adverse events

Measure	AA4500 n=189 participants at risk collagenase clostridium histolyticum AA4500: 2 injections separated by approximately 24 hours to 72 hours, repeated after 42 days (± 5 days) for up to 4 treatment cycles
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acoustic neuroma	0.53% 1/189 • Number of events 1
Gastrointestinal disorders Caecitis	0.53% 1/189 • Number of events 1
Renal and urinary disorders Calculus ureteric	0.53% 1/189 • Number of events 1

Other adverse events

Measure	AA4500 n=189 participants at risk collagenase clostridium histolyticum AA4500: 2 injections separated by approximately 24 hours to 72 hours, repeated after 42 days (± 5 days) for up to 4 treatment cycles
Reproductive system and breast disorders Penile haematoma	60.3% 114/189 • Number of events 271
Reproductive system and breast disorders Penile pain	33.9% 64/189 • Number of events 121
Reproductive system and breast disorders Penile swelling	30.2% 57/189 • Number of events 99
Reproductive system and breast disorders Penile oedema	24.3% 46/189 • Number of events 91
Reproductive system and breast disorders Penile haemorrhage	20.6% 39/189 • Number of events 73
General disorders Injection site haematoma	18.5% 35/189 • Number of events 66
General disorders Injection site pain	16.9% 32/189 • Number of events 50
General disorders Injection site haemorrhage	11.1% 21/189 • Number of events 56
General disorders Injection site swelling	10.6% 20/189 • Number of events 27
Injury, poisoning and procedural complications Contusion	9.0% 17/189 • Number of events 20

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