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Study to Evaluate the Safety and Efficacy of Aceneuramic Acid Extended-Release (Ace-ER) Tablets in Patients With Glucosamine (UDP-N-acetyl)-2-epimerase Myopathy (GNEM) or Hereditary Inclusion Body Myopathy (HIBM)

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: NCT02736188
Recruitment Status : Terminated
First Posted : April 13, 2016
Results First Posted : February 19, 2019
Last Update Posted : February 19, 2019
Sponsor:
Information provided by (Responsible Party):
Ultragenyx Pharmaceutical Inc

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Hereditary Inclusion Body Myopathy
Distal Myopathy With Rimmed Vacuoles
Distal Myopathy, Nonaka Type
GNE Myopathy
Quadriceps Sparing Myopathy
Intervention Drug: Aceneuramic Acid Extended-Release Tablets
Enrollment 143
Recruitment Details 143 participants were screened and enrolled across 14 total sites in the United States, Israel, United Kingdom, Italy, France, Canada, and Bulgaria. 87 participants rolled over from study UX001-CL301 (NCT02377921), 49 participants rolled over from study UX001-CL202 (NCT01830972), and 7 participants rolled over from UX001-CL203 (NCT02731690).
Pre-assignment Details Of the143 participants who enrolled, 1 participant withdrew consent prior to receiving the first dose and is not included in the Safety Analysis Population presented below.
Arm/Group Title Ace-ER 6 g/Day
Hide Arm/Group Description 4 tablets (500 mg Ace-ER each for 2 g per dose) orally 3 times per day
Period Title: Overall Study
Started 142
Completed 0
Not Completed 142
Reason Not Completed
Discontinuation of Study by Sponsor             134
Adverse Event             1
Withdrawal by Subject             1
Other             6
Arm/Group Title Ace-ER 6 g/Day
Hide Arm/Group Description 4 tablets (500 mg Ace-ER each for 2 g per dose) orally 3 times per day
Overall Number of Baseline Participants 142
Hide Baseline Analysis Population Description
Safety Analysis Set: all participants who received at least one dose of study drug in UX001-CL302.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 142 participants
74  (68)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 142 participants
Female
74
  52.1%
Male
68
  47.9%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 142 participants
Hispanic or Latino
14
   9.9%
Not Hispanic or Latino
125
  88.0%
Unknown or Not Reported
3
   2.1%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
White Number Analyzed 142 participants
111
  78.2%
Asian Number Analyzed 142 participants
19
  13.4%
Other, Not Specified Number Analyzed 142 participants
12
   8.5%
Hand Held Dynamometry (HHD) Upper Extremity Composite Score (UEC)   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Kgf
Number Analyzed 87 participants
52.98  (28.814)
[1]
Measure Description: Hand held dynamometry testing was used to measure strength. The maximum voluntary isometric contraction against a dynamometer was used to measure bilateral strength in the following muscle groups: shoulder abductors, wrist extensors and knee extensors. Specialized dynamometers for the measurement of grip and key pinch strength were also used. The total force (in kilogram-force [kgf]) for each was recorded.
[2]
Measure Analysis Population Description: Full Analysis Set: all participants in parent study UX001-CL301 (NCT02377921) with a UX001-CL302 baseline measurement and at least one post-baseline measurement in UX001-CL302.
Glucosamine (UDP-N-acetyl)-2-epimerase Myopathy Functional Activities Scale(GNEM-FAS) Mobility Score   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Score on a scale
Number Analyzed 87 participants
24.17  (7.772)
[1]
Measure Description: GNEM-FAS Expanded Version Mobility subscale score has 13 items and ranges from 0 to 52 with higher scores representing greater mobility.
[2]
Measure Analysis Population Description: Full Analysis Set: all participants in parent study UX001-CL301 (NCT02377921) with a UX001-CL302 baseline measurement and at least one post-baseline measurement in UX001-CL302.
GNEM-FAS Expanded Version Upper Extremity Score   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Score on a scale
Number Analyzed 87 participants
27.53  (4.938)
[1]
Measure Description: GNEM-FAS Expanded Version Upper Extremity subscale score has 9 items and ranges from 0 to 36 with higher scores representing more skilled, independent use of the arms during functional activity performance.
[2]
Measure Analysis Population Description: Full Analysis Set: all participants in parent study UX001-CL301 (NCT02377921) with a UX001-CL302 baseline measurement and at least one post-baseline measurement in UX001-CL302.
