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A Phase 2a Study to Evaluate the Safety and Efficacy of AZX100 in Trocar Sites of Arthroscopic Shoulder Surgery Patients

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: NCT00811577
Recruitment Status : Completed
First Posted : December 19, 2008
Results First Posted : October 11, 2012
Last Update Posted : October 11, 2012
Sponsor:
Information provided by (Responsible Party):
Capstone Therapeutics

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Prevention
Conditions Scar Prevention
Scar Reduction
Interventions Drug: Placebo
Drug: AZX100
Enrollment 150
Recruitment Details Enrollment in the study began in January 2009 and was completed in December 2009. All patients were enrolled in dermatological medical clinics.
Pre-assignment Details  
Arm/Group Title AZX100-Placebo Arm Placebo-only Arm
Hide Arm/Group Description Three trocar sites designated as anterior, lateral and posterior will be randomized on each patient to receive one low dose of AZX100, one high dose of AZX100, or placebo. Three trocar sites on each patient will receive one dose of placebo.
Period Title: Overall Study
Started 126 24
Completed 116 23
Not Completed 10 1
Reason Not Completed
Lost to Follow-up             7             1
Withdrawal by Subject             3             0
Arm/Group Title AZX100-Placebo Arm Placebo-only Arm Total
Hide Arm/Group Description Three trocar sites designated as anterior, lateral and posterior will be randomized on each patient to receive one low dose of AZX100, one high dose of AZX100, or placebo. Three trocar sites on each patient will receive one dose of placebo. Total of all reporting groups
Overall Number of Baseline Participants 126 24 150
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 126 participants 24 participants 150 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
112
  88.9%
19
  79.2%
131
  87.3%
>=65 years
14
  11.1%
5
  20.8%
19
  12.7%
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 126 participants 24 participants 150 participants
51.3  (11.8) 51.8  (13.2) 51.4  (12.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 126 participants 24 participants 150 participants
Female
36
  28.6%
7
  29.2%
43
  28.7%
Male
90
  71.4%
17
  70.8%
107
  71.3%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 126 participants 24 participants 150 participants
126 24 150
1.Primary Outcome
Title Differences Among the 3 Dosage Groups in the Patient (PSAS) and Observer (OSAS) Scar Assessment Scale (POSAS) Scores
Hide Description Efficacy was based on the difference between mean POSAS scores of placebo and 3 mg AZX100, and placebo and 10 mg AZX100 12 months after shoulder surgery. Three trocar sites were randomized on each patient to receive AZX100 3 mg or AZX100 10 mg or placebo at 9 days and 21 days after shoulder surgery. PSAS results included patients' ratings on a scale of 1-10 (1 was normal skin or no complaints and 10 was the worst imaginable scar or the worst difference) for the following: Is the scar painful? Is the scar itching? Is the color of the scar different? Is the scar more stiff? Is the thickness of the scar different? Is the scar irregular? The possible minimum score was 6 and the maximum (worst) score was 60. OSAS results included observers' ratings on a scale of 1-10 (1 was normal skin and 10 was the worst scar imaginable) for vascularization, pigmentation, thickness, relief, and pliability. The possible minimum score was 5 and the possible maximum (worst) score was 50.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
The efficacy analysis was based on patient data from the AZX100/Placebo cohort (i.e., not including the patients receiving placebo-only). In the ITT sample for the POSAS outcomes, available sample sizes were 122 at Day 42 and 113 at Month 12 (including 4 subjects who withdrew from the study but were still followed for safety until Month 12).
Arm/Group Title PSAS Results for Placebo Trocar Scars PSAS Results for 3 mg AZX100 Trocar Scars PSAS Results for 10 mg AZX100 Trocar Scars OSAS Results for Placebo Trocar Scars OSAS Results for 3 mg AZX100 Trocar Scars OSAS Results for 10 mg AZX100 Trocar Scars
Hide Arm/Group Description:
This group included PSAS results at 12 months for trocar scars that were randomized to receive saline placebo/cm at 9 days and 21 days following shoulder surgery.
This group included PSAS results at 12 months for trocar scars that were randomized to receive AZX100 3 mg/cm at 9 days and 21 days following shoulder surgery.
This group included PSAS results at 12 months for trocar scars that were randomized to receive AZX100 10 mg/cm at 9 days and 21 days following shoulder surgery.
This group included OSAS results at 12 months for trocar scars that were randomized to receive saline placebo/cm at 9 days and 21 days following shoulder surgery.
This group included OSAS results at 12 months for trocar scars that were randomized to receive AZX100 3 mg/cm at 9 days and 21 days following shoulder surgery.
This group included OSAS results at 12 months for trocar scars that were randomized to receive AZX100 10 mg/cm at 9 days and 21 days following shoulder surgery.
Overall Number of Participants Analyzed 113 113 113 113 113 113
Mean (Standard Deviation)
Unit of Measure: Units on a scale
8.0  (4.1) 8.0  (4.7) 8.3  (5.0) 6.8  (2.7) 6.8  (2.5) 6.9  (2.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PSAS Results for Placebo Trocar Scars, PSAS Results for 3 mg AZX100 Trocar Scars
Comments Using serial gate-keeping to preserve the 5% overall type I error of 1-4 two-sided tests, 2-sided Wilcoxon Signed Rank tests were used. Computer graphics were used to display outcomes at Month 12, compare paired differences of outcomes between the 2 dosages and placebo, and show time trends in mean outcomes. Repeated measures regression models (GEE models in SAS/STAT PROC GENMOD) were used to examine longitudinal outcomes with terms for treatment and trocar location adjusted for key covariates.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.57
Comments For this early phase study, multiple comparisons adjustments were not used.
Method Wilcoxon (signed rank)
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection PSAS Results for Placebo Trocar Scars, PSAS Results for 10 mg AZX100 Trocar Scars
Comments Using serial gate-keeping to preserve the 5% overall type I error of 1-4 two-sided tests, 2-sided Wilcoxon Signed Rank tests were used. Computer graphics were used to display outcomes at Month 12, compare paired differences of outcomes between the 2 dosages and placebo, and show time trends in mean outcomes. Repeated measures regression models (GEE models in SAS/STAT PROC GENMOD) were used to examine longitudinal outcomes with terms for treatment and trocar location adjusted for key covariates.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.56
Comments For this early phase study, multiple comparisons adjustments were not used.
Method Wilcoxon (signed rank)
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection OSAS Results for Placebo Trocar Scars, OSAS Results for 3 mg AZX100 Trocar Scars
Comments Using serial gate-keeping to preserve the 5% overall type I error of 1-4 two-sided tests, 2-sided Wilcoxon Signed Rank tests were used. Computer graphics were used to display outcomes at Month 12, compare paired differences of outcomes between the 2 dosages and placebo, and show time trends in mean outcomes. Repeated measures regression models (GEE models in SAS/STAT PROC GENMOD) were used to examine longitudinal outcomes with terms for treatment and trocar location adjusted for key covariates.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.61
Comments For this early phase study, multiple comparisons adjustments were not used.
Method Wilcoxon (signed rank)
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection OSAS Results for Placebo Trocar Scars, OSAS Results for 10 mg AZX100 Trocar Scars
Comments Using serial gate-keeping to preserve the 5% overall type I error of 1-4 two-sided tests, 2-sided Wilcoxon Signed Rank tests were used. Computer graphics were used to display outcomes at Month 12, compare paired differences of outcomes between the 2 dosages and placebo, and show time trends in mean outcomes. Repeated measures regression models (GEE models in SAS/STAT PROC GENMOD) were used to examine longitudinal outcomes with terms for treatment and trocar location adjusted for key covariates.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.80
Comments For this early phase study, multiple comparisons adjustments were not used.
Method Wilcoxon (signed rank)
Comments [Not Specified]
2.Secondary Outcome
Title Between-group Mean Differences in Visual Analog Scale Scores Rated by Independent Blinded Raters Using 3D Photography
Hide Description Three trocar sites were randomized on each patient to receive AZX100 3 mg/cm or AZX100 10 mg/cm or saline placebo/cm at 9 days and 21 days after surgery. Twelve months after surgery, images of the trocar sites were longitudinally evaluated and rated using a standard 100 mm Visual Analog Scale (VAS) by two blinded independent dermatologists, with 0 being normal skin and 100 being the worst scar imaginable. Efficacy was based on the difference between VAS scores of placebo and 3 mg AZX100 and placebo and 10 mg AZX100 for each of the two raters separately. Data from both raters was not combined.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy analysis was based on patient data from the AZX100/Placebo cohort (i.e., not including patients receiving placebo-only). In the ITT sample for the VAS outcome, available sample sizes were 122 at Day 42 and 113 at Month 12 (including four subjects who withdrew from the study but were still followed for safety until Month 12).
Arm/Group Title Rater 1 VAS Scores for Placebo Trocar Scars Rater 1 VAS Scores for 3 mg AZX100 Trocar Scars Rater 1 VAS Scores for 10 mg AZX100 Trocar Scars Rater 2 VAS Scores for Placebo Trocar Scars Rater 2 VAS Scores for 3 mg AZX100 Trocar Scars Rater 2 VAS Scores for 10 mg AZX100 Trocar Scars
Hide Arm/Group Description:
This group included VAS scores at the 12 month time point for trocar scars that were randomized to receive saline placebo/cm at 9 days and 21 days following shoulder surgery.
This group included VAS scores at the 12 month time point for trocar scars that were randomized to receive AZX100 3 mg/cm at 9 days and 21 days following shoulder surgery.
This group included VAS scores at the 12 month time point for trocar scars that were randomized to receive AZX100 10 mg/cm at 9 days and 21 days following shoulder surgery.
This group included VAS scores at the 12 month time point for trocar scars that were randomized to receive saline placebo/cm at 9 days and 21 days following shoulder surgery.
