Clinical trial NCT00528606: AA4500 (XIAFLEX™, Proposed Name) in the Treatment of Dupuytren's Contracture
Official title: A Phase 3, Double-Blind, Randomized, Placebo-Controlled Study of the Safety and Efficacy of AA4500 in the Treatment of Subjects With Dupuytren's Contracture
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Dupuytren's Contracture
Lead sponsor: Endo Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2007-09-12
Enrollment: 308
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 was a Phase 3, double-blind, randomized, placebo-controlled study conducted in the United States. Subjects with a diagnosis of Dupuytren's contracture in a metacarpophalangeal (MP) or proximal interphalangeal (PIP) joint that resulted in a fixed flexion deformity of at least one finger, other than the thumb, that was at least 20° as measured by finger goniometry and was suitable for injection were randomized 2:1 to receive AA4500 0.58 mg or placebo.

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 Dupuytren's contracture, 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 that had never been treated with AA4500.
* Had a positive "table top test," defined as the inability to simultaneously place the affected finger(s) and palm flat against a table top.
* Judged to be in good health.

Exclusion Criteria:

* Had a chronic muscular, neurological, or neuromuscular disorder that affected the hands.
* Had received a treatment for Dupuytren's contracture, 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: Clinical Success (Reduction in Contracture to 5° or Less) of the Primary Joint After the Last Injection
timeFrame: Within 30 days after the last injection
Secondary outcomes:
measure: Clinical Improvement After the Last Injection
timeFrame: Baseline; within 30 days after the last injection
measure: Percent Reduction From Baseline Contracture After the Last Injection
timeFrame: Baseline; within 30 days after the last injection
measure: Change From Baseline Range of Motion After the Last Injection
timeFrame: Baselin; within 30 days after the last injection
measure: Time to First Achieve Success After the Last Injection
timeFrame: Last evaluation visit on which clinical success is achieved through the Day 30 evaluation
measure: Clinical Success (Reduction in Contracture to 5° or Less) After the First Injection
timeFrame: Within 30 days after first injection
measure: Clinical Improvement After the First Injection
timeFrame: Baseline; within 30 days after the first injection
measure: Percent Reduction From Baseline Contracture After the First Injection
timeFrame: Baseline, within 30 days after the first injection
measure: Change From Baseline Range of Motion After the First Injection
timeFrame: Baseline; within 30 days after the first injection
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: 100 UCLA Medical Plaza, Suite 305
state: California
city: Palo Alto
country: United States
facility: Hand Surgery Clinic
state: California
city: Denver
country: United States
facility: Hand Surgery Associates, PC
state: Colorado
city: Atlanta
country: United States
facility: The Hand and Upper Extremity Center of Georgia, P.C.
state: Georgia
city: Rockford
country: United States
facility: Rockford Orthopedic Associates, Ltd.
state: Illinois
city: Indianapolis
country: United States
facility: The Indiana Hand Center
state: Indiana
city: Boston
country: United States
facility: Brigham and Women's Hospital, Department of Orthopedic Surgery
state: Massachusetts
city: Newton
country: United States
facility: Newton-Wellesley Hospital
state: Massachusetts
city: Minneapolis
country: United States
facility: TRIA Orthopaedic Center
state: Minnesota
city: New York
country: United States
facility: Hospital for Special Surgery
state: New York
city: Stony Brook
country: United States
facility: SUNY Stony Brook - Department of Orthopedics
state: New York
city: Oklahoma City
country: United States
facility: Health Research Institute
state: Oklahoma
city: Erie
country: United States
facility: Hand Microsurgery & Reconstructive Orthopaedics
state: Pennsylvania
city: State College
country: United States
facility: University Orthopedics Center
state: Pennsylvania
city: Providence
country: United States
facility: Department of Orthopaedics, Brown University, Rhode Island Hospital
state: Rhode Island
Study officials:
affiliation: Endo Pharmaceuticals
name: Veronica Urdaneta, MD
role: STUDY_DIRECTOR
References:
citation: Witthaut J, Bushmakin AG, Gerber RA, Cappelleri JC, Le Graverand-Gastineau MP. Determining clinically important changes in range of motion in patients with Dupuytren's Contracture: secondary analysis of the randomized, double-blind, placebo-controlled CORD I study. Clin Drug Investig. 2011 Nov 1;31(11):791-8. doi: 10.1007/BF03256918.
citation: Hurst LC, Badalamente MA, Hentz VR, Hotchkiss RN, Kaplan FT, Meals RA, Smith TM, Rodzvilla J; CORD I Study Group. Injectable collagenase clostridium histolyticum for Dupuytren's contracture. N Engl J Med. 2009 Sep 3;361(10):968-79. doi: 10.1056/NEJMoa0810866.