HHD Lower Extremity Composite (LEC) Score   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Kgf
Number Analyzed 86 participants
51.91  (37.474)
[1]
Measure Description: Hand held dynamometry testing was used to measure strength. The maximum voluntary isometric contraction against a dynamometer was used to measure bilateral strength in the following muscle groups: shoulder abductors, wrist extensors and knee extensors. Specialized dynamometers for the measurement of grip and key pinch strength were also used. The total force (in kgf) for each was recorded.
[2]
Measure Analysis Population Description: Full Analysis Set: all participants in parent study UX001-CL301 (NCT02377921) with a UX001-CL302 baseline measurement and at least one post-baseline measurement in UX001-CL302.
Sit-to-Stand Test   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Stands
Number Analyzed 87 participants
12.75  (4.977)
[1]
Measure Description: Lower extremity function was assessed using a sit-to-stand test. The number of times the participant can rise from a seated to a standing position in a 30-second period was recorded.
[2]
Measure Analysis Population Description: Full Analysis Set: all participants in parent study UX001-CL301 (NCT02377921) with a UX001-CL302 baseline measurement and at least one post-baseline measurement in UX001-CL302.
30-second Weighted Arm Lift Test   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Lifts
Number Analyzed 72 participants
30.93  (13.171)
[1]
Measure Description: Upper extremity function was assessed using a weighted arm lift test performed bilaterally. The number of times the participant can raise a 1 kg weight above the head in a 30-second period was recorded.
[2]
Measure Analysis Population Description: Full Analysis Set: all participants in parent study UX001-CL301 (NCT02377921) with a UX001-CL302 baseline measurement and at least one post-baseline measurement in UX001-CL302.
Six-Minute Walk Test (6MWT)   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Meters
Number Analyzed 83 participants
359.4  (123.94)
[1]
Measure Description: The total distance walked (meters) in a 6-minute period was measured.
[2]
Measure Analysis Population Description: Full Analysis Set: all participants in parent study UX001-CL301 (NCT02377921) with a UX001-CL302 baseline measurement and at least one post-baseline measurement in UX001-CL302.
Percent Predicted Meters Walked in 6MWT   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Percentage of predicted meters
Number Analyzed 83 participants
49.52  (16.962)
[1]
Measure Description: The total distance walked (meters) in a 6-minute period was measured, and the percent predicted distance based on normative data for age and gender was estimated. Predicted 6MWT distance (meters) = 868.8 - (2.99 x Age) - (74.7 x Sex), where age is baseline age in years, and sex = 0 for males, and 1 for females.
[2]
Measure Analysis Population Description: Full Analysis Set: all participants in parent study UX001-CL301 (NCT02377921) with a UX001-CL302 baseline measurement and at least one post-baseline measurement in UX001-CL302.
Total Force in Knee Extensors   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Kgf
Number Analyzed 84 participants
26.60  (9.746)
[1]
Measure Description: Hand held dynamometry testing was used to measure strength. The maximum voluntary isometric contraction against a dynamometer was used to measure bilateral strength in the following muscle groups: shoulder abductors, wrist extensors and knee extensors. Specialized dynamometers for the measurement of grip and key pinch strength were also used. The total force (in kgf) for each was recorded.
[2]
Measure Analysis Population Description: Full Analysis Set: all participants in parent study UX001-CL301 (NCT02377921) with a UX001-CL302 baseline measurement and at least one post-baseline measurement in UX001-CL302.
Percent of Predicted Total Force in Knee Extensors   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Percent of predicted total force
Number Analyzed 81 participants
13.69  (15.323)
[1]
Measure Description: The percent predicted total force value of lower extremity muscle strength in the knee extensors was determined based on reference equations adjusting for age, gender, height, and weight.
[2]
Measure Analysis Population Description: Full Analysis Set: all participants in parent study UX001-CL301 (NCT02377921) with a UX001-CL302 baseline measurement and at least one post-baseline measurement in UX001-CL302.
1.Primary Outcome
Title Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious AEs (SAEs), and Discontinuations Due to AEs
Hide Description An AE was defined as any untoward medical occurrence associated with the use of a drug, whether or not considered drug related. An SAE or serious suspected adverse reaction is an AE or suspected adverse reaction that at any dose, in the view of either the Investigator or Ultragenyx, results in any of the following outcomes: death; a life-threatening AE; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant incapacity or disability (substantial disruption of the ability to conduct normal life functions); congenital anomaly/birth defect. TEAEs were defined as any AE that occurred after the first dose of study drug. The severity of all AEs were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03: grade1=mild, grade 2=moderate, grade 3=severe, grade 4=life-threatening, grade 5=death.
Time Frame From first dose of study drug through the end of treatment plus 30 days (+5 days). Mean (SD) duration of treatment was 256.3 (101.54) days.
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set: all participants who received at least one dose of study drug in UX001-CL302.
Arm/Group Title Ace-ER 6 g/Day
Hide Arm/Group Description:
4 tablets (500 mg Ace-ER each for 2 g per dose) orally 3 times per day
Overall Number of Participants Analyzed 142
Measure Type: Count of Participants
Unit of Measure: Participants
TEAEs
104
  73.2%
Serious TEAEs (SAEs)
7
   4.9%
Deaths
0
   0.0%
Grade 3 or 4 TEAEs
11
   7.7%
TEAEs Leading to Study Drug Discontinuation
2
   1.4%
TEAEs Leading to Study Discontinuation
1
   0.7%
2.Primary Outcome
Title Change From Baseline in HHD UEC Score Over Time
Hide Description Hand held dynamometry testing was used to measure strength. The maximum voluntary isometric contraction against a dynamometer was used to measure bilateral strength in the following muscle groups: shoulder abductors, wrist extensors and knee extensors. Specialized dynamometers for the measurement of grip and key pinch strength were also used. The total force (in kgf) for each was recorded. The UEC is derived from the sum of the average of the right and left total force (measured in kgf). Analyzed using a repeated measure generalized estimation equation (GEE) model, which includes the baseline value as a covariate.
Time Frame Baseline, Weeks 8, 16, 24, 48
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all participants in parent study UX001-CL301 (NCT02377921) with a UX001-CL302 baseline measurement and at least one post-baseline measurement in UX001-CL302.
Arm/Group Title Ace-ER 6 g/Day (Parent Study Treatment: Ace-ER 6 g/Day) Ace-ER 6 g/Day (Parent Study Treatment: Placebo)
Hide Arm/Group Description:
4 tablets (500 mg Ace-ER each for 2 g per dose) orally 3 times per day in participants who took Ace-ER in study UX001-CL301 (NCT02377921)
4 tablets (500 mg Ace-ER each for 2 g per dose) orally 3 times per day in participants who took placebo in study UX001-CL301 (NCT02377921)
Overall Number of Participants Analyzed 44 43
Least Squares Mean (95% Confidence Interval)
Unit of Measure: kgf
Week 8
0.88
(-0.75 to 2.51)
0.09
(-1.05 to 1.23)
Week 16
0.10
(-1.47 to 1.67)
-0.26
(-1.26 to 0.74)
Week 24
-1.40
(-2.92 to 0.12)
-0.49
(-2.13 to 1.15)
Week 48
-2.24
(-4.95 to 0.47)
-2.18
(-4.30 to -0.07)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ace-ER 6 g/Day (Parent Study Treatment: Ace-ER 6 g/Day), Ace-ER 6 g/Day (Parent Study Treatment: Placebo)
Comments Week 8
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4287
Comments Baseline is fit into the model as a covariate.
Method generalized estimating equation (GEE)
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.80
Confidence Interval (2-Sided) 95%
-1.17 to 2.77
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ace-ER 6 g/Day (Parent Study Treatment: Ace-ER 6 g/Day), Ace-ER 6 g/Day (Parent Study Treatment: Placebo)
Comments Week 16
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7031
Comments Baseline is fit into the model as a covariate.
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.36
Confidence Interval (2-Sided) 95%
-1.49 to 2.21
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ace-ER 6 g/Day (Parent Study Treatment: Ace-ER 6 g/Day), Ace-ER 6 g/Day (Parent Study Treatment: Placebo)
Comments Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4253
Comments Baseline is fit into the model as a covariate.
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.91
Confidence Interval (2-Sided) 95%
-3.14 to 1.32
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Ace-ER 6 g/Day (Parent Study Treatment: Ace-ER 6 g/Day), Ace-ER 6 g/Day (Parent Study Treatment: Placebo)
Comments Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9747
Comments Baseline is fit into the model as a covariate.