This group included VAS scores at the 12 month time point for trocar scars that were randomized to receive AZX100 3 mg/cm at 9 days and 21 days following shoulder surgery.
This group included VAS scores at the 12 month time point for trocar scars that were randomized to receive AZX100 10 mg/cm at 9 days and 21 days following shoulder surgery.
Overall Number of Participants Analyzed 113 113 113 113 113 113
Mean (Standard Deviation)
Unit of Measure: Millimeters
10.96  (8.58) 11.78  (9.91) 11.86  (7.21) 17.23  (12.25) 17.49  (11.66) 18.49  (11.20)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rater 1 VAS Scores for Placebo Trocar Scars, Rater 1 VAS Scores for 3 mg AZX100 Trocar Scars
Comments Using a 100 mm VAS scale, each photograph was assessed by two raters, who, in an end-of-study session, were presented with photographs in their longitudinal sequence, but blinded as to dosage group. These data were used for an inter-rater concordance analysis and also to compare the placebo, 3 and 10 mg dosages.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.47
Comments For this early phase study, multiple comparisons adjustments were not used.
Method Wilcoxon (signed rank)
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Rater 1 VAS Scores for Placebo Trocar Scars, Rater 1 VAS Scores for 10 mg AZX100 Trocar Scars
Comments Using a 100 mm VAS scale, each photograph was assessed by two raters, who, in an end-of-study session, were presented with photographs in their longitudinal sequence, but blinded as to dosage group. These data were used for an inter-rater concordance analysis and also to compare the placebo, 3 and 10 mg dosages.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.080
Comments For this early phase study, multiple comparisons adjustments were not used.
Method Wilcoxon (signed rank)
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Rater 2 VAS Scores for Placebo Trocar Scars, Rater 2 VAS Scores for 3 mg AZX100 Trocar Scars
Comments Using a 100 mm VAS scale, each photograph was assessed by two raters, who, in an end-of-study session, were presented with photographs in their longitudinal sequence, but blinded as to dosage group. These data were used for an inter-rater concordance analysis and also to compare the placebo, 3 and 10 mg dosages.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.96
Comments For this early phase study, multiple comparisons adjustments were not used.
Method Wilcoxon (signed rank)
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Rater 2 VAS Scores for Placebo Trocar Scars, Rater 2 VAS Scores for 10 mg AZX100 Trocar Scars
Comments Using a 100 mm VAS scale, each photograph was assessed by two raters, who, in an end-of-study session, were presented with photographs in their longitudinal sequence, but blinded as to dosage group. These data were used for an inter-rater concordance analysis and also to compare the placebo, 3 and 10 mg dosages.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.22
Comments For this early phase study, multiple comparisons adjustments were not used.
Method Wilcoxon (signed rank)
Comments [Not Specified]
3.Secondary Outcome
Title Between-group Mean Differences in Objective Measures Via 3D Photography (Elevation, Length, Width)
Hide Description Three trocar sites designated as anterior, lateral and posterior were randomized on each patient to receive AZX100 3 mg/cm or AZX100 10 mg/cm or placebo/cm at 9 days and 21 days following shoulder surgery. 3D digital photography of each trocar scar was used to calculate scar length, width, minimum elevation, and maximum elevation in millimeters (mm) at 12 months. The minimum elevation value was calculated as the lowest point of the scar below the interpolated smooth skin surface. This was always a negative number. Negative values (closer to zero) were more desirable. The maximum elevation value was the highest point of the scar above the interpolated smooth skin surface. A smaller value was preferred.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy analysis was based on patient data from the AZX100/Placebo cohort (i.e., not including patients receiving placebo-only). In the ITT sample for the scar objective measures, available sample sizes were 122 at Day 42 and 113 at Month 12 (including four subjects who withdrew from the study but were still followed for safety until Month 12).
Arm/Group Title Scar Length for Placebo Trocar Scars Scar Length for 3 mg AZX100 Trocar Scars Scar Length for 10 mg AZX100 Trocar Scars Scar Width for Placebo Trocar Scars Scar Width for 3 mg AZX100 Trocar Scars Scar Width for 10 mg AZX100 Trocar Scars Scar Minimum Elevation for Placebo Trocar Scars Scar Minimum Elevation for 3 mg AZX100 Trocar Scars Scar Minimum Elevation for 10 mg AZX100 Trocar Scars Scar Maximum Elevation for Placebo Trocar Scars Scar Maximum Elevation for 3 mg AZX100 Trocar Scars Scar Maximum Elevation for 10 mg AZX100 Trocar Scars
Hide Arm/Group Description:
This group included scar length measurements at the 12 month time point for trocar scars that were randomized to receive saline placebo/cm at 9 days and 21 days following shoulder surgery.
This group included scar length measurements at the 12 month time point for trocar scars that were randomized to receive AZX100 3 mg/cm at 9 days and 21 days following shoulder surgery.
This group included scar length measurements at the 12 month time point for trocar scars that were randomized to receive AZX100 10 mg/cm at 9 days and 21 days following shoulder surgery.
