Trial Outcomes & Findings for A Study of AA4500 in Men With Peyronie's Disease (NCT NCT01243411)

NCT ID: NCT01243411

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: 348 participants
• Primary outcome timeframe: Baseline and Week 36
• Results posted on: 2017-10-05

Participant Flow

Includes all subjects who were enrolled and received at least 1 dose of study drug; subjects who were enrolled but not treated were excluded from the population

Participant milestones

Measure	AA4500 collagenase clostridium histolyticum AA4500: 2 injections separated by at least 24 hours but not more than 72 hours, repeated after 42 days (± 5 days) for up to 4 treatment cycles (ie, total of up to 8 injections per subject)
Overall Study STARTED	347
Overall Study COMPLETED	306
Overall Study NOT COMPLETED	41

Reasons for withdrawal

Measure	AA4500 collagenase clostridium histolyticum AA4500: 2 injections separated by at least 24 hours but not more than 72 hours, repeated after 42 days (± 5 days) for up to 4 treatment cycles (ie, total of up to 8 injections per subject)
Overall Study Withdrawal by Subject	18
Overall Study Lost to Follow-up	10
Overall Study Adverse Event	5
Overall Study Other	8

Baseline Characteristics

A Study of AA4500 in Men With Peyronie's Disease

Baseline characteristics by cohort

Measure	AA4500 n=347 Participants collagenase clostridium histolyticum AA4500: 2 injections separated by at least 24 hours but not more than 72 hours, repeated after 42 days (± 5 days) for up to 4 treatment cycles (ie, total of up to 8 injections per subject)
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	289 Participants n=5 Participants
Age, Categorical >=65 years	58 Participants n=5 Participants
Age, Continuous	56.5 years STANDARD_DEVIATION 9.0 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	347 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	22 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	325 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	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	4 Participants n=5 Participants
Race (NIH/OMB) White	333 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	8 Participants n=5 Participants
Region of Enrollment France	13 participants n=5 Participants
Region of Enrollment United States	102 participants n=5 Participants
Region of Enrollment Spain	21 participants n=5 Participants
Region of Enrollment Denmark	42 participants n=5 Participants
Region of Enrollment Germany	41 participants n=5 Participants
Region of Enrollment Italy	24 participants n=5 Participants
Region of Enrollment United Kingdom	17 participants n=5 Participants
Region of Enrollment New Zealand	54 participants n=5 Participants
Region of Enrollment Sweden	33 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Week 36

Population: Efficacy is based on the 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=238 Participants collagenase clostridium histolyticum AA4500: 2 injections separated by at least 24 hours but not more than 72 hours, repeated after 42 days (± 5 days) for up to 4 treatment cycles (ie, total of up to 8 injections per subject)
Percentage Change From Baseline in Penile Curvature	-34.4 percentage of curvature change Standard Deviation 25.21

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=238 Participants collagenase clostridium histolyticum AA4500: 2 injections separated by at least 24 hours but not more than 72 hours, repeated after 42 days (± 5 days) for up to 4 treatment cycles (ie, total of up to 8 injections per subject)
Change From Baseline in the Peyronie's Disease Bother Domain of the Peyronie's Disease Questionnaire (PDQ)	-3.3 units on a scale Standard Deviation 3.46

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=238 Participants collagenase clostridium histolyticum AA4500: 2 injections separated by at least 24 hours but not more than 72 hours, repeated after 42 days (± 5 days) for up to 4 treatment cycles (ie, total of up to 8 injections per subject)
Change From Baseline in the Severity of Peyronie's Disease Symptoms Domain of the PDQ	-4.2 units on a scale Standard Deviation 5.14

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=114 Participants collagenase clostridium histolyticum AA4500: 2 injections separated by at least 24 hours but not more than 72 hours, repeated after 42 days (± 5 days) for up to 4 treatment cycles (ie, total of up to 8 injections per subject)
Change From Baseline in the Penile Pain Domain of the PDQ in Subjects With Baseline Penile Pain Score ≥4	-5.3 units on a scale Standard Deviation 4.93

