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

Primary Purpose

Dupuytren's Contracture

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
collagenase clostridium histolyticum
Placebo
Sponsored by
Endo Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Dupuytren's Contracture

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • 100 UCLA Medical Plaza, Suite 305
  • Hand Surgery Clinic
  • Hand Surgery Associates, PC
  • The Hand and Upper Extremity Center of Georgia, P.C.
  • Rockford Orthopedic Associates, Ltd.
  • The Indiana Hand Center
  • Brigham and Women's Hospital, Department of Orthopedic Surgery
  • Newton-Wellesley Hospital
  • TRIA Orthopaedic Center
  • Hospital for Special Surgery
  • SUNY Stony Brook - Department of Orthopedics
  • Health Research Institute
  • Hand Microsurgery & Reconstructive Orthopaedics
  • University Orthopedics Center
  • Department of Orthopaedics, Brown University, Rhode Island Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

AA4500 0.58 mg

Placebo

Arm Description

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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 to First Achieve Success After the Last Injection
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.
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.
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.
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.

Full Information

First Posted
September 11, 2007
Last Updated
October 26, 2017
Sponsor
Endo Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT00528606
Brief Title
AA4500 (XIAFLEX™, Proposed Name) in the Treatment of Dupuytren's Contracture
Acronym
CORD-I
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

2. Study Status

Record Verification Date
October 2017
Overall Recruitment Status
Completed
Study Start Date
August 2007 (Actual)
Primary Completion Date
April 2008 (Actual)
Study Completion Date
April 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Endo Pharmaceuticals

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dupuytren's Contracture

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
308 (Actual)

8. Arms, Groups, and Interventions

Arm Title
AA4500 0.58 mg
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Biological
Intervention Name(s)
collagenase clostridium histolyticum
Other Intervention Name(s)
XIAFLEX®, AA4500
Intervention Description
Subjects could have received up to three injections of AA4500 into the cord of the affected hand. Each injection was separated by at least 30 days. Individual cords may have received up to a maximum of three injections.
Intervention Type
Biological
Intervention Name(s)
Placebo
Intervention Description
Subjects could have received up to three injections of placebo into the cord of the affected hand. Each injection was separated by at least 30 days. Individual cords may have received up to a maximum of three injections.
Primary Outcome Measure Information:
Title
Clinical Success (Reduction in Contracture to 5° or Less) of the Primary Joint After the Last Injection
Description
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 Outcome Measure Information:
Title
Clinical Improvement After the Last Injection
Description
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
Title
Percent Reduction From Baseline Contracture After the Last Injection
Description
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
Title
Change From Baseline Range of Motion After the Last Injection
Description
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
Title
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
Title
Clinical Success (Reduction in Contracture to 5° or Less) After the First Injection
Description
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
Title
Clinical Improvement After the First Injection
Description
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
Title
Percent Reduction From Baseline Contracture After the First Injection
Description
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
Title
Change From Baseline Range of Motion After the First Injection
Description
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Veronica Urdaneta, MD
Organizational Affiliation
Endo Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
100 UCLA Medical Plaza, Suite 305
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Hand Surgery Clinic
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
Hand Surgery Associates, PC
City
Denver
State/Province
Colorado
ZIP/Postal Code
80210
Country
United States
Facility Name
The Hand and Upper Extremity Center of Georgia, P.C.
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30342
Country
United States
Facility Name
Rockford Orthopedic Associates, Ltd.
City
Rockford
State/Province
Illinois
ZIP/Postal Code
61107
Country
United States
Facility Name
The Indiana Hand Center
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46260
Country
United States
Facility Name
Brigham and Women's Hospital, Department of Orthopedic Surgery
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Newton-Wellesley Hospital
City
Newton
State/Province
Massachusetts
ZIP/Postal Code
02462
Country
United States
Facility Name
TRIA Orthopaedic Center
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55431
Country
United States
Facility Name
Hospital for Special Surgery
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
SUNY Stony Brook - Department of Orthopedics
City
Stony Brook
State/Province
New York
ZIP/Postal Code
11794
Country
United States
Facility Name
Health Research Institute
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73109
Country
United States
Facility Name
Hand Microsurgery & Reconstructive Orthopaedics
City
Erie
State/Province
Pennsylvania
ZIP/Postal Code
16550
Country
United States
Facility Name
University Orthopedics Center
City
State College
State/Province
Pennsylvania
ZIP/Postal Code
16801
Country
United States
Facility Name
Department of Orthopaedics, Brown University, Rhode Island Hospital
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02905
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
21967070
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.
Results Reference
derived
PubMed Identifier
19726771
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.
Results Reference
derived
Links:
URL
http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/125338lbl.pdf
Description
XIAFLEX Prescribing Information

Learn more about this trial

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

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