This group included scar width measurements at the 12 month time point for trocar scars that were randomized to receive saline placebo/cm at 9 days and 21 days following shoulder surgery.
This group included scar width measurements at the 12 month time point for trocar scars that were randomized to receive AZX100 3 mg/cm at 9 days and 21 days following shoulder surgery.
This group included scar width measurements at the 12 month time point for trocar scars that were randomized to receive AZX100 10 mg/cm at 9 days and 21 days following shoulder surgery.
This group included scar minimum elevation measurements at the 12 month time point for trocar scars that were randomized to receive AZX100 saline placebo/cm at 9 days and 21 days following shoulder surgery.
This group included scar minimum elevation measurements at the 12 month time point for trocar scars that were randomized to receive AZX100 3 mg/cm at 9 days and 21 days following shoulder surgery.
This group included scar minimum elevation measurements at the 12 month time point for trocar scars that were randomized to receive AZX100 10 mg/cm at 9 days and 21 days following shoulder surgery.
This group included scar maximum elevation measurements at the 12 month time point for trocar scars that were randomized to receive saline placebo/cm at 9 days and 21 days following shoulder surgery.
This group included scar maximum elevation measurements at the 12 month time point for trocar scars that were randomized to receive AZX100 3 mg/cm at 9 days and 21 days following shoulder surgery.
This group included scar maximum elevation measurements at the 12 month time point for trocar scars that were randomized to receive AZX100 10 mg/cm at 9 days and 21 days following shoulder surgery.
Overall Number of Participants Analyzed 113 113 113 113 113 113 113 113 113 113 113 113
Mean (Standard Deviation)
Unit of Measure: Millimeters
8.75  (4.12) 8.74  (3.70) 9.59  (3.84) 2.62  (1.50) 2.59  (1.31) 2.71  (1.35) -0.26  (0.19) -0.29  (0.21) -0.27  (0.20) 0.19  (0.17) 0.18  (0.13) 0.19  (0.13)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Scar Length for Placebo Trocar Scars, Scar Length for 3 mg AZX100 Trocar Scars
Comments Statistical analysis included line plots of paired differences vs. time, univariate p-values from Wilcoxon signed rank tests, and repeated measures regression models in SAS/STAT PROC GENMOD.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.87
Comments For this early phase study, multiple comparisons adjustments were not used.
Method Wilcoxon (signed rank)
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Scar Length for Placebo Trocar Scars, Scar Length for 10 mg AZX100 Trocar Scars
Comments Statistical analysis included line plots of paired differences vs. time, univariate p-values from Wilcoxon signed rank tests, and repeated measures regression models in SAS/STAT PROC GENMOD.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.15
Comments For this early phase study, multiple comparisons adjustments were not used.
Method Wilcoxon (signed rank)
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Scar Width for Placebo Trocar Scars, Scar Width for 3 mg AZX100 Trocar Scars
Comments Statistical analysis included line plots of paired differences vs. time, univariate p-values from Wilcoxon signed rank tests, and repeated measures regression models in SAS/STAT PROC GENMOD.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.77
Comments For this early phase study, multiple comparisons adjustments were not used.
Method Wilcoxon (signed rank)
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Scar Width for Placebo Trocar Scars, Scar Width for 10 mg AZX100 Trocar Scars
Comments Statistical analysis included line plots of paired differences vs. time, univariate p-values from Wilcoxon signed rank tests, and repeated measures regression models in SAS/STAT PROC GENMOD.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.75
Comments For this early phase study, multiple comparisons adjustments were not used.
Method Wilcoxon (signed rank)
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Scar Minimum Elevation for Placebo Trocar Scars, Scar Minimum Elevation for 3 mg AZX100 Trocar Scars
Comments Statistical analysis included line plots of paired differences vs. time, univariate p-values from Wilcoxon signed rank tests, and repeated measures regression models in SAS/STAT PROC GENMOD.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.050
Comments For this early phase study, multiple comparisons adjustments were not used.
Method Wilcoxon (signed rank)
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Scar Minimum Elevation for Placebo Trocar Scars, Scar Minimum Elevation for 10 mg AZX100 Trocar Scars
Comments Statistical analysis included line plots of paired differences vs. time, univariate p-values from Wilcoxon signed rank tests, and repeated measures regression models in SAS/STAT PROC GENMOD.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.83
Comments For this early phase study, multiple comparisons adjustments were not used.
Method Wilcoxon (signed rank)
Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Scar Maximum Elevation for Placebo Trocar Scars, Scar Maximum Elevation for 3 mg AZX100 Trocar Scars
Comments Statistical analysis included line plots of paired differences vs. time, univariate p-values from Wilcoxon signed rank tests, and repeated measures regression models in SAS/STAT PROC GENMOD.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.37
Comments For this early phase study, multiple comparisons adjustments were not used.
Method Wilcoxon (signed rank)
Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Scar Maximum Elevation for Placebo Trocar Scars, Scar Maximum Elevation for 10 mg AZX100 Trocar Scars
Comments Statistical analysis included line plots of paired differences vs. time, univariate p-values from Wilcoxon signed rank tests, and repeated measures regression models in SAS/STAT PROC GENMOD.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.43
Comments For this early phase study, multiple comparisons adjustments were not used.
Method Wilcoxon (signed rank)
Comments [Not Specified]
4.Secondary Outcome
Title Between-group Mean Differences in Objective Measures Via 3D Photography (Volume)
Hide Description Three trocar sites designated as anterior, lateral and posterior were randomized on each patient to receive AZX100 3 mg/cm, or AZX100 10 mg/cm, or placebo/cm at 9 days and 21 days following shoulder surgery. 3D digital photography of each trocar scar was used to calculate positive volume, negative volume, and total volume in millimeters cubed (mm^3) at 12 months. Positive volume included the scar volume that was calculated to be above the interpolated smooth skin surface. A smaller value was preferred. Negative volume included the volume of the scar calculated to be below the interpolated smooth skin surface. It was always a negative number; negative values (closer to zero) were more desirable. Total volume was calculated as the sum of positive volume and the absolute value of negative volume. Smaller values were more desirable.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy analysis was based on patient data from the AZX100/Placebo cohort (i.e., not including patients receiving placebo-only). In the ITT sample for the scar objective measures, available sample sizes were 122 at Day 42 and 113 at Month 12 (including four subjects who withdrew from the study but were still followed for safety until Month 12).
Arm/Group Title Scar Positive Volume for Placebo Trocar Scars Scar Positive Volume for 3 mg AZX100 Trocar Scars Scar Positive Volume for 10 mg AZX100 Trocar Scars Scar Negative Volume for Placebo Trocar Scars Scar Negative Volume for 3 mg AZX100 Trocar Scars Scar Negative Volume for 10 mg AZX100 Trocar Scars Scar Total Volume for Placebo Trocar Scars Scar Total Volume for 3 mg AZX100 Trocar Scars Scar Total Volume for 10 mg AZX100 Trocar Scars
Hide Arm/Group Description:
This group included scar positive volume measurements at the 12 month time point for trocar scars that were randomized to receive saline placebo/cm at 9 days and 21 days following shoulder surgery.
This group included scar positive volume measurements at the 12 month time point for trocar scars that were randomized to receive AZX100 3 mg/cm at 9 days and 21 days following shoulder surgery.
This group included scar positive volume measurements at the 12 month time point for trocar scars that were randomized to receive AZX100 10 mg/cm at 9 days and 21 days following shoulder surgery.
This group included scar negative volume measurements at the 12 month time point for trocar scars that were randomized to receive saline placebo/cm at 9 days and 21 days following shoulder surgery.
This group included scar negative volume measurements at the 12 month time point for trocar scars that were randomized to receive AZX100 3 mg/cm at 9 days and 21 days following shoulder surgery.
This group included scar negative volume measurements at the 12 month time point for trocar scars that were randomized to receive AZX100 10 mg/cm at 9 days and 21 days following shoulder surgery.
This group included scar total volume measurements at the 12 month time point for trocar scars that were randomized to receive saline placebo/cm at 9 days and 21 days following shoulder surgery.
This group included scar total volume measurements at the 12 month time point for trocar scars that were randomized to receive AZX100 3 mg/cm at 9 days and 21 days following shoulder surgery.
This group included scar total volume measurements at the 12 month time point for trocar scars that were randomized to receive AZX100 10 mg/cm at 9 days and 21 days following shoulder surgery.
Overall Number of Participants Analyzed 113 113 113 113 113 113 113 113 113
Mean (Standard Deviation)
Unit of Measure: Millimeters cubed
4.74  (8.95) 4.05  (4.25) 4.44  (4.46) -8.42  (8.66) -9.44  (12.77) -9.59  (13.01) 13.16  (11.53) 13.49  (13.36) 14.03  (13.68)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Scar Positive Volume for Placebo Trocar Scars, Scar Positive Volume for 3 mg AZX100 Trocar Scars
Comments Statistical analysis included line plots of paired differences vs. time, univariate p-values from Wilcoxon signed rank tests, and repeated measures regression models in SAS/STAT PROC GENMOD.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.16
Comments For this early phase study, multiple comparisons adjustments were not used.
Method Wilcoxon (signed rank)
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Scar Positive Volume for Placebo Trocar Scars, Scar Positive Volume for 10 mg AZX100 Trocar Scars
Comments Statistical analysis included line plots of paired differences vs. time, univariate p-values from Wilcoxon signed rank tests, and repeated measures regression models in SAS/STAT PROC GENMOD.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.14
Comments For this early phase study, multiple comparisons adjustments were not used.
Method Wilcoxon (signed rank)
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Scar Negative Volume for Placebo Trocar Scars, Scar Negative Volume for 3 mg AZX100 Trocar Scars
Comments Statistical analysis included line plots of paired differences vs. time, univariate p-values from Wilcoxon signed rank tests, and repeated measures regression models in SAS/STAT PROC GENMOD.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.69
Comments For this early phase study, multiple comparisons adjustments were not used.
Method Wilcoxon (signed rank)
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Scar Negative Volume for Placebo Trocar Scars, Scar Negative Volume for 10 mg AZX100 Trocar Scars
Comments Statistical analysis included line plots of paired differences vs. time, univariate p-values from Wilcoxon signed rank tests, and repeated measures regression models in SAS/STAT PROC GENMOD.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.89
Comments For this early phase study, multiple comparisons adjustments were not used.
Method Wilcoxon (signed rank)
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Scar Total Volume for Placebo Trocar Scars, Scar Total Volume for 3 mg AZX100 Trocar Scars
Comments Statistical analysis included line plots of paired differences vs. time, univariate p-values from Wilcoxon signed rank tests, and repeated measures regression models in SAS/STAT PROC GENMOD.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.30
Comments For this early phase study, multiple comparisons adjustments were not used.
Method Wilcoxon (signed rank)
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Scar Total Volume for Placebo Trocar Scars, Scar Total Volume for 10 mg AZX100 Trocar Scars
Comments Statistical analysis included line plots of paired differences vs. time, univariate p-values from Wilcoxon signed rank tests, and repeated measures regression models in SAS/STAT PROC GENMOD.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.46
Comments For this early phase study, multiple comparisons adjustments were not used.
Method Wilcoxon (signed rank)
Comments [Not Specified]
5.Secondary Outcome
Title Histological Evaluation of Collagen
Hide Description Three trocar sites designated as anterior, lateral and posterior were randomized on each patient to receive AZX100 3 mg/cm or AZX100 10 mg/cm or placebo/cm at 9 days and 21 days following shoulder surgery. A skin punch biopsy was taken of each trocar site at 12 months. The specimens were blindly scored in duplicate by a dermal pathologist for dermal collagen fiber density, maturity and orientation, where 0% was completely normal and 100% was completely abnormal.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis was based on patient data from the AZX100/Placebo cohort (i.e., not including patients receiving placebo-only). In the ITT sample for the histology analyses, available sample sizes were 122 at Day 42 and 113 at Month 12 (including four subjects who withdrew from the study but were still followed for safety until Month 12).
Arm/Group Title Collagen Fiber Density Results for Placebo Scars Collagen Fiber Density Results for 3 mg AZX100 Scars Collagen Fiber Density Results for 10 mg AZX100 Scars Collagen Fiber Maturity Results for Placebo Scars Collagen Fiber Maturity Results for 3 mg AZX100 Scars Collagen Fiber Maturity Results for 10 mg AZX100 Scars Collagen Fiber Orientation Results for Placebo Scars Collagen Fiber Orientation Results for 3 mg AZX100 Scars Collagen Fiber Orientation Results for 10 mg AZX100 Scars
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This group included results for collagen fiber density at the 12 month time point for trocar scars that were randomized to receive saline placebo/cm at 9 days and 21 days following shoulder surgery.
This group included results for collagen fiber density at the 12 month time point for trocar scars that were randomized to receive AZX100 3 mg/cm at 9 days and 21 days following shoulder surgery.
This group included results for collagen fiber density at the 12 month time point for trocar scars that were randomized to receive AZX100 10 mg/cm at 9 days and 21 days following shoulder surgery.
This group included results for collagen fiber maturity at the 12 month time point for trocar scars that were randomized to receive saline placebo/cm at 9 days and 21 days following shoulder surgery.
This group included results for collagen fiber maturity at the 12 month time point for trocar scars that were randomized to receive AZX100 3 mg/cm at 9 days and 21 days following shoulder surgery.
This group included results for collagen fiber maturity at the 12 month time point for trocar scars that were randomized to receive AZX100 10 mg/cm at 9 days and 21 days following shoulder surgery.
This group included results for collagen fiber orientation at the 12 month time point for trocar scars that were randomized to receive saline placebo/cm at 9 days and 21 days following shoulder surgery.
This group included results for collagen fiber orientation at the 12 month time point for trocar scars that were randomized to receive AZX100 3 mg/cm at 9 days and 21 days following shoulder surgery.
This group included results for collagen fiber orientation at the 12 month time point for trocar scars that were randomized to receive AZX100 10 mg/cm at 9 days and 21 days following shoulder surgery.
Overall Number of Participants Analyzed 113 113 113 113 113 113 113 113 113
Mean (Standard Deviation)
Unit of Measure: Percent
24.20  (24.08) 19.43  (21.79) 25.34  (23.18) 22.72  (23.59) 17.95  (21.52) 23.64  (22.68) 23.41  (24.54) 18.52  (21.73) 24.77  (24.00)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Collagen Fiber Density Results for Placebo Scars, Collagen Fiber Density Results for 3 mg AZX100 Scars
Comments Agreement between the two rater evaluations was assessed by tabulating the difference of the two ratings. Statistical methods for paired data were used to compare the two dosages of AZX100 to placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.086
Comments For this early phase study, multiple comparisons adjustments were not used.
Method Wilcoxon (signed rank)
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Collagen Fiber Density Results for Placebo Scars, Collagen Fiber Density Results for 10 mg AZX100 Scars
Comments Agreement between the two rater evaluations was assessed by tabulating the difference of the two ratings. Statistical methods for paired data were used to compare the two dosages of AZX100 to placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.66
Comments For this early phase study, multiple comparisons adjustments were not used.
Method Wilcoxon (signed rank)
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Collagen Fiber Maturity Results for Placebo Scars, Collagen Fiber Maturity Results for 3 mg AZX100 Scars
Comments Agreement between the two rater evaluations was assessed by tabulating the difference of the two ratings. Statistical methods for paired data were used to compare the two dosages of AZX100 to placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.069
Comments For this early phase study, multiple comparisons adjustments were not used.
Method Wilcoxon (signed rank)
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Collagen Fiber Maturity Results for Placebo Scars, Collagen Fiber Maturity Results for 10 mg AZX100 Scars
Comments Agreement between the two rater evaluations was assessed by tabulating the difference of the two ratings. Statistical methods for paired data were used to compare the two dosages of AZX100 to placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.68
Comments For this early phase study, multiple comparisons adjustments were not used.
Method Wilcoxon (signed rank)
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Collagen Fiber Orientation Results for Placebo Scars, Collagen Fiber Orientation Results for 3 mg AZX100 Scars
Comments Agreement between the two rater evaluations was assessed by tabulating the difference of the two ratings. Statistical methods for paired data were used to compare the two dosages of AZX100 to placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.095
Comments For this early phase study, multiple comparisons adjustments were not used.
Method Wilcoxon (signed rank)
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Collagen Fiber Orientation Results for Placebo Scars, Collagen Fiber Orientation Results for 10 mg AZX100 Scars
Comments Agreement between the two rater evaluations was assessed by tabulating the difference of the two ratings. Statistical methods for paired data were used to compare the two dosages of AZX100 to placebo.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.62
Comments For this early phase study, multiple comparisons adjustments were not used.
Method Wilcoxon (signed rank)
Comments [Not Specified]
6.Secondary Outcome
Title Histological Evaluation of Number of Alpha Smooth Muscle Actin Cells
Hide Description Three trocar sites designated as anterior, lateral and posterior were randomized on each patient to receive AZX100 3 mg/cm or AZX100 10 mg/cm or placebo/cm at 9 days and 21 days following shoulder surgery. A skin punch biopsy was taken of each trocar site at 12 months. For exploratory purposes, the specimens were blindly scored in duplicate by a dermal pathologist for the estimated number of alpha-smooth muscle actin (α-SMA) positive cells per high powered field. Values ranged from 0 to several hundred. The number of α-SMA cells was assessed for exploratory purposes; therefore, at the time of this report, it was not known whether it was better to have a low or high α-SMA score.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis was based on patient data from the AZX100/Placebo cohort (i.e., not including patients receiving placebo-only). In the ITT sample for the histology analyses, available sample sizes were 122 at Day 42 and 113 at Month 12 (including four subjects who withdrew from the study but were still followed for safety until Month 12).
Arm/Group Title Alpha SMA Results for Placebo Trocar Scars Alpha SMA Results for 3 mg AZX100 Trocar Scars Alpha SMA Results for 10 mg AZX100 Trocar Scars
Hide Arm/Group Description:
This group included assessment for α-SMA at the 12 month time point for trocar scars that were randomized to receive saline placebo/cm at 9 days and 21 days following shoulder surgery.
This group included assessment for α-SMA at the 12 month time point for trocar scars that were randomized to receive AZX100 3 mg/cm at 9 days and 21 days following shoulder surgery.
This group included assessment for α-SMA at the 12 month time point for trocar scars that were randomized to receive AZX100 10 mg/cm at 9 days and 21 days following shoulder surgery.
Overall Number of Participants Analyzed 113 113 113
Mean (Standard Deviation)
Unit of Measure: Cells per high-powered field
22.07  (47.02) 24.78  (58.25) 32.80  (64.56)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alpha SMA Results for Placebo Trocar Scars, Alpha SMA Results for 3 mg AZX100 Trocar Scars
Comments A regression analysis was run to compare alpha-SMA between 3 mg and 10 mg AZX100 and placebo, adjusted for the subject’s gender and age. GEE regression in SAS/STAT PROC GENMOD was used because it properly handled the correlations among the three observations for each subject.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.44
Comments [Not Specified]
Method Wilcoxon (signed rank)
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Alpha SMA Results for Placebo Trocar Scars, Alpha SMA Results for 10 mg AZX100 Trocar Scars
Comments A regression analysis was run to compare alpha-SMA between 3 mg and 10 mg AZX100 and placebo, adjusted for the subject’s gender and age. GEE regression in SAS/STAT PROC GENMOD was used because it properly handled the correlations among the three observations for each subject.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.41
Comments [Not Specified]
Method Wilcoxon (signed rank)
Comments [Not Specified]
Time Frame Adverse events began to be collected for each patient after dosing with study agent, and were collected for the duration of the study (12 months). The adverse event collection period for the entire study lasted for a period of 24 months.
