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

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ClinicalTrials.gov Identifier: NCT00528606
Recruitment Status : Completed
First Posted : September 12, 2007
Results First Posted : October 22, 2010
Last Update Posted : December 2, 2017
Sponsor:
Information provided by (Responsible Party):
Endo Pharmaceuticals

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Dupuytren's Contracture
Interventions Biological: collagenase clostridium histolyticum
Biological: Placebo
Enrollment 308
Recruitment Details  
Pre-assignment Details  
Arm/Group Title AA4500 0.58 mg Placebo
Hide Arm/Group Description collagenase clostridium histolyticum 0.58mg injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints Placebo injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints
Period Title: Overall Study
Started 204 104
Completed 191 100
Not Completed 13 4
Reason Not Completed
Withdrew consent             4             3
Lost to Follow-up             4             1
Adverse Event             3             0
Not specified             2             0
Arm/Group Title AA4500 0.58 mg Placebo Total
Hide Arm/Group Description collagenase clostridium histolyticum 0.58mg injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints placebo injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints Total of all reporting groups
Overall Number of Baseline Participants 204 104 308
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 204 participants 104 participants 308 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
120
  58.8%
57
  54.8%
177
  57.5%
>=65 years
84
  41.2%
47
  45.2%
131
  42.5%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 204 participants 104 participants 308 participants
62.3  (9.7) 63.3  (9.1) 62.7  (9.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 204 participants 104 participants 308 participants
Female
33
  16.2%
30
  28.8%
63
  20.5%
Male
171
  83.8%
74
  71.2%
245
  79.5%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 204 participants 104 participants 308 participants
White 203 104 307
Hispanic 1 0 1
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 204 participants 104 participants 308 participants
204 104 308
1.Primary Outcome
Title Clinical Success (Reduction in Contracture to 5° or Less) of the Primary Joint After the Last Injection
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Modified-Intent-to-Treat population (Intent-to-treat subjects were excluded from this population if they did not have fixed-flexion measurements after the first injection or had both screening and Treatment 1, Day 0 fixed-flexion measurements between 0 and 5 degrees)
Arm/Group Title AA4500 0.58 mg Placebo
Hide Arm/Group Description:
collagenase clostridium histolyticum 0.58mg injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints
placebo injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints
Overall Number of Participants Analyzed 203 103
Measure Type: Number
Unit of Measure: Percentage of Joints
64 6.8
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection AA4500 0.58 mg, Placebo
Comments p-value based on Cochran-Mantel-Haenszel test comparing treatment groups, stratified by baseline severity group and joint type.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
2.Secondary Outcome
Title Clinical Improvement After the Last Injection
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Modified ITT population( Intent-to-treat subjects were excluded from this population if they did not have fixed-flexion measurements after the first injection or had both screening and Treatment 1, Day 0 fixed-flexion measurements between 0 and 5 degrees)
Arm/Group Title AA4500 0.58 mg Placebo
Hide Arm/Group Description:
collagenase clostridium histolyticum 0.58mg injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints
placebo injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints
Overall Number of Participants Analyzed 203 103
Measure Type: Number
Unit of Measure: Percentage of Joints
84.7 11.7
3.Secondary Outcome
Title Percent Reduction From Baseline Contracture After the Last Injection
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Modified ITT population (Intent-to-treat subjects were excluded from this population if they did not have fixed-flexion measurements after the first injection or had both screening and Treatment 1, Day 0 fixed-flexion measurements between 0 and 5 degrees)
Arm/Group Title AA4500 0.58 mg Placebo
Hide Arm/Group Description:
collagenase clostridium histolyticum 0.58mg injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints
placebo injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints
Overall Number of Participants Analyzed 203 103
Mean (Standard Deviation)
Unit of Measure: Percent reduction from baseline
