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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01243411




Registration number
NCT01243411
Ethics application status
Date submitted
17/11/2010
Date registered
18/11/2010
Date last updated
5/10/2017

Titles & IDs
Public title
A Study of AA4500 in Men With Peyronie's Disease
Scientific title
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
Secondary ID [1] 0 0
AUX-CC-802
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Peyronie's Disease 0 0
Condition category
Condition code
Renal and Urogenital 0 0 0 0
Other renal and urogenital disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - AA4500

Experimental: AA4500 - collagenase clostridium histolyticum


Other interventions: 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)

Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage Change From Baseline in Penile Curvature - A negative value in the percentage change from baseline in penile curvature deformity (angle measured in degrees) indicates less curvature.
Timepoint [1] 0 0
Baseline and Week 36
Primary outcome [2] 0 0
Change From Baseline in the Peyronie's Disease Bother Domain of the Peyronie's Disease Questionnaire (PDQ) - 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.
Timepoint [2] 0 0
Baseline and Week 36
Secondary outcome [1] 0 0
Change From Baseline in the Severity of Peyronie's Disease Symptoms Domain of the PDQ - 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.
Timepoint [1] 0 0
Baseline and Week 36
Secondary outcome [2] 0 0
Change From Baseline in the Penile Pain Domain of the PDQ in Subjects With Baseline Penile Pain Score =4 - 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.
Timepoint [2] 0 0
Baseline and Week 36
Secondary outcome [3] 0 0
A Responder Analysis Based on Subject Overall Global Assessment - 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.
Timepoint [3] 0 0
Week 36
Secondary outcome [4] 0 0
Change in the Overall Satisfaction Domain of the International Index of Erectile Function (IIEF) - 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.
Timepoint [4] 0 0
Baseline and Week 36
Secondary outcome [5] 0 0
Change From Baseline in Penile Plaque Consistency - 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.
Timepoint [5] 0 0
Baseline and Week 36
Secondary outcome [6] 0 0
A Composite Responder Analysis Based on Change From Baseline in Penile Curvature and in the Peyronie's Disease Bother Score - 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.
Timepoint [6] 0 0
Week 36
Secondary outcome [7] 0 0
Change From Baseline in Penile Length - A negative value represents a reduction in measurement from baseline.
Timepoint [7] 0 0
Baseline and Week 36

Eligibility
Key inclusion criteria
No subject should be enrolled until all eligibility criteria have been satisfied. Subjects
who receive placebo in a previous Auxilium-sponsored study may enroll in this study
provided they continue to meet the eligibility requirements. To qualify for the study a
subject must:

1. Be a male and be = 18 years of age

2. Be in a stable relationship with a female partner/spouse for at least 3 months before
screening and be willing to have vaginal intercourse with that partner/spouse

3. Have symptom(s) of Peyronie's disease for at least 12 months before the first dose of
study drug and have evidence of stable disease as determined by the investigator

4. Have penile curvature of at least 30° in the dorsal, lateral, or dorsal/lateral plane
at screening. It must be possible to delineate the single plane of maximal curvature
for evaluation during the study

5. Be judged to be in good health, based upon the results of a medical history, physical
examination, and laboratory profile

6. Voluntarily sign and date an informed consent agreement approved by the Institutional
Review Board/Independent Ethics Committee (IRB/IEC). The subject must also sign an
authorization form to allow disclosure of his protected health information (PHI). The
PHI authorization form and informed consent form may be an integrated form or may be
separate forms depending on the institution

7. Be able to read, complete and understand the various rating instruments in English or
the appropriate local language for the country in which the study is being performed.

-
Minimum age
18 Years
Maximum age
No limit
Gender
Males
Can healthy volunteers participate?
No
Key exclusion criteria
A subject will be excluded from study participation if he:

1. Has a penile curvature of less than 30° or greater than 90° at the screening visit

2. Has any of the following conditions:

- Chordee in the presence or absence of hypospadias

- Thrombosis of the dorsal penile artery and/or vein

- Infiltration by a benign or malignant mass resulting in penile curvature

- Infiltration by an infectious agent, such as lymphogranuloma venereum

- Ventral curvature from any cause

- Presence of an active sexually transmitted disease

- Known active hepatitis B or C

- Known immune deficiency disease or be positive for human immunodeficiency virus
(HIV)

3. Has previously undergone surgery for Peyronie's disease

4. Fails to have an erection which in the opinion of the investigator is sufficient to
accurately measure the subject's penile deformity after administration of
prostaglandin E1 or trimix

5. Has a calcified plaque as evident by appropriate radiographic evaluation, penile x-ray
or penile ultrasound that would prevent proper injection of study medication (penile
ultrasound only in EU countries). Non-contiguous stippling of calcium is acceptable
for inclusion provided the calcium deposit does not interfere with the injection of
AA4500 into the plaque

6. Has an isolated hourglass deformity of the penis

7. Has the plaque causing curvature of the penis located proximal to the base of the
penis, so that the injection of the local anesthetic would interfere with the
injection of AA4500 into the plaque

8. Has previously received alternative medical therapies for Peyronie's disease
administered by the intralesional route (including, but not limited to, steroids,
verapamil, and the naturally occurring low molecular weight protein, interferon-a2b)
within 3 months before the first dose of study drug or plans to use any of these
medical therapies at any time during the study