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=238 Participants collagenase clostridium histolyticum AA4500: 2 injections separated by at least 24 hours but not more than 72 hours, repeated after 42 days (± 5 days) for up to 4 treatment cycles (ie, total of up to 8 injections per subject)
A Responder Analysis Based on Subject Overall Global Assessment Responder Status - Yes	172 participants
A Responder Analysis Based on Subject Overall Global Assessment Responder Status - No	66 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=238 Participants collagenase clostridium histolyticum AA4500: 2 injections separated by at least 24 hours but not more than 72 hours, repeated after 42 days (± 5 days) for up to 4 treatment cycles (ie, total of up to 8 injections per subject)
Change in the Overall Satisfaction Domain of the International Index of Erectile Function (IIEF)	1.1 units on a scale Standard Deviation 2.23

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=238 Participants collagenase clostridium histolyticum AA4500: 2 injections separated by at least 24 hours but not more than 72 hours, repeated after 42 days (± 5 days) for up to 4 treatment cycles (ie, total of up to 8 injections per subject)
Change From Baseline in Penile Plaque Consistency	-0.8 units on a scale Standard Deviation 0.93

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=347 Participants collagenase clostridium histolyticum AA4500: 2 injections separated by at least 24 hours but not more than 72 hours, repeated after 42 days (± 5 days) for up to 4 treatment cycles (ie, total of up to 8 injections per subject)
A Composite Responder Analysis Based on Change From Baseline in Penile Curvature and in the Peyronie's Disease Bother Score Responder - Yes	177 participants
A Composite Responder Analysis Based on Change From Baseline in Penile Curvature and in the Peyronie's Disease Bother Score Responder - No	140 participants
A Composite Responder Analysis Based on Change From Baseline in Penile Curvature and in the Peyronie's Disease Bother Score Responder - Missing	30 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=238 Participants collagenase clostridium histolyticum AA4500: 2 injections separated by at least 24 hours but not more than 72 hours, repeated after 42 days (± 5 days) for up to 4 treatment cycles (ie, total of up to 8 injections per subject)
Change From Baseline in Penile Length	0.4 centimeters Standard Deviation 1.11

Adverse Events

AA4500

Serious events: 13 serious events

Other events: 297 other events

Deaths: 0 deaths

Serious adverse events

Measure	AA4500 n=347 participants at risk collagenase clostridium histolyticum AA4500: 2 injections separated by at least 24 hours but not more than 72 hours, repeated after 42 days (± 5 days) for up to 4 treatment cycles (ie, total of up to 8 injections per subject)
Reproductive system and breast disorders Penile haematoma	0.58% 2/347
Gastrointestinal disorders Inguinal hernia	0.29% 1/347
Injury, poisoning and procedural complications Tendon rupture	0.29% 1/347
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.58% 2/347
Vascular disorders Deep vein thrombosis	0.29% 1/347
Cardiac disorders Acute myocardial infarction	0.29% 1/347
General disorders Device occlusion	0.29% 1/347
Injury, poisoning and procedural complications Fracture of penis	0.29% 1/347
Renal and urinary disorders Nephrolithiasis	0.29% 1/347
Psychiatric disorders Mania	0.29% 1/347
Injury, poisoning and procedural complications Joint injury	0.29% 1/347
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.29% 1/347

Other adverse events

Measure	AA4500 n=347 participants at risk collagenase clostridium histolyticum AA4500: 2 injections separated by at least 24 hours but not more than 72 hours, repeated after 42 days (± 5 days) for up to 4 treatment cycles (ie, total of up to 8 injections per subject)
Reproductive system and breast disorders Penile haematoma	51.3% 178/347 • Number of events 356
Reproductive system and breast disorders Penile pain	34.6% 120/347 • Number of events 261
General disorders Injection site pain	26.8% 93/347 • Number of events 171
Reproductive system and breast disorders Penile swelling	26.2% 91/347 • Number of events 138
General disorders Injection site haematoma	24.2% 84/347 • Number of events 139
Reproductive system and breast disorders Penile haemorrhage	22.8% 79/347 • Number of events 203
Reproductive system and breast disorders Penile oedema	14.1% 49/347 • Number of events 120
General disorders Injection site swelling	11.5% 40/347 • Number of events 68
Reproductive system and breast disorders Painful erection	5.5% 19/347 • 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