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.06
Confidence Interval (2-Sided) 95%
-3.49 to 3.38
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline in the GNEM-FAS Expanded Version Mobility Domain Score Over Time
Hide Description GNEM-FAS Expanded Version Mobility subscale score has 13 items and ranges from 0 to 52 with higher scores representing greater mobility. Analyzed using a repeated measure GEE model, which includes the baseline value as a covariate.
Time Frame Baseline, Weeks 8, 16, 24, 48
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all participants in parent study UX001-CL301 (NCT02377921) with a UX001-CL302 baseline measurement and at least one post-baseline measurement in UX001-CL302.
Arm/Group Title Ace-ER 6 g/Day (Parent Study Treatment: Ace-ER 6 g/Day) Ace-ER 6 g/Day (Parent Study Treatment: Placebo)
Hide Arm/Group Description:
4 tablets (500 mg Ace-ER each for 2 g per dose) orally 3 times per day in participants who took Ace-ER in study UX001-CL301 (NCT02377921)
4 tablets (500 mg Ace-ER each for 2 g per dose) orally 3 times per day in participants who took placebo in study UX001-CL301 (NCT02377921)
Overall Number of Participants Analyzed 44 43
Least Squares Mean (95% Confidence Interval)
Unit of Measure: score on a scale
Week 8
-0.12
(-0.66 to 0.42)
0.15
(-0.35 to 0.65)
Week 16
-0.30
(-0.87 to 0.27)
-0.12
(-0.72 to 0.49)
Week 24
-0.78
(-1.31 to -0.25)
-0.34
(-0.92 to 0.23)
Week 48
-0.73
(-1.43 to -0.03)
-0.45
(-1.67 to 0.77)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ace-ER 6 g/Day (Parent Study Treatment: Ace-ER 6 g/Day), Ace-ER 6 g/Day (Parent Study Treatment: Placebo)
Comments Week 8
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4721
Comments Baseline is fit into the model as a covariate.
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.27
Confidence Interval (2-Sided) 95%
-1.01 to 0.47
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ace-ER 6 g/Day (Parent Study Treatment: Ace-ER 6 g/Day), Ace-ER 6 g/Day (Parent Study Treatment: Placebo)
Comments Week 16
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6611
Comments Baseline is fit into the model as a covariate.
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.19
Confidence Interval (2-Sided) 95%
-1.02 to 0.64
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ace-ER 6 g/Day (Parent Study Treatment: Ace-ER 6 g/Day), Ace-ER 6 g/Day (Parent Study Treatment: Placebo)
Comments Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2760
Comments [Not Specified]
Method GEE model
Comments Baseline is fit into the model as a covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.44
Confidence Interval (2-Sided) 95%
-1.22 to 0.35
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Ace-ER 6 g/Day (Parent Study Treatment: Ace-ER 6 g/Day), Ace-ER 6 g/Day (Parent Study Treatment: Placebo)
Comments Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6977
Comments Baseline is fit into the model as a covariate.
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.28
Confidence Interval (2-Sided) 95%
-1.69 to 1.13
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline on the GNEM-FAS Upper Extremity Domain Score Over Time
Hide Description GNEM-FAS Expanded Version Upper Extremity subscale score has 9 items and ranges from 0 to 36 with higher scores representing more skilled, independent use of the arms during functional activity performance. Analyzed using a repeated measure GEE model, which includes the baseline value as a covariate.
Time Frame Baseline, Weeks 8, 16, 24, 48
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all participants in parent study UX001-CL301 (NCT02377921) with a UX001-CL302 baseline measurement and at least one post-baseline measurement in UX001-CL302.
Arm/Group Title Ace-ER 6 g/Day (Parent Study Treatment: Ace-ER 6 g/Day) Ace-ER 6 g/Day (Parent Study Treatment: Placebo)
Hide Arm/Group Description:
4 tablets (500 mg Ace-ER each for 2 g per dose) orally 3 times per day in participants who took Ace-ER in study UX001-CL301 (NCT02377921)
4 tablets (500 mg Ace-ER each for 2 g per dose) orally 3 times per day in participants who took placebo in study UX001-CL301 (NCT02377921)
Overall Number of Participants Analyzed 44 43
Least Squares Mean (95% Confidence Interval)
Unit of Measure: score on a scale
Week 8
0.68
(0.15 to 1.22)
-0.02
(-0.55 to 0.51)
Week 16
0.34
(-0.21 to 0.89)
-0.40
(-0.99 to 0.19)
Week 24
0.26
(-0.41 to 0.93)
-0.17
(-1.01 to 0.67)
Week 48
-0.82
(-2.16 to 0.51)
-0.48
(-1.03 to 0.07)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ace-ER 6 g/Day (Parent Study Treatment: Ace-ER 6 g/Day), Ace-ER 6 g/Day (Parent Study Treatment: Placebo)
Comments Week 8
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0648
Comments Baseline is fit into the model as a covariate.