79.3  (32.58) 8.6  (30.78)
4.Secondary Outcome
Title Change From Baseline Range of Motion After the Last Injection
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Modified ITT Population (Intent-to-treat subjects were excluded from this population if they did not have fixed-flexion measurements after the first injection or had both screening and Treatment 1, Day 0 fixed-flexion measurements between 0 and 5 degrees)
Arm/Group Title AA4500 0.58 mg Placebo
Hide Arm/Group Description:
collagenase clostridium histolyticum 0.58mg injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints
placebo injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints
Overall Number of Participants Analyzed 198 103
Mean (Standard Deviation)
Unit of Measure: degrees
36.70  (21.01) 4.0  (14.77)
5.Secondary Outcome
Title Time to First Achieve Success After the Last Injection
Hide Description [Not Specified]
Time Frame Last evaluation visit on which clinical success is achieved through the Day 30 evaluation
Hide Outcome Measure Data
Hide Analysis Population Description
Modified ITT population
Arm/Group Title AA4500 0.58 mg Placebo
Hide Arm/Group Description:
collagenase clostridium histolyticum 0.58mg injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints
placebo injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints
Overall Number of Participants Analyzed 203 103
Measure Type: Number
Unit of Measure: percentage of joints
Injection 1, Day 1 12.8 0.0
Injection 1, Day 7 12.3 0.0
Injection 1, Day 30 14.3 1.0
Injection 2, Day 0 0.5 0.0
Injection 2, Day 1 4.9 0.0
Injection 2, Day 7 5.4 0.0
Injection 2, Day 30 6.4 1.0
Injection 3, Day 0 0.0 0.0
Injection 3, Day 1 2.0 0.0
Injection 3, Day 7 2.5 0.0
Injection 3, Day 30 2.5 4.9
Day 90 0.5 0.0
Did not reach clinical success by last injection 36.0 93.2
6.Secondary Outcome
Title Clinical Success (Reduction in Contracture to 5° or Less) After the First Injection
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Modified ITT population (Intent-to-treat subjects were excluded from this population if they did not have fixed-flexion measurements after the first injection or had both screening and Treatment 1, Day 0 fixed-flexion measurements between 0 and 5 degrees)
Arm/Group Title AA4500 0.58 mg Placebo
Hide Arm/Group Description:
collagenase clostridium histolyticum 0.58mg injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints
placebo injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints
Overall Number of Participants Analyzed 203 103
Measure Type: Number
Unit of Measure: Percentage of Joints
38.9 1.0
7.Secondary Outcome
Title Clinical Improvement After the First Injection
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Modified ITT population (Intent-to-treat subjects were excluded from this population if they did not have fixed-flexion measurements after the first injection or had both screening and Treatment 1, Day 0 fixed-flexion measurements between 0 and 5 degrees)
Arm/Group Title AA4500 0.58 mg Placebo
Hide Arm/Group Description:
collagenase clostridium histolyticum 0.58mg injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints
placebo injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints
Overall Number of Participants Analyzed 203 103
Measure Type: Number
Unit of Measure: Percentage of Joints
67.5 2.9
8.Secondary Outcome
Title Percent Reduction From Baseline Contracture After the First Injection
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Modified ITT population
Arm/Group Title AA4500 0.58 mg Placebo
Hide Arm/Group Description:
collagenase clostridium histolyticum 0.58mg injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints
placebo injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints
Overall Number of Participants Analyzed 203 103
Mean (Standard Deviation)
Unit of Measure: Percent reduction from baseline
64.8  (34.60) 4.7  (20.81)
9.Secondary Outcome
Title Change From Baseline Range of Motion After the First Injection
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Modified ITT population (Change in degree of motion measured as last available post-injection range of motion - baseline range of motion)
Arm/Group Title AA4500 0.58 mg Placebo
Hide Arm/Group Description:
collagenase clostridium histolyticum 0.58mg injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints
placebo injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints
Overall Number of Participants Analyzed 199 102
Mean (Standard Deviation)
Unit of Measure: degrees
28.30  (20.23) 1.50  (11.03)
Time Frame Non-serious adverse events (non-SAEs) were collected from time of study drug administration, serious adverse events (SAEs) were collected from time subject signed ICF. Non-SAEs & SAEs were collected until 30 days after completion or discharge from study.