Adverse Event Reporting Description All 150 treated subjects were included in the adverse event analyses. Two groups were compared: 126 subjects who received placebo, 3 mg/cm, and 10 mg/cm of AZX100 at three shoulder trocar sites; and 24 subjects who received only placebo at three shoulder trocar sites.
 
Arm/Group Title AZX100-Placebo Arm Placebo-only Arm
Hide Arm/Group Description Three trocar sites designated as anterior, lateral and posterior will be randomized on each patient to receive one low dose of AZX100, one high dose of AZX100, or placebo. Three trocar sites on each patient will receive one dose of placebo.
All-Cause Mortality
AZX100-Placebo Arm Placebo-only Arm
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
AZX100-Placebo Arm Placebo-only Arm
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   8/126 (6.35%)      2/24 (8.33%)    
Cardiac disorders     
Coronary Artery Occlusion  1/126 (0.79%)  1 0/24 (0.00%)  0
Myocardial Infarction  1/126 (0.79%)  1 0/24 (0.00%)  0
General disorders     
Chest Pain  1/126 (0.79%)  1 1/24 (4.17%)  1
Hepatobiliary disorders     
Cholecystitis, Acute  1/126 (0.79%)  1 0/24 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Kyphosis  1/126 (0.79%)  1 0/24 (0.00%)  0
Musculoskeletal Pain  1/126 (0.79%)  1 1/24 (4.17%)  1
Osteoarthritis  1/126 (0.79%)  1 0/24 (0.00%)  0
Pseudarthrosis  1/126 (0.79%)  1 0/24 (0.00%)  0
Nervous system disorders     
Transient Ischemic Attack  1/126 (0.79%)  1 0/24 (0.00%)  0
Psychiatric disorders     
Anxiety  1/126 (0.79%)  1 0/24 (0.00%)  0
Renal and urinary disorders     
Nephrolithiasis  1/126 (0.79%)  1 0/24 (0.00%)  0
Vascular disorders     
Hypertension  1/126 (0.79%)  1 0/24 (0.00%)  0
1
Term from vocabulary, MedDRA (12.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
AZX100-Placebo Arm Placebo-only Arm
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   125/126 (99.21%)      21/24 (87.50%)    
Gastrointestinal disorders     
Nausea  8/126 (6.35%)  8 1/24 (4.17%)  1
Vomiting  3/126 (2.38%)  3 2/24 (8.33%)  2
General disorders     
Fatigue  0/126 (0.00%)  0 2/24 (8.33%)  4
Injection Site Erythema 1 [1]  46/126 (36.51%)  106 3/24 (12.50%)  5
Injection Site Irritation 1 [1]  63/126 (50.00%)  163 6/24 (25.00%)  15
Injection Site Pain 1 [1]  80/126 (63.49%)  246 7/24 (29.17%)  23
Injection Site Pruritus 1 [1]  14/126 (11.11%)  21 2/24 (8.33%)  5
Injection Site Urticaria 1 [1]  24/126 (19.05%)  61 1/24 (4.17%)  3
Oedema Peripheral  2/126 (1.59%)  2 2/24 (8.33%)  2
Infections and infestations     
Influenza  2/126 (1.59%)  2 3/24 (12.50%)  3
Nasopharyngitis  8/126 (6.35%)  8 1/24 (4.17%)  1
Sinusitis  10/126 (7.94%)  12 0/24 (0.00%)  0
Upper Respiratory Tract Infection  19/126 (15.08%)  26 6/24 (25.00%)  6
Injury, poisoning and procedural complications     
Arthropod Bite  0/126 (0.00%)  0 2/24 (8.33%)  3
Musculoskeletal and connective tissue disorders     
Arthralgia  9/126 (7.14%)  11 1/24 (4.17%)  1
Back Pain  5/126 (3.97%)  7 4/24 (16.67%)  4
Musculoskeletal Pain  12/126 (9.52%)  17 2/24 (8.33%)  4
Nervous system disorders     
Dizziness  7/126 (5.56%)  7 2/24 (8.33%)  3
Headache  7/126 (5.56%)  7 3/24 (12.50%)  6
1
Term from vocabulary, MedDRA (12.0)
[1]
Special note for injection site adverse events: There were three trocar treatment areas on the shoulder; therefore, a participant could have the same and/or different injection site events at all three trocar treatment sites simultaneously.
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: Denise Lamon
Organization: Capstone Therapeutics Corp.
Phone: 602-286-5206
EMail: dlamon@capstonethx.com
Layout table for additonal information
Responsible Party: Capstone Therapeutics
ClinicalTrials.gov Identifier: NCT00811577     History of Changes
Other Study ID Numbers: OL-ASCAR-03
First Submitted: December 18, 2008
First Posted: December 19, 2008
Results First Submitted: May 16, 2012
Results First Posted: October 11, 2012
Last Update Posted: October 11, 2012