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value 0.70
Confidence Interval (2-Sided) 95%
-0.04 to 1.45
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ace-ER 6 g/Day (Parent Study Treatment: Ace-ER 6 g/Day), Ace-ER 6 g/Day (Parent Study Treatment: Placebo)
Comments Week 16
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0692
Comments Baseline is fit into the model as a covariate.
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in LS means
Estimated Value 0.74
Confidence Interval (2-Sided) 95%
-0.06 to 1.55
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ace-ER 6 g/Day (Parent Study Treatment: Ace-ER 6 g/Day), Ace-ER 6 g/Day (Parent Study Treatment: Placebo)
Comments Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4317
Comments Baseline is fit into the model as a covariate.
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in LS means
Estimated Value 0.44
Confidence Interval (2-Sided) 95%
-0.65 to 1.52
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Ace-ER 6 g/Day (Parent Study Treatment: Ace-ER 6 g/Day), Ace-ER 6 g/Day (Parent Study Treatment: Placebo)
Comments Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6416
Comments Baseline is fit into the model as a covariate.
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in LS means
Estimated Value -0.34
Confidence Interval (2-Sided) 95%
-1.78 to 1.10
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline in HHD Lower Extremity Composite (LEC) Score Over Time
Hide Description Hand held dynamometry testing was used to measure strength. The maximum voluntary isometric contraction against a dynamometer was used to measure bilateral strength in the following muscle groups: shoulder abductors, wrist extensors and knee extensors. Specialized dynamometers for the measurement of grip and key pinch strength were also used. The total force (in kgf) for each was recorded. The LEC is derived from the sum of the average of the right and left total force (measured in kgf). Analyzed using a repeated measure GEE model, which includes the baseline value as a covariate.
Time Frame Baseline, Weeks 8, 16, 24, and 48
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all participants in parent study UX001-CL301 (NCT02377921) with a UX001-CL302 baseline measurement and at least one post-baseline measurement in UX001-CL302.
Arm/Group Title Ace-ER 6 g/Day (Parent Study Treatment: Ace-ER 6 g/Day) Ace-ER 6 g/Day (Parent Study Treatment: Placebo)
Hide Arm/Group Description:
4 tablets (500 mg Ace-ER each for 2 g per dose) orally 3 times per day in participants who took Ace-ER in study UX001-CL301 (NCT02377921)
4 tablets (500 mg Ace-ER each for 2 g per dose) orally 3 times per day in participants who took placebo in study UX001-CL301 (NCT02377921)
Overall Number of Participants Analyzed 44 43
Least Squares Mean (95% Confidence Interval)
Unit of Measure: kgf
Week 8
0.01
(-2.01 to 2.04)
-0.77
(-3.65 to 2.11)
Week 16
-1.63
(-3.95 to 0.34)
-0.98
(-3.77 to 1.81)
Week 24
-0.60
(-3.90 to 2.71)
-0.10
(-3.82 to 3.62)
Week 48
-0.32
(-4.02 to 3.39)
-4.47
(-7.45 to -1.49)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ace-ER 6 g/Day (Parent Study Treatment: Ace-ER 6 g/Day), Ace-ER 6 g/Day (Parent Study Treatment: Placebo)
Comments Week 8
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6546
Comments Baseline is fit into the model as a covariate.
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in LS means
Estimated Value 0.78
Confidence Interval (2-Sided) 95%
-2.65 to 4.22
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ace-ER 6 g/Day (Parent Study Treatment: Ace-ER 6 g/Day), Ace-ER 6 g/Day (Parent Study Treatment: Placebo)
Comments Week 16
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7054
Comments Baseline is fit into the model as a covariate.
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in LS means
Estimated Value -0.64
Confidence Interval (2-Sided) 95%
-3.97 to 2.69
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ace-ER 6 g/Day (Parent Study Treatment: Ace-ER 6 g/Day), Ace-ER 6 g/Day (Parent Study Treatment: Placebo)
Comments Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8441
Comments Baseline is fit into the model as a covariate.
