AA4500 (XIAFLEX™, Proposed Name) in the Treatment of Dupuytren's Contracture

Endo Pharmaceuticals308 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

308

Conditions

Dupuytren's Contracture

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (15)

100 UCLA Medical Plaza, Suite 305

Los Angeles, California, United States

Hand Surgery Clinic

Palo Alto, California, United States

Hand Surgery Associates, PC

Denver, Colorado, United States

The Hand and Upper Extremity Center of Georgia, P.C.

Atlanta, Georgia, United States

Rockford Orthopedic Associates, Ltd.

Rockford, Illinois, United States

The Indiana Hand Center

Indianapolis, Indiana, United States

Brigham and Women's Hospital, Department of Orthopedic Surgery

Boston, Massachusetts, United States

Newton-Wellesley Hospital

Newton, Massachusetts, United States

TRIA Orthopaedic Center

Minneapolis, Minnesota, United States

Hospital for Special Surgery

New York, New York, United States

...and 5 more locations

Outcomes

Primary Outcomes

Clinical Success (Reduction in Contracture to 5° or Less) of the Primary Joint After the Last Injection

The Primary Outcome Measure for patients treated with AA4500 is the percentage of joints that were successfully treated where "successfully treated" was defined as reduction in contracture to within 0-5° of normal within 30 days of injection. The Primary Outcome Measure for placebo treated patients is the percentage of joints that were successfully treated where "successfully treated" was defined as reduction in contracture to within 0-5° of normal within 30 days of injection.

Time frame: Within 30 days after the last injection

Secondary Outcomes

Clinical Improvement After the Last Injection

Clinical Improvement is defined as \>= 50% reduction from baseline in degree of contracture within 30 days of the injection.

Time frame: Baseline; within 30 days after the last injection

Percent Reduction From Baseline Contracture After the Last Injection

Percent change in degree of contracture measured as 100\* (baseline contracture - last available post-injection contracture)/baseline contracture.

Time frame: Baseline; within 30 days after the last injection

Change From Baseline Range of Motion After the Last Injection

Change in degree of motion measured as last available post-injection range of motion - baseline range of motion.

Time frame: Baselin; within 30 days after the last injection

Time to First Achieve Success After the Last Injection

Time frame: Last evaluation visit on which clinical success is achieved through the Day 30 evaluation

Clinical Success (Reduction in Contracture to 5° or Less) After the First Injection

Clinical Success is defined as reduction in contracture to within 0-5 degrees of normal within 30 days of injection.

Time frame: Within 30 days after first injection

Clinical Improvement After the First Injection

Clinical Improvement is defined as \>= 50% reduction from contracture within 30 days of the first injectionor greater of baseline contracture within 30 days of the injection.

Time frame: Baseline; within 30 days after the first injection

Percent Reduction From Baseline Contracture After the First Injection

Percent change in degree of contracture measured as 100\* (baseline contracture - last available post-injection contracture)/baseline contracture.

Time frame: Baseline, within 30 days after the first injection

Change From Baseline Range of Motion After the First Injection

Change in degree of motion measured as last available post-injection range of motion - baseline range of motion.

Time frame: Baseline; within 30 days after the first injection