Adverse Event Reporting Description This study was designed to be part of the larger clinical program. For information regarding XIAFLEX-associated Serious and Non-serious Adverse events please refer to the XIAFLEX Medication Guide & XIAFLEX Prescribing Information (see links above).
 
Arm/Group Title AA4500 0.58 mg Placebo
Hide Arm/Group Description collagenase clostridium histolyticum 0.58mg injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints placebo injected into metacarpophalangeal (MP) and/or proximal interphalangeal (PIP) joints
All-Cause Mortality
AA4500 0.58 mg Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
AA4500 0.58 mg Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   8/204 (3.92%)      1/104 (0.96%)    
Cardiac disorders     
Myocardial infarction * 1  1/204 (0.49%)  1 0/104 (0.00%)  0
Hepatobiliary disorders     
Acute cholecystitis * 1  0/204 (0.00%)  0 1/104 (0.96%)  1
Injury, poisoning and procedural complications     
Tendon rupture * 1  2/204 (0.98%)  2 0/104 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Ligament disorder * 1  1/204 (0.49%)  1 0/104 (0.00%)  0
Nervous system disorders     
Complex regional pain syndrome * 1  1/204 (0.49%)  1 0/104 (0.00%)  0
Psychiatric disorders     
Panic attack * 1  1/204 (0.49%)  1 0/104 (0.00%)  0
Renal and urinary disorders     
Pelvi-ureteric obstruction * 1  1/204 (0.49%)  1 0/104 (0.00%)  0
Surgical and medical procedures     
Spinal fusion surgery * 1  1/204 (0.49%)  1 0/104 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (8.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5.0%
AA4500 0.58 mg Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   196/204 (96.08%)      25/104 (24.04%)    
Blood and lymphatic system disorders     
Lymph node pain * 1  21/204 (10.29%)  25 0/104 (0.00%)  0
Lymphadenopathy * 1  20/204 (9.80%)  25 0/104 (0.00%)  0
General disorders     
Injection site haemorrhage * 1  76/204 (37.25%)  142 4/104 (3.85%)  4
Injection site pain * 1  66/204 (32.35%)  117 5/104 (4.81%)  7
Injection site pruritus * 1  11/204 (5.39%)  14 0/104 (0.00%)  0
Injection site swelling * 1  43/204 (21.08%)  63 4/104 (3.85%)  4
Oedema peripheral * 1  148/204 (72.55%)  296 4/104 (3.85%)  4
Tenderness * 1  54/204 (26.47%)  85 0/104 (0.00%)  0
Infections and infestations     
Nasopharyngitis * 1  7/204 (3.43%)  8 9/104 (8.65%)  9
Injury, poisoning and procedural complications     
Contusion * 1  104/204 (50.98%)  178 2/104 (1.92%)  2
Skin laceration * 1  22/204 (10.78%)  25 0/104 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Pain in extremity * 1  65/204 (31.86%)  95 3/104 (2.88%)  3
Skin and subcutaneous tissue disorders     
Blister * 1  11/204 (5.39%)  13 0/104 (0.00%)  0
Ecchymosis * 1  51/204 (25.00%)  72 1/104 (0.96%)  1
Erythema * 1  13/204 (6.37%)  16 0/104 (0.00%)  0
Pruritus * 1  22/204 (10.78%)  30 1/104 (0.96%)  2
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (8.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Auxilium Pharmaceuticals, Inc. agreements may vary with individual investigators but will not prohibit any investigator from publishing. Auxilium supports the publication of results from all centers of a multicenter trial but requests that reports based on single site data not preceed the primary publication of the entire clinical trial.
Results Point of Contact
Name/Title: Clinical Trial Coordinator
Organization: Endo Pharmaceuticals, Inc.
Responsible Party: Endo Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00528606     History of Changes
Other Study ID Numbers: AUX-CC-857
First Submitted: September 11, 2007
First Posted: September 12, 2007
Results First Submitted: September 24, 2010
Results First Posted: October 22, 2010
Last Update Posted: December 2, 2017