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in LS means
Estimated Value -0.50
Confidence Interval (2-Sided) 95%
-5.45 to 4.45
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Ace-ER 6 g/Day (Parent Study Treatment: Ace-ER 6 g/Day), Ace-ER 6 g/Day (Parent Study Treatment: Placebo)
Comments Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0864
Comments Baseline is fit into the model as a covariate.
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in LS means
Estimated Value 4.15
Confidence Interval (2-Sided) 95%
-0.59 to 8.90
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Change From Baseline in the Number of Stands in the Sit-to-Stand Test Over Time
Hide Description Lower extremity function was assessed using a sit-to-stand test. The number of times the participant can rise from a seated to a standing position in a 30-second period was recorded. Analyzed using a repeated measure GEE model, which includes the baseline value as a covariate.
Time Frame Baseline, Weeks 8, 16, 24, and 48
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all participants in parent study UX001-CL301 (NCT02377921) with a UX001-CL302 baseline measurement and at least one post-baseline measurement in UX001-CL302.
Arm/Group Title Ace-ER 6 g/Day (Parent Study Treatment: Ace-ER 6 g/Day) Ace-ER 6 g/Day (Parent Study Treatment: Placebo)
Hide Arm/Group Description:
4 tablets (500 mg Ace-ER each for 2 g per dose) orally 3 times per day in participants who took Ace-ER in study UX001-CL301 (NCT02377921)
4 tablets (500 mg Ace-ER each for 2 g per dose) orally 3 times per day in participants who took placebo in study UX001-CL301 (NCT02377921)
Overall Number of Participants Analyzed 44 43
Least Squares Mean (95% Confidence Interval)
Unit of Measure: stands
Week 8
0.02
(-0.43 to 0.46)
-0.05
(-0.61 to 0.51)
Week 16
-0.04
(-0.49 to 0.40)
0.14
(-0.39 to 0.66)
Week 24
0.06
(-0.43 to 0.56)
-0.41
(-0.94 to 0.12)
Week 48
-0.39
(-1.36 to 0.57)
-0.36
(-1.11 to 0.39)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ace-ER 6 g/Day (Parent Study Treatment: Ace-ER 6 g/Day), Ace-ER 6 g/Day (Parent Study Treatment: Placebo)
Comments Week 8
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8603
Comments Baseline is fit into the model as a covariate.
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in LS means
Estimated Value 0.06
Confidence Interval (2-Sided) 95%
-0.65 to 0.78
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ace-ER 6 g/Day (Parent Study Treatment: Ace-ER 6 g/Day), Ace-ER 6 g/Day (Parent Study Treatment: Placebo)
Comments Week 16
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6154
Comments Baseline is fit into the model as a covariate.
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in LS means
Estimated Value -0.18
Confidence Interval (2-Sided) 95%
-0.86 to 0.51
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ace-ER 6 g/Day (Parent Study Treatment: Ace-ER 6 g/Day), Ace-ER 6 g/Day (Parent Study Treatment: Placebo)
Comments Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1999
Comments Baseline is fit into the model as a covariate.
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in LS means
Estimated Value 0.47
Confidence Interval (2-Sided) 95%
-0.25 to 1.20
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Ace-ER 6 g/Day (Parent Study Treatment: Ace-ER 6 g/Day), Ace-ER 6 g/Day (Parent Study Treatment: Placebo)
Comments Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9568
Comments Baseline is fit into the model as a covariate.
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in LS means
Estimated Value -0.03
Confidence Interval (2-Sided) 95%
-1.25 to 1.18
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Change From Baseline in Number of Lifts in the 30-Second Weighted Arm Lift Test Over Time
Hide Description Upper extremity function was assessed using a weighted arm lift test performed bilaterally. The number of times the participant can raise a 1 kg weight above the head in a 30-second period was recorded. Analyzed using a repeated measure GEE model, which includes the baseline value as a covariate.
Time Frame Baseline, Weeks 8, 16, 24, and 48
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all participants in parent study UX001-CL301 (NCT02377921) with a UX001-CL302 baseline measurement and at least one post-baseline measurement in UX001-CL302.
Arm/Group Title Ace-ER 6 g/Day (Parent Study Treatment: Ace-ER 6 g/Day) Ace-ER 6 g/Day (Parent Study Treatment: Placebo)
Hide Arm/Group Description:
4 tablets (500 mg Ace-ER each for 2 g per dose) orally 3 times per day in participants who took Ace-ER in study UX001-CL301 (NCT02377921)
4 tablets (500 mg Ace-ER each for 2 g per dose) orally 3 times per day in participants who took placebo in study UX001-CL301 (NCT02377921)
Overall Number of Participants Analyzed 44 43
Least Squares Mean (95% Confidence Interval)
Unit of Measure: lifts
Week 8
0.26
(-1.00 to 1.52)
-0.19
(-0.90 to 0.53)
Week 16
0.03
(-1.22 to 1.27)
0.59
(-0.50 to 1.68)
Week 24
0.13
(-0.98 to 1.24)
-0.14
(-1.33 to 1.06)
Week 48
-1.58
(-3.60 to 0.45)
-1.17
(-2.55 to 0.22)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ace-ER 6 g/Day (Parent Study Treatment: Ace-ER 6 g/Day), Ace-ER 6 g/Day (Parent Study Treatment: Placebo)
Comments Week 8
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5447
Comments Baseline is fit into the model as a covariate.
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in LS means
Estimated Value 0.45
Confidence Interval (2-Sided) 95%
-1.00 to 1.90
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ace-ER 6 g/Day (Parent Study Treatment: Ace-ER 6 g/Day), Ace-ER 6 g/Day (Parent Study Treatment: Placebo)
Comments Week 16
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5051
Comments Baseline is fit into the model as a covariate.
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in LS means
Estimated Value -0.56
Confidence Interval (2-Sided) 95%
-2.22 to 1.09
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ace-ER 6 g/Day (Parent Study Treatment: Ace-ER 6 g/Day), Ace-ER 6 g/Day (Parent Study Treatment: Placebo)
Comments Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7478
Comments Baseline is fit into the model as a covariate.
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in LS means
Estimated Value 0.27
Confidence Interval (2-Sided) 95%
-1.36 to 1.90
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Ace-ER 6 g/Day (Parent Study Treatment: Ace-ER 6 g/Day), Ace-ER 6 g/Day (Parent Study Treatment: Placebo)
Comments Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7429
Comments Baseline is fit into the model as a covariate.
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in LS means
Estimated Value -0.41
Confidence Interval (2-Sided) 95%
-2.86 to 2.04
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Change From Baseline in Meters Walked in 6MWT Over Time
Hide Description The total distance walked (meters) in a 6-minute period was measured. Analyzed using a repeated measure GEE model, which includes the baseline value as a covariate.
Time Frame Baseline, Weeks 8, 16, 24, and 48
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all participants in parent study UX001-CL301 (NCT02377921) with a UX001-CL302 baseline measurement and at least one post-baseline measurement in UX001-CL302.
Arm/Group Title Ace-ER 6 g/Day (Parent Study Treatment: Ace-ER 6 g/Day) Ace-ER 6 g/Day (Parent Study Treatment: Placebo)
Hide Arm/Group Description:
4 tablets (500 mg Ace-ER each for 2 g per dose) orally 3 times per day in participants who took Ace-ER in study UX001-CL301 (NCT02377921)
4 tablets (500 mg Ace-ER each for 2 g per dose) orally 3 times per day in participants who took placebo in study UX001-CL301 (NCT02377921)
Overall Number of Participants Analyzed 44 43
Least Squares Mean (95% Confidence Interval)
Unit of Measure: meters
Week 8
-1.40
(-8.34 to 5.53)
-3.41
(-7.92 to 1.10)
Week 16
-3.91
(-12.03 to 4.20)
-1.93
(-8.32 to 4.47)
Week 24
-2.73
(-10.81 to 5.35)
-6.88
(-13.43 to -0.33)
Week 48
-13.91
(-25.58 to -2.25)
-21.89
(-38.51 to -5.28)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ace-ER 6 g/Day (Parent Study Treatment: Ace-ER 6 g/Day), Ace-ER 6 g/Day (Parent Study Treatment: Placebo)
Comments Week 8
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6434
Comments Baseline is fit into the model as a covariate.
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in LS means
Estimated Value 2.00
Confidence Interval (2-Sided) 95%
-6.48 to 10.49
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ace-ER 6 g/Day (Parent Study Treatment: Ace-ER 6 g/Day), Ace-ER 6 g/Day (Parent Study Treatment: Placebo)
Comments Week 16
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7118
Comments Baseline is fit into the model as a covariate.
