Clinical trial NCT00533273: Non-US Study of AA4500 (XIAFLEX™, Proposed Name) in the Treatment of Advanced Dupuytren's Disease
Official title: A Phase 3, Double-Blind, Randomized, Placebo-Controlled Study of the Safety and Efficacy of AA4500 in the Treatment of Subjects With Advanced Dupuytren's Disease Followed by an Open-Label Extension Phase
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Advanced Dupuytren's Disease
Lead sponsor: Endo Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2007-09-21
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This 12-month study had two phases: a 90-day double-blind, randomized, placebo-controlled phase and a nine-month open-label extension phase. Before treatment, eligible subjects were stratified by the primary joint type (30 metacarpophalangeal \[MP\] joints and 30 proximal interphalangeal \[PIP\] joints) and by severity of the primary joint contracture (ie, up to 50° or \>50° for MP joints and up to 40° or \>40° for PIP joints) and then randomized in a 2:1 ratio to either AA4500 0.58 mg or placebo. Upon completion of the double-blind phase (ie, 90-day evaluation after the first injection), all subjects were eligible to enter the open-label extension phase of the study in which they were followed for an additional nine months. Subjects who required further treatment because they either did not achieve reduction in contracture to 5° or less, the cord affecting the primary joint received placebo, another cord received less than three injections of AA4500, or they had untreated cords that were affecting other joints had the option to receive up to five additional injections of AA4500 0.58 mg in the open-label extension phase, with individual cords receiving up to three injections of AA4500.

This study was designed to be part of the larger clinical program, for adult patients with Dupuytren's contracture with a palpable cord, where the data from 2 pivotal Placebo-Controlled studies (AUX-CC-857 \[NCT00528606\] and AUX-CC-859 \[NCT00533273\]) and 7 non-pivotal studies were evaluated.


Eligibility criteria: Inclusion Criteria:

* Subjects with a diagnosis of advanced Dupuytren's disease, with a fixed flexion deformity of at least one finger, other than the thumb, that had a contracture at least 20°, but not greater than 100°, for MP (80° for PIP) joints, caused by a palpable cord.
* Had a positive "table top test," defined as the inability to simultaneously place the affected finger(s) and palm flat against a table top.
* Were naive to AA4500 treatment
* Were judged to be in good health, based upon the results of a medical history, physical examination, and safety laboratory profile.

Exclusion Criteria:

* Had a chronic muscular, neurological, or neuromuscular disorder that affected the hands.
* Had received a treatment for advanced Dupuytren's disease, including surgery (fasciectomy or surgical fasciotomy), needle aponeurotomy/fasciotomy, or injection of verapamil and/or interferon on the selected primary joint within 90 days before the first dose of study drug.
* Had a known recent history of stroke, bleeding, a disease process that affected the hands, or other medical condition, which in the investigator's opinion, would make the subject unsuitable for enrollment in the study.

Primary outcomes:
measure: Reduction in Primary Joint Contracture to 5° or Less
timeFrame: Within 30 days after last injection
Secondary outcomes:
measure: Clinical Improvement in Primary Joint After the Last Injection
timeFrame: Baseline, Within 30 days after last injection
measure: Percent Reduction From Baseline Contracture of Primary Joint After the Last Injection
timeFrame: Baseline, Day 30 after last injection
measure: Change From Baseline Range of Motion in Primary Joint After the Last Injection
timeFrame: Baseline, Day 30 after last injection
measure: Time to Reach Clinical Success in Primary Joint
timeFrame: Within 30 days after last injection
measure: Clinical Success in Primary Joint After the First Injection
timeFrame: Within 30 days after first injection
measure: Clinical Improvement in Primary Joint After the First Injection
timeFrame: Baseline, Within 30 days after first injection
measure: Percent Reduction From Baseline Contracture of Primary Joint After the First Injection
timeFrame: Baseline, Day 30 after first injection
measure: Change From Baseline Range of Motion in Primary Joint After the First Injection
timeFrame: Baseline, Day 30 after first injection
measure: Reduction in Non-primary Joint Contracture to 5° or Less After the Last Injection
timeFrame: Within 30 days after last injection
measure: Clinical Improvement in Non-Primary Joint After the Last Injection
timeFrame: Baseline, Within 30 days after last injection
measure: Percent Reduction From Baseline Contracture of Non-Primary Joint After the Last Injection
timeFrame: Baseline, Day 30 after last injection
measure: Change From Baseline Range of Motion in Non-Primary Joint After the Last Injection
timeFrame: Baseline, Day 30 after last injection
measure: Time to Reach Clinical Success in Non-Primary Joint
timeFrame: Within 30 days after last injection
measure: Clinical Success in Non-Primary Joint After the First Injection
timeFrame: Within 30 days after first injection
measure: Clinical Improvement in Non-Primary Joint After the First Injection
timeFrame: Baseline, Within 30 days after first injection
measure: Percent Reduction From Baseline Contracture of Non-Primary Joint After the First Injection
timeFrame: Baseline, Day 30 after first injection
measure: Change From Baseline Range of Motion in Non-Primary Joint After the First Injection
timeFrame: Baseline, Day 30 after first injection
Other outcomes:
Locations:
city: Auchenflower
country: Australia
facility: Rivercity Research
state: Queensland
city: Brisbane
country: Australia
facility: Brisbane Hand & Upper Limb Clinic
state: Queensland
city: Caboolture
country: Australia
facility: Caboolture Clinical Research Centre
state: Queensland
city: Kippa Ring
country: Australia
facility: Peninsula Clinical Research Centre
state: Queensland
city: Hobart
country: Australia
facility: Menzies Reserarch Institute
state: Tasmania
city: Malvern
country: Australia
facility: Emeritus Research
state: Victoria
city: Shenton Park
country: Australia
facility: Royal Perth Hospital
state: Western Australia
Study officials:
affiliation: Endo Pharmaceuticals
name: Veronica Urdaneta, MD
role: STUDY_DIRECTOR
References: