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Clinical Study for the Treatment of Adhesive Capsulitis of the Shoulder (AC)

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ClinicalTrials.gov Identifier: NCT02006719
Recruitment Status : Completed
First Posted : December 10, 2013
Results First Posted : May 25, 2017
Last Update Posted : October 5, 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
Conditions Adhesive Capsulitis
Frozen Shoulder
Interventions Biological: Collagenase Clostridium Histolyticum
Other: Placebo
Enrollment 322
Recruitment Details  
Pre-assignment Details  
Arm/Group Title AA4500 Placebo
Hide Arm/Group Description Up to 3 injections of 0.58 mg/1 mL collagenase clostridium histolyticum (AA4500), minimum of 21 days apart and home shoulder exercise Up to three 1-mL injections of placebo, minimum of 21 days apart and home shoulder exercise
Period Title: Overall Study
Started 237 85
Completed 219 80
Not Completed 18 5
Reason Not Completed
Withdrawal by Subject             10             2
Lost to Follow-up             5             1
Protocol Violation             2             0
Adverse Event             1             1
Other/Unknown             0             1
Arm/Group Title AA4500 Placebo Total
Hide Arm/Group Description Up to 3 injections of 0.58 mg/1 mL AA4500, minimum of 21 days apart and home shoulder exercise Up to three 1-mL injections of placebo, minimum of 21 days apart and home shoulder exercise Total of all reporting groups
Overall Number of Baseline Participants 237 84 321
Hide Baseline Analysis Population Description
All participants who received at least 1 administration of study drug (1 participant excluded)
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 237 participants 84 participants 321 participants
53.0
(29 to 75)
51.0
(22 to 70)
52.0
(22 to 75)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 237 participants 84 participants 321 participants
<45
30
  12.7%
14
  16.7%
44
  13.7%
45-54
114
  48.1%
44
  52.4%
158
  49.2%
55-64
75
  31.6%
23
  27.4%
98
  30.5%
65-74
17
   7.2%
3
   3.6%
20
   6.2%
≥75
1
   0.4%
0
   0.0%
1
   0.3%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 237 participants 84 participants 321 participants
Female
162
  68.4%
60
  71.4%
222
  69.2%
Male
75
  31.6%
24
  28.6%
99
  30.8%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 237 participants 84 participants 321 participants
Hispanic or Latino
17
   7.2%
4
   4.8%
21
   6.5%
Not Hispanic or Latino
220
  92.8%
80
  95.2%
300
  93.5%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 237 participants 84 participants 321 participants
American Indian or Alaska Native
0
   0.0%
1
   1.2%
1
   0.3%
Asian
6
   2.5%
4
   4.8%
10
   3.1%
Native Hawaiian or Other Pacific Islander
2
   0.8%
0
   0.0%
2
   0.6%
Black or African American
22
   9.3%
7
   8.3%
29
   9.0%
White
205
  86.5%
72
  85.7%
277
  86.3%
More than one race
1
   0.4%
0
   0.0%
1
   0.3%
Unknown or Not Reported
1
   0.4%
0
   0.0%
1
   0.3%
1.Primary Outcome
Title Change From Baseline to Day 95 in Active Forward Flexion
Hide Description Active range of motion (AROM) measurement using a goniometer to assess forward flexion in the affected shoulder
Time Frame Baseline, day 95
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who have a baseline AROM measurement of the affected shoulder and at least 1 measurement of AROM of the affected shoulder following the first administration of study drug (1 participant excluded); 25 participants missing either baseline or day 95 active forward flexion measurement also excluded
Arm/Group Title AA4500 Placebo
Hide Arm/Group Description:
Up to 3 injections of 0.58 mg/1 mL AA4500, minimum of 21 days apart and home shoulder exercise
Up to three 1-mL injections of placebo, minimum of 21 days apart and home shoulder exercise
Overall Number of Participants Analyzed 217 79
Mean (Standard Deviation)
Unit of Measure: degrees
41.0  (28.89) 35.9  (23.36)
2.Secondary Outcome
Title Change From Baseline to Day 95 in Adapted American Shoulder and Elbow Surgeons (ASES) Function Subscale
Hide Description Function subscale score ranging from 0-50, with 0 being most dysfunctional, derived from participant assessment of ability to do 10 activities with affected shoulder/arm where 0=unable to do to, 1=very difficult to do, 2=somewhat difficult, and 3=not difficult, and calculated as (cumulative total score for the 10 activity items) × (5/3); adapted from ASES Standardized Shoulder Assessment Form, Patient Self-Evaluation (United States adapted version).
Time Frame Baseline, day 95
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who have a baseline AROM measurement of the affected shoulder and at least 1 measurement of AROM of the affected shoulder following the first administration of study drug (1 participant excluded); 34 participants missing either baseline or day 95 function subscale scores also excluded
Arm/Group Title AA4500 Placebo
Hide Arm/Group Description:
Up to 3 injections of 0.58 mg/1 mL AA4500, minimum of 21 days apart and home shoulder exercise
Up to three 1-mL injections of placebo, minimum of 21 days apart and home shoulder exercise
Overall Number of Participants Analyzed 211 76
Mean (Standard Deviation)
Unit of Measure: units on a scale
17.0  (11.65) 14.8  (11.14)
3.Secondary Outcome
Title Change From Baseline to Day 95 in Pain With Movement Using 11-point Numeric Rating Scale (NRS)
Hide Description Participant assessment of pain in response to "How bad is the pain upon movement of your affected shoulder at its worst in the last 24 hours?" using an 11-point NRS where 0=no pain at all and 10=pain as bad as it can be.
Time Frame Baseline, day 95
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who have a baseline AROM measurement of the affected shoulder and at least 1 measurement of AROM of the affected shoulder following the first administration of study drug (1 participant excluded); 33 participants missing either baseline or day 95 pain with movement scores also excluded
Arm/Group Title AA4500 Placebo
Hide Arm/Group Description:
Up to 3 injections of 0.58 mg/1 mL AA4500, minimum of 21 days apart and home shoulder exercise
Up to three 1-mL injections of placebo, minimum of 21 days apart and home shoulder exercise
Overall Number of Participants Analyzed 211 77
Mean (Standard Deviation)
Unit of Measure: units on a scale
-4.4  (2.83) -3.9  (2.93)
4.Secondary Outcome
Title Change From Baseline to Day 95 in Active Abduction
Hide Description AROM measurement using a goniometer to assess abduction in the affected shoulder
Time Frame Baseline, day 95
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who have a baseline AROM measurement of the affected shoulder and at least 1 measurement of AROM of the affected shoulder following the first administration of study drug (1 participant excluded); 25 participants missing either baseline or day 95 active abduction measurement also excluded
Arm/Group Title AA4500 Placebo
Hide Arm/Group Description:
Up to 3 injections of 0.58 mg/1 mL AA4500, minimum of 21 days apart and home shoulder exercise
Up to three 1-mL injections of placebo, minimum of 21 days apart and home shoulder exercise
Overall Number of Participants Analyzed 217 79
Mean (Standard Deviation)
Unit of Measure: degrees
49.0  (33.10) 43.8  (30.71)
5.Secondary Outcome
Title Change From Baseline to Day 95 in Passive Forward Flexion
Hide Description Passive range of motion (PROM) measurement using a goniometer to assess forward flexion in the affected shoulder
Time Frame Baseline, day 95
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who have a baseline AROM measurement of the affected shoulder and at least 1 measurement of AROM of the affected shoulder following the first administration of study drug (1 participant excluded); 25 participants missing either baseline or day 95 active forward flexion measurement also excluded
Arm/Group Title AA4500 Placebo
Hide Arm/Group Description:
Up to 3 injections of 0.58 mg/1 mL AA4500, minimum of 21 days apart and home shoulder exercise
Up to three 1-mL injections of placebo, minimum of 21 days apart and home shoulder exercise
Overall Number of Participants Analyzed 217 79
Mean (Standard Deviation)
Unit of Measure: degrees
39.3  (29.47) 34.1  (22.37)
6.Secondary Outcome
Title Change From Baseline to Day 95 in Passive Abduction
Hide Description PROM measurement using a goniometer to assess abduction in the affected shoulder
Time Frame Baseline, day 95
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who have a baseline AROM measurement of the affected shoulder and at least 1 measurement of AROM of the affected shoulder following the first administration of study drug (1 participant excluded); 25 participants missing either baseline or day 95 passive abduction measurement also excluded
Arm/Group Title AA4500 Placebo
Hide Arm/Group Description:
Up to 3 injections of 0.58 mg/1 mL AA4500, minimum of 21 days apart and home shoulder exercise
Up to three 1-mL injections of placebo, minimum of 21 days apart and home shoulder exercise
Overall Number of Participants Analyzed 217 79
Mean (Standard Deviation)
Unit of Measure: degrees
45.4  (33.69) 42.8  (32.12)
7.Secondary Outcome
Title Change From Baseline to Day 95 in Active Internal Rotation
Hide Description AROM measurement using a goniometer to assess internal rotation in the affected shoulder
Time Frame Baseline, day 95
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who have a baseline AROM measurement of the affected shoulder and at least 1 measurement of AROM of the affected shoulder following the first administration of study drug (1 participant excluded); 25 participants missing either baseline or day 95 active internal rotation measurement also excluded
Arm/Group Title AA4500 Placebo
Hide Arm/Group Description:
Up to 3 injections of 0.58 mg/1 mL AA4500, minimum of 21 days apart and home shoulder exercise
Up to three 1-mL injections of placebo, minimum of 21 days apart and home shoulder exercise
Overall Number of Participants Analyzed 217 79
Mean (Standard Deviation)
Unit of Measure: degrees
23.1  (25.21) 20.9  (23.58)
8.Secondary Outcome
Title Change From Baseline to Day 95 in Active External Rotation
Hide Description AROM measurement using a goniometer to assess external rotation in the affected shoulder
Time Frame Baseline, day 95
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who have a baseline AROM measurement of the affected shoulder and at least 1 measurement of AROM of the affected shoulder following the first administration of study drug (1 participant excluded); 25 participants missing either baseline or day 95 active external rotation measurement also excluded
Arm/Group Title AA4500 Placebo
Hide Arm/Group Description:
Up to 3 injections of 0.58 mg/1 mL AA4500, minimum of 21 days apart and home shoulder exercise
Up to three 1-mL injections of placebo, minimum of 21 days apart and home shoulder exercise
Overall Number of Participants Analyzed 217 79
Mean (Standard Deviation)
Unit of Measure: degrees
28.6  (21.30) 26.1  (22.67)
9.Secondary Outcome
Title Change From Baseline to Day 95 in Passive Internal Rotation
Hide Description PROM measurement using a goniometer to assess internal rotation in the affected shoulder
Time Frame Baseline, day 95
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who have a baseline AROM measurement of the affected shoulder and at least 1 measurement of AROM of the affected shoulder following the first administration of study drug (1 participant excluded); 25 participants missing either baseline or day 95 passive internal rotation measurement also excluded
Arm/Group Title AA4500 Placebo
Hide Arm/Group Description:
Up to 3 injections of 0.58 mg/1 mL AA4500, minimum of 21 days apart and home shoulder exercise
Up to three 1-mL injections of placebo, minimum of 21 days apart and home shoulder exercise
Overall Number of Participants Analyzed 217 79
Mean (Standard Deviation)
Unit of Measure: degrees
24.1  (23.77) 20.3  (23.61)
10.Secondary Outcome
Title Change From Baseline to Day 95 in Passive External Rotation
Hide Description PROM measurement using a goniometer to assess external rotation in the affected shoulder
Time Frame Baseline, day 95
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who have a baseline AROM measurement of the affected shoulder and at least 1 measurement of AROM of the affected shoulder following the first administration of study drug (1 participant excluded); 25 participants missing either baseline or day 95 passive external rotation measurement also excluded
Arm/Group Title AA4500 Placebo
Hide Arm/Group Description:
Up to 3 injections of 0.58 mg/1 mL AA4500, minimum of 21 days apart and home shoulder exercise
Up to three 1-mL injections of placebo, minimum of 21 days apart and home shoulder exercise
Overall Number of Participants Analyzed 217 79
Mean (Standard Deviation)
Unit of Measure: degrees
24.8  (22.31) 24.4  (26.16)
11.Secondary Outcome
Title Change From Baseline to Day 95 in Adapted ASES Pain Subscale
Hide Description Pain subscale score ranging from 0-50, with 0 being greatest pain, derived from participant overall assessment of pain in response to "How bad is the pain in your affected shoulder today?" using an 11-point NRS where 0=no pain at all and 10=pain as bad as it can be and calculated as (10 - NRS score) x 5; adapted from ASES Standardized Shoulder Assessment Form, Patient Self-Evaluation
Time Frame Baseline, day 95
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who have a baseline AROM measurement of the affected shoulder and at least 1 measurement of AROM of the affected shoulder following the first administration of study drug (1 participant excluded); 33 participants missing either baseline or day 95 pain subscale scores also excluded
Arm/Group Title AA4500 Placebo
Hide Arm/Group Description:
Up to 3 injections of 0.58 mg/1 mL AA4500, minimum of 21 days apart and home shoulder exercise
Up to three 1-mL injections of placebo, minimum of 21 days apart and home shoulder exercise
Overall Number of Participants Analyzed 211 77
Mean (Standard Deviation)
Unit of Measure: units on a scale
15.9  (13.46) 13.5  (13.45)
12.Secondary Outcome
Title Subject Satisfaction With Treatment at Day 95
Hide Description Participant assessment of satisfaction with treatment rated as very satisfied, quite satisfied, neither satisfied nor dissatisfied, quite dissatisfied, or very dissatisfied.
Time Frame Day 95
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who have a baseline AROM measurement of the affected shoulder and at least 1 measurement of AROM of the affected shoulder following the first administration of study drug (1 participant excluded); 11 participants not completing questionnaire also excluded
Arm/Group Title AA4500 Placebo
Hide Arm/Group Description:
Up to 3 injections of 0.58 mg/1 mL AA4500, minimum of 21 days apart and home shoulder exercise
Up to three 1-mL injections of placebo, minimum of 21 days apart and home shoulder exercise
Overall Number of Participants Analyzed 229 81
Measure Type: Number
Unit of Measure: participants
Very satisfied 142 43
Quite satisfied 38 22
Neither satisfied nor dissatisfied 32 8
Quite dissatisfied 10 2
Very dissatisfied 7 6
13.Secondary Outcome
Title Investigator Assessment of Improvement With Treatment at Day 95
Hide Description Investigator assessment of degree of improvement in severity of the participant's treated shoulder compared with screening rated as very much improved, much improved, minimally improved, no change, minimally worse, much worse, or very much worse.
Time Frame Day 95
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who have a baseline AROM measurement of the affected shoulder and at least 1 measurement of AROM of the affected shoulder following the first administration of study drug (1 participant excluded); 10 participants also excluded for incomplete questionnaire
Arm/Group Title AA4500 Placebo
Hide Arm/Group Description:
Up to 3 injections of 0.58 mg/1 mL AA4500, minimum of 21 days apart and home shoulder exercise
Up to three 1-mL injections of placebo, minimum of 21 days apart and home shoulder exercise
Overall Number of Participants Analyzed 229 82
Measure Type: Number
Unit of Measure: participants
Very much improved 94 27
Much improved 73 31
Minimally improved 41 16
No change 13 8
Minimally worse 6 0
Much worse 1 0
Very much worse 1 0
Time Frame 130 days (up to 28 day screening period and 95±7 day study period)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title AA4500 Placebo
Hide Arm/Group Description Up to 3 injections of 0.58 mg/1 mL AA4500, minimum of 21 days apart and home shoulder exercise Up to three 1-mL injections of placebo, minimum of 21 days apart and home shoulder exercise
All-Cause Mortality
AA4500 Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
AA4500 Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/237 (1.69%)      1/84 (1.19%)    
Cardiac disorders     
Atrial fibrilation * 1  1/237 (0.42%)  1 0/84 (0.00%)  0
Gastrointestinal disorders     
Gastric ulcer * 1  0/237 (0.00%)  0 1/84 (1.19%)  1
Injury, poisoning and procedural complications     
Overdose * 1  1/237 (0.42%)  1 0/84 (0.00%)  0
Post procedural bile leak * 1  1/237 (0.42%)  1 0/84 (0.00%)  0
Procedural pain * 1  1/237 (0.42%)  1 0/84 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Glioblastoma * 1  1/237 (0.42%)  1 0/84 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (16.1)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
AA4500 Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   188/237 (79.32%)      37/84 (44.05%)    
General disorders     
Injection site bruising * 1  52/237 (21.94%)  65 10/84 (11.90%)  13
Injection site pain * 1  50/237 (21.10%)  77 11/84 (13.10%)  17
Localised oedema * 1  20/237 (8.44%)  28 1/84 (1.19%)  1
Injury, poisoning and procedural complications     
Contusion * 1  71/237 (29.96%)  106 2/84 (2.38%)  2
Musculoskeletal and connective tissue disorders     
Musculoskeletal pain * 1  90/237 (37.97%)  138 18/84 (21.43%)  24
Pain in extremity * 1  13/237 (5.49%)  16 4/84 (4.76%)  5
Skin and subcutaneous tissue disorders     
Ecchymosis * 1  47/237 (19.83%)  69 3/84 (3.57%)  4
Pruritus * 1  12/237 (5.06%)  15 0/84 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (16.1)
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Clinical Trial Coordinator
Organization: Endo Pharmaceuticals Inc.
EMail: clinicalsite.inquiries@endo.com
Layout table for additonal information
Responsible Party: Endo Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02006719     History of Changes
Other Study ID Numbers: AUX-CC-871
First Submitted: December 2, 2013
First Posted: December 10, 2013
Results First Submitted: April 18, 2017
Results First Posted: May 25, 2017
Last Update Posted: October 5, 2017