9. Has received alternative medical therapies for Peyronie's disease administered by the
oral (including, but not limited to, vitamin E [> 500 U], potassium aminobenzoate
[Potaba], tamoxifen, colchicine, pentoxifylline, over-the-counter erectile dysfunction
medications, or steroidal anti-inflammatory drugs) or topical routes (including, but
not limited to, verapamil applied as a cream) within 3 months before the first dose of
study drug or plans to use any of these medical therapies at any time during the study

10. Has had extracorporeal shock wave therapy (ESWT) for the correction of Peyronie's
disease within the 6-month period before screening or plans to have ESWT at any time
during the study

11. Has used any mechanical type device for correction of Peyronie's disease within the
2-week period before screening or plans to use any these devices at any time during
the study

12. Has used a mechanical device to induce a passive erection within the 2-week period
before screening or plans to use any of these devices at any time during the study

13. Has significant erectile dysfunction that has failed to respond to oral treatment with
phosphodiesterase type 5 (PDE5) inhibitors

14. Has a penile Duplex Doppler ultrasound evaluation at screening that shows compromised
penile hemodynamics that in the opinion of the investigator is clinically significant

15. Has uncontrolled hypertension, as determined by the investigator

16. Has a known recent history of stroke, bleeding, or other significant medical
condition, which in the investigator's opinion would make the subject unsuitable for
enrollment in the study

17. Is unwilling or unable to cooperate with the requirements of the study including
completion of all scheduled study visits

18. Has received an investigational drug or treatment within 30 days before the first dose
of study drug, except for subjects who receive one treatment cycle of AA4500 in Study
AUX-CC-805

19. Has a known systemic allergy to collagenase or any other excipient of AA4500

20. Has a known allergy to any concomitant medication required as per the protocol

21. Has received anticoagulant medication (except for = 165 mg aspirin daily or = 800 mg
of over-the-counter NSAIDS daily) during the 7 days before each dose of study drug

22. Has received any collagenase treatments within 30 days of the first dose of study
drug, except for subjects who receive one treatment cycle of AA4500 in Study
AUX-CC-805

23. Has, at any time, received AA4500 for the treatment of Peyronie's disease, except for
subjects who receive one treatment cycle of AA4500 in Study AUX-CC-805

Study design
Purpose of the study
Treatment
Allocation to intervention
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Connecticut
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Indiana
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
Ohio
Country [8] 0 0
United States of America
State/province [8] 0 0
Pennsylvania
Country [9] 0 0
United States of America
State/province [9] 0 0
Virginia
Country [10] 0 0
Denmark
State/province [10] 0 0
Aalborg
Country [11] 0 0
Denmark
State/province [11] 0 0
Frederiksberg
Country [12] 0 0
Denmark
State/province [12] 0 0
Frederikssund
Country [13] 0 0
Denmark
State/province [13] 0 0
Gentofte
Country [14] 0 0
France
State/province [14] 0 0
Lyon
Country [15] 0 0
France
State/province [15] 0 0
Saint Genis Laval
Country [16] 0 0
Germany
State/province [16] 0 0
Freiburg
Country [17] 0 0
Germany
State/province [17] 0 0
Hamburg
Country [18] 0 0
Germany
State/province [18] 0 0
Marburg
Country [19] 0 0
Germany
State/province [19] 0 0
Reutlingen
Country [20] 0 0
Germany
State/province [20] 0 0
Tubingen
Country [21] 0 0
Italy
State/province [21] 0 0
Naples
Country [22] 0 0
Italy
State/province [22] 0 0
Rome
Country [23] 0 0
New Zealand
State/province [23] 0 0
Auckland
Country [24] 0 0
New Zealand
State/province [24] 0 0
Bay of Plenty
Country [25] 0 0
New Zealand
State/province [25] 0 0
Canterbury
Country [26] 0 0
New Zealand
State/province [26] 0 0
Northland
Country [27] 0 0
New Zealand
State/province [27] 0 0
Wellington
Country [28] 0 0
Spain
State/province [28] 0 0
Barcelona
Country [29] 0 0
Spain
State/province [29] 0 0
Madrid
Country [30] 0 0
Sweden
State/province [30] 0 0
Goteborg
Country [31] 0 0
Sweden
State/province [31] 0 0
Karlshamn
Country [32] 0 0
Sweden
State/province [32] 0 0
Uppsala
Country [33] 0 0
United Kingdom
State/province [33] 0 0
London
Country [34] 0 0
United Kingdom
State/province [34] 0 0
Sunderland

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Endo Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This study is a Phase 3, open-label study of the safety and efficacy of AA4500 0.58 mg in
subjects with Peyronie's disease. Subjects will be screened for study eligibility within 21
days before the initial injection of study drug in the first treatment cycle.

After up to four treatment cycles, each subject will be followed for additional safety and
efficacy assessments on Days 168 (± 7 days) and 252 (± 7 days) (nominal weeks 24 and 36).

After the final injection of each treatment cycle, the investigator will model the plaque in
an attempt to stretch or elongate the plaque. If the subject's penile curvature is reduced to
<15° after the first, second, or third cycle of injections or if the investigator determines
further treatment is not clinically indicated (eg, adverse events; allergic reaction),
subsequent treatment cycles will not be administered.

Approximately 300 subjects will be enrolled.
Trial website
https://clinicaltrials.gov/show/NCT01243411
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Gregory J. Kaufman, MD
Address 0 0
Auxilium Pharmaceuticals, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications