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EN3835 for the Treatment of Edematous Fibrosclerotic Panniculopathy (Commonly Known as Cellulite)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02724644
Recruitment Status : Completed
First Posted : March 31, 2016
Results First Posted : November 6, 2017
Last Update Posted : November 6, 2017
Sponsor:
Information provided by (Responsible Party):
Endo Pharmaceuticals

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Conditions Edematous Fibrosclerotic Panniculopathy
Cellulite
Interventions Biological: COLLAGENASE CLOSTRIDIUM HISTOLYTICUM
Biological: Placebo Comparator
Enrollment 375
Recruitment Details  
Pre-assignment Details  
Arm/Group Title EN3835 0.84 mg Placebo
Hide Arm/Group Description

Three (3) treatment sessions of 0.84 mg of collagenase clostridium histolyticum separated by approximately 21 days.

Injectable intervention

Three (3) treatment sessions of placebo separated by approximately 21 days. Injectable intervention
Period Title: Overall Study
Started 189 186
Completed 168 182
Not Completed 21 4
Reason Not Completed
Adverse Event             7             1
Lost to Follow-up             6             2
Withdrawal by Subject             7             1
Administrative             1             0
Arm/Group Title EN3835 0.84 mg Placebo Total
Hide Arm/Group Description

Three (3) treatment sessions of 0.84 mg of collagenase clostridium histolyticum separated by approximately 21 days.

Injectable intervention

Three (3) treatment sessions of placebo separated by approximately 21 days. Injectable intervention Total of all reporting groups
Overall Number of Baseline Participants 189 186 375
Hide Baseline Analysis Population Description
Analysis based on intent-to-treat (ITT) population; all randomized subjects who received at least 1 injection of study medication
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Participants
Number Analyzed 189 participants 186 participants 375 participants
47.2  (11.21) 45.8  (11.02) 46.5  (11.13)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 189 participants 186 participants 375 participants
18-<25 years
8
   4.2%
9
   4.8%
17
   4.5%
25-34 years
18
   9.5%
21
  11.3%
39
  10.4%
35-44 years
46
  24.3%
47
  25.3%
93
  24.8%
>=45 years
117
  61.9%
109
  58.6%
226
  60.3%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 189 participants 186 participants 375 participants
Female
189
 100.0%
186
 100.0%
375
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 189 participants 186 participants 375 participants
Hispanic or Latino
37
  19.6%
41
  22.0%
78
  20.8%
Not Hispanic or Latino
152
  80.4%
145
  78.0%
297
  79.2%
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 189 participants 186 participants 375 participants
American Indian or Alaska Native
1
   0.5%
1
   0.5%
2
   0.5%
Asian
3
   1.6%
1
   0.5%
4
   1.1%
Native Hawaiian or Other Pacific Islander
0
   0.0%
1
   0.5%
1
   0.3%
Black or African American
15
   7.9%
26
  14.0%
41
  10.9%
White
167
  88.4%
157
  84.4%
324
  86.4%
More than one race
3
   1.6%
0
   0.0%
3
   0.8%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 189 participants 186 participants 375 participants
189
 100.0%
186
 100.0%
375
 100.0%
1.Primary Outcome
Title Percentage of Composite Responders of at Least 2-Level Improvement of Severity
Hide Description Percentage of composite responders defined as subjects with an improvement from baseline of at least 2-levels of severity on each, the Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) and Patient-Reported Photonumeric Cellulite Severity Scale (PR-PCSS), at Day 71 in the ITT population. The CR-PCSS is a photonumeric scale that was used by the Investigator to evaluate cellulite ranging from 0 (none), 1 (almost none), 2 (mild), 3 (moderate), to 4 (severe). The PR-PCSS is a photonumeric scale that was used by the subjects to evaluate cellulite ranging from 0 (none), 1 (almost none), 2 (mild), 3 (moderate), to 4 (severe). A 2-level improvement on each scale for example would represent a change from a 4 (severe) to a 2 (mild). In order to be considered a responder a subject needs to have at least a 2-level improvement on both scales.
Time Frame Baseline, Day 71
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis is based on ITT population; all randomized subjects who received at least 1 injection of study medication
Arm/Group Title EN3835 0.84 mg Placebo
Hide Arm/Group Description:

Three (3) treatment sessions of 0.84 mg of collagenase clostridium histolyticum separated by approximately 21 days.

Injectable intervention

Three (3) treatment sessions of placebo separated by approximately 21 days. Injectable intervention
Overall Number of Participants Analyzed 189 186
Measure Type: Count of Participants
Unit of Measure: Participants
20
  10.6%
3
   1.6%
2.Secondary Outcome
Title Percentage of Composite Responders of at Least 1-Level Improvement of Severity
Hide Description Percentage of composite responders defined as subjects with improvement from baseline of at least 1-level of severity on each, the Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) and Patient-Reported Photonumeric Cellulite Severity Scale (PR-PCSS), at Day 71 in the ITT population. The CR-PCSS is a photonumeric scale that was used by the Investigator to evaluate cellulite ranging from 0 (none), 1 (almost none), 2 (mild), 3 (moderate), to 4 (severe). The PR-PCSS is a photonumeric scale that was used by the subjects to evaluate cellulite ranging from 0 (none), 1 (almost none), 2 (mild), 3 (moderate), to 4 (severe). A 1-level improvement on each scale for example would represent a change from a 4 (severe) to a 3 (moderate). In order to be considered a responder a subject needs to have at least a 1-level improvement on both scales.
Time Frame Baseline, Day 71
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis is based on ITT population; all randomized subjects who received at least 1 injection of study medication
Arm/Group Title EN3835 0.84 mg Placebo
Hide Arm/Group Description:

Three (3) treatment sessions of 0.84 mg of collagenase clostridium histolyticum separated by approximately 21 days.

Injectable intervention

Three (3) treatment sessions of placebo separated by approximately 21 days. Injectable intervention
Overall Number of Participants Analyzed 189 186
Measure Type: Count of Participants
Unit of Measure: Participants
79
  41.8%
33
  17.7%
3.Secondary Outcome
Title CR-PCSS Responder Analysis: 2-Levels of Severity
Hide Description Percentage of subjects with improvement from baseline of at least 2-levels of severity on the Investigator-rated Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) at Day 71.The CR-PCSS is a photonumeric scale that was used by the Investigator to evaluate cellulite ranging from 0 (none), 1 (almost none), 2 (mild), 3 (moderate), to 4 (severe). A 2-level improvement would be for example a change from 4 (severe) to 2 (mild).
Time Frame Baseline, Day 71
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis is based on modified intent-to-treat (mITT) population; all randomized subjects who received at least 1 injection of study medication and had at least 1 post-injection evaluation of both CR-PCSS by investigator and PR PCSS
Arm/Group Title EN3835 0.84 mg Placebo
Hide Arm/Group Description:

Three (3) treatment sessions of 0.84 mg of collagenase clostridium histolyticum separated by approximately 21 days.

Injectable intervention

Three (3) treatment sessions of placebo separated by approximately 21 days. Injectable intervention
Overall Number of Participants Analyzed 177 184
Measure Type: Count of Participants
Unit of Measure: Participants
32
  18.1%
9
   4.9%
4.Secondary Outcome
Title CR-PCSS Responder Analysis: 1-Level of Severity
Hide Description Percentage of subjects with improvement from baseline of at least 1-level of severity on the Investigator-rated Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) at Day 71.The CR-PCSS is a photonumeric scale that was used by the investigator to evaluate cellulite ranging from 0 (none), 1 (almost none), 2 (mild), 3 (moderate), to 4 (severe). A 1-level improvement would be for example a change from 4 (severe) to 3 (moderate).
Time Frame Baseline, Day 71
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis is based on modified intent-to-treat (mITT) population; all randomized subjects who received at least 1 injection of study medication and had at least 1 post-injection evaluation of both CR-PCSS by investigator and PR PCSS
Arm/Group Title EN3835 0.84 mg Placebo
Hide Arm/Group Description:

Three (3) treatment sessions of 0.84 mg of collagenase clostridium histolyticum separated by approximately 21 days.

Injectable intervention

Three (3) treatment sessions of placebo separated by approximately 21 days. Injectable intervention
Overall Number of Participants Analyzed 177 184
Measure Type: Count of Participants
Unit of Measure: Participants
96
  54.2%
53
  28.8%
5.Secondary Outcome
Title CR-PCSS Change From Baseline
Hide Description The CR-PCSS is a photonumeric scale that was used by the investigator to evaluate cellulite ranging from 0 (none), 1 (almost none), 2 (mild), 3 (moderate), to 4 (severe). Change is Day 71 study visit rating minus baseline visit; negative values indicate a lessening in cellulite severity.
Time Frame Baseline, Day 71
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis is based on mITT population; all randomized subjects who received at least 1 injection of study medication and had at least 1 post-injection evaluation of both CR-PCSS by investigator and PR PCSS
Arm/Group Title EN3835 0.84 mg Placebo
Hide Arm/Group Description:

Three (3) treatment sessions of 0.84 mg of collagenase clostridium histolyticum separated by approximately 21 days.

Injectable intervention

Three (3) treatment sessions of placebo separated by approximately 21 days. Injectable intervention
Overall Number of Participants Analyzed 177 184
Mean (Standard Deviation)
Unit of Measure: units on a scale
-0.7  (0.83) -0.3  (0.62)
6.Secondary Outcome
Title PR-PCSS Responder Analysis: 2-Levels of Severity
Hide Description Percentage of subjects with improvement from baseline of at least 2-levels of severity on the subject-rated Patient-Reported Photonumeric Cellulite Severity Scale (PR-PCSS) at Day 71.The PR-PCSS is a photonumeric scale that was used by the subject to evaluate cellulite ranging from 0 (none), 1 (almost none), 2 (mild), 3 (moderate), to 4 (severe). A 2-level improvement would be for example a change from 4 (severe) to 2 (mild).
Time Frame Baseline, Day 71
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis is based on mITT population; all randomized subjects who received at least 1 injection of study medication and had at least 1 post-injection evaluation of both CR-PCSS by investigator and PR PCSS
Arm/Group Title EN3835 0.84 mg Placebo
Hide Arm/Group Description:

Three (3) treatment sessions of 0.84 mg of collagenase clostridium histolyticum separated by approximately 21 days.

Injectable intervention

Three (3) treatment sessions of placebo separated by approximately 21 days. Injectable intervention
Overall Number of Participants Analyzed 177 184
Measure Type: Count of Participants
Unit of Measure: Participants
51
  28.8%
24
  13.0%
7.Secondary Outcome
Title PR-PCSS Responder Analysis: 1-Level of Severity
Hide Description Percentage of subjects with improvement from baseline of at least 1-level of severity on the subject-rated Patient-Reported Photonumeric Cellulite Severity Scale (PR-PCSS) at Day 71.The PR-PCSS is a photonumeric scale that was used by the subject to evaluate cellulite ranging from 0 (none), 1 (almost none), 2 (mild), 3 (moderate), to 4 (severe). A 1-level improvement would be for example a change from 4 (severe) to 3 (moderate).
Time Frame Baseline, Day 71
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis is based on mITT population; all randomized subjects who received at least 1 injection of study medication and had at least 1 post-injection evaluation of both CR-PCSS by investigator and PR PCSS
Arm/Group Title EN3835 0.84 mg Placebo
Hide Arm/Group Description:

Three (3) treatment sessions of 0.84 mg of collagenase clostridium histolyticum separated by approximately 21 days.

Injectable intervention

Three (3) treatment sessions of placebo separated by approximately 21 days. Injectable intervention
Overall Number of Participants Analyzed 177 184
Measure Type: Count of Participants
Unit of Measure: Participants
128
  72.3%
95
  51.6%
8.Secondary Outcome
Title PR-PCSS Change From Baseline
Hide Description The PR-PCSS is a photonumeric scale that was used by the subjects to evaluate cellulite ranging from 0 (none), 1 (almost none), 2 (mild), 3 (moderate), to 4 (severe). Change is Day 71 study visit rating minus baseline visit; negative values indicate a lessening in cellulite severity.
Time Frame Baseline, Day 71
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis is based on mITT population; all randomized subjects who received at least 1 injection of study medication and had at least 1 post-injection evaluation of both CR-PCSS by investigator and PR PCSS
Arm/Group Title EN3835 0.84 mg Placebo
Hide Arm/Group Description:

Three (3) treatment sessions of 0.84 mg of collagenase clostridium histolyticum separated by approximately 21 days.

Injectable intervention

Three (3) treatment sessions of placebo separated by approximately 21 days. Injectable intervention
Overall Number of Participants Analyzed 177 184
Mean (Standard Deviation)
Unit of Measure: units on a scale
-1.0  (0.89) -0.7  (0.79)
9.Secondary Outcome
Title Investigator Assessment of Improvement Based on the Investigator Global Aesthetic Improvement Scale (I-GAIS)
Hide Description On Day 71, the Investigator determined the degree of improvement from baseline in the treated area using the 7-point I-GAIS. Ratings could be improved (+1), much improved (+2), or very much improved (+3), or no change (0), or worse (-1), much worse (-2) or very much worse (-3).
Time Frame Day 71
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis is based on mITT population; all randomized subjects who received at least 1 injection of study medication and had at least 1 post-injection evaluation of both CR-PCSS by investigator and PR PCSS
Arm/Group Title EN3835 0.84 mg Placebo
Hide Arm/Group Description:

Three (3) treatment sessions of 0.84 mg of collagenase clostridium histolyticum separated by approximately 21 days.

Injectable intervention

Three (3) treatment sessions of placebo separated by approximately 21 days. Injectable intervention
Overall Number of Participants Analyzed 177 184
Measure Type: Count of Participants
Unit of Measure: Participants
Very Much Improved (3) 6 2
Much improved (2) 40 15
Improved (1) 64 43
No Change( 0) 57 119
Worse (-1) 6 4
Much worse (-2) 2 0
Very Much Worse (-3) 0 0
Not done 2 1
10.Secondary Outcome
Title Subject Assessment of Improvement Based on the Subject Global Aesthetic Improvement Scale (S-GAIS)
Hide Description At Day 71, subjects were asked to rate their opinion of the overall improvement of their treated area using the 7-point S-GAIS. Ratings could be improved (+1), much improved (+2), or very much improved (+3), or no change (0), or worse (-1), much worse (-2) or very much worse (-3)
Time Frame Day 71
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis is based on mITT population; all randomized subjects who received at least 1 injection of study medication and had at least 1 post-injection evaluation of both CR-PCSS by investigator and PR PCSS
Arm/Group Title EN3835 0.84 mg Placebo
Hide Arm/Group Description:

Three (3) treatment sessions of 0.84 mg of collagenase clostridium histolyticum separated by approximately 21 days.

Injectable intervention

Three (3) treatment sessions of placebo separated by approximately 21 days. Injectable intervention
Overall Number of Participants Analyzed 177 184
Measure Type: Count of Participants
Unit of Measure: Participants
Very Much Improved (3) 21 11
Much Improved (2) 43 17
Improved (1) 64 52
No change (0) 38 97
Worse (-1) 6 5
Much Worse (-2) 3 0
Very Much Worse (-3) 0 0
Not done 2 2
11.Secondary Outcome
Title Subject Satisfaction Assessment Based on the the Subject Satisfaction Scale
Hide Description At Day 71, subjects were asked to rate their satisfaction with cellulite treatment using the 5-point subject satisfaction scale. Ratings could be satisfied (+1), very satisfied (+2), neither satisfied nor dissatisfied (0), or dissatisfied (-1), very dissatisfied (-2).
Time Frame Day 71
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis is based on mITT population; all randomized subjects who received at least 1 injection of study medication and had at least 1 post-injection evaluation of both CR-PCSS by investigator and PR PCSS
Arm/Group Title EN3835 0.84 mg Placebo
Hide Arm/Group Description:

Three (3) treatment sessions of 0.84 mg of collagenase clostridium histolyticum separated by approximately 21 days.

Injectable intervention

Three (3) treatment sessions of placebo separated by approximately 21 days. Injectable intervention
Overall Number of Participants Analyzed 177 184
Measure Type: Count of Participants
Unit of Measure: Participants
Very Satisfied (2) 41 25
Satisfied (1) 69 40
Neither Satisfied nor Dissatisfied (0) 45 82
Dissatisfied (-1) 11 18
Very Dissatisfied (-2) 9 16
Not done 2 3
12.Secondary Outcome
Title Change in the Hexsel Cellulite Severity Scale (CSS) Total Score
Hide Description Investigator used the Hexsel CSS to assess the severity of cellulite. The total score could range from 0 (no cellulite) to 15 (extremely severe cellulite). Negative change in Hexsel CSS total score indicates an improvement in cellulite severity
Time Frame Baseline, Day 71
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis is based on mITT population; all randomized subjects who received at least 1 injection of study medication and had at least 1 post-injection evaluation of both CR-PCSS by investigator and PR PCSS
Arm/Group Title EN3835 0.84 mg Placebo
Hide Arm/Group Description:

Three (3) treatment sessions of 0.84 mg of collagenase clostridium histolyticum separated by approximately 21 days.

Injectable intervention

Three (3) treatment sessions of placebo separated by approximately 21 days. Injectable intervention
Overall Number of Participants Analyzed 177 184
Mean (Standard Deviation)
Unit of Measure: units on a scale
-1.7  (2.20) -0.9  (2.00)
Time Frame Baseline, Day 71
Adverse Event Reporting Description Serious Adverse Events by Frequency (Safety Population)
 
Arm/Group Title EN3835 0.84 mg Placebo
Hide Arm/Group Description

Three (3) treatment sessions of 0.84 mg of collagenase clostridium histolyticum separated by approximately 21 days.

Injectable intervention

Three (3) treatment sessions of placebo separated by approximately 21 days. Injectable intervention
All-Cause Mortality
EN3835 0.84 mg Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
EN3835 0.84 mg Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/189 (0.53%)      0/186 (0.00%)    
Pregnancy, puerperium and perinatal conditions     
Abortion spontaneous * 1 [1]  1/189 (0.53%)  1 0/186 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (19.0)
[1]
Serious Adverse Events by Frequency (Safety Population)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
EN3835 0.84 mg Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   148/189 (78.31%)      30/186 (16.13%)    
General disorders     
Injection site bruising  1 [1]  142/189 (75.13%)  314 25/186 (13.44%)  33
Injection site pain  1 [1]  112/189 (59.26%)  228 10/186 (5.38%)  11
Injection site nodule  1 [1]  27/189 (14.29%)  33 0/186 (0.00%)  0
Injection site pruritus  1 [1]  21/189 (11.11%)  29 1/186 (0.54%)  1
Injection site induration  1 [1]  11/189 (5.82%)  17 0/186 (0.00%)  0
Injection site swelling  1 [1]  14/189 (7.41%)  17 1/186 (0.54%)  2
Injection site mass  1 [1]  10/189 (5.29%)  12 1/186 (0.54%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (19.0)
[1]
Administration site conditions
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.inquires@endo.com
Layout table for additonal information
Responsible Party: Endo Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02724644     History of Changes
Other Study ID Numbers: EN3835-201
First Submitted: March 10, 2016
First Posted: March 31, 2016
Results First Submitted: August 28, 2017
Results First Posted: November 6, 2017
Last Update Posted: November 6, 2017