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in LS means
Estimated Value -1.99
Confidence Interval (2-Sided) 95%
-12.53 to 8.55
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ace-ER 6 g/Day (Parent Study Treatment: Ace-ER 6 g/Day), Ace-ER 6 g/Day (Parent Study Treatment: Placebo)
Comments Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4399
Comments Baseline is fit into the model as a covariate.
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in LS means
Estimated Value 4.15
Confidence Interval (2-Sided) 95%
-6.39 to 14.69
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Ace-ER 6 g/Day (Parent Study Treatment: Ace-ER 6 g/Day), Ace-ER 6 g/Day (Parent Study Treatment: Placebo)
Comments Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4430
Comments Baseline is fit into the model as a covariate.
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in LS means
Estimated Value 7.98
Confidence Interval (2-Sided) 95%
-12.41 to 28.37
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Change From Baseline in Percent Predicted Meters Walked in 6MWT Over Time
Hide Description The total distance walked (meters) in a 6-minute period was measured, and the percent predicted distance based on normative data for age and gender was estimated. Predicted 6MWT distance (meters) = 868.8 - (2.99 x Age) - (74.7 x Sex), where age is baseline age in years, and sex = 0 for males, and 1 for females. Analyzed using a repeated measure GEE model, which includes the baseline value as a covariate.
Time Frame Baseline, Weeks 8, 16, 24, and 48
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all participants in parent study UX001-CL301 (NCT02377921) with a UX001-CL302 baseline measurement and at least one post-baseline measurement in UX001-CL302.
Arm/Group Title Ace-ER 6 g/Day (Parent Study Treatment: Ace-ER 6 g/Day) Ace-ER 6 g/Day (Parent Study Treatment: Placebo)
Hide Arm/Group Description:
4 tablets (500 mg Ace-ER each for 2 g per dose) orally 3 times per day in participants who took Ace-ER in study UX001-CL301 (NCT02377921)
4 tablets (500 mg Ace-ER each for 2 g per dose) orally 3 times per day in participants who took placebo in study UX001-CL301 (NCT02377921)
Overall Number of Participants Analyzed 44 43
Least Squares Mean (95% Confidence Interval)
Unit of Measure: percent of predicted distance
Week 8
-0.17
(-1.12 to 0.79)
-0.45
(-1.09 to 0.20)
Week 16
-0.49
(-1.60 to 0.61)
-0.24
(-1.15 to 0.67)
Week 24
-0.38
(-1.49 to 0.73)
-0.96
(-1.88 to -0.03)
Week 48
-1.94
(-3.56 to -0.31)
-2.93
(-5.04 to -0.81)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ace-ER 6 g/Day (Parent Study Treatment: Ace-ER 6 g/Day), Ace-ER 6 g/Day (Parent Study Treatment: Placebo)
Comments Week 8
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6428
Comments Baseline is fit into the model as a covariate.
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in LS means
Estimated Value 0.28
Confidence Interval (2-Sided) 95%
-0.90 to 1.46
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ace-ER 6 g/Day (Parent Study Treatment: Ace-ER 6 g/Day), Ace-ER 6 g/Day (Parent Study Treatment: Placebo)
Comments Week 16
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7334
Comments Baseline is fit into the model as a covariate.
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in LS means
Estimated Value -0.25
Confidence Interval (2-Sided) 95%
-1.72 to 1.21
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ace-ER 6 g/Day (Parent Study Treatment: Ace-ER 6 g/Day), Ace-ER 6 g/Day (Parent Study Treatment: Placebo)
Comments Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4409
Comments Baseline is fit into the model as a covariate.
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in LS means
Estimated Value 0.58
Confidence Interval (2-Sided) 95%
-0.89 to 2.04
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Ace-ER 6 g/Day (Parent Study Treatment: Ace-ER 6 g/Day), Ace-ER 6 g/Day (Parent Study Treatment: Placebo)
Comments Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4687
Comments Baseline is fit into the model as a covariate.
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in LS means
Estimated Value 0.99
Confidence Interval (2-Sided) 95%
-1.69 to 3.68
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Change From Baseline in Total Force in Knee Extensors Over Time
Hide Description Hand held dynamometry testing was used to measure strength. The maximum voluntary isometric contraction against a dynamometer was used to measure bilateral strength in the following muscle groups: shoulder abductors, wrist extensors and knee extensors. Specialized dynamometers for the measurement of grip and key pinch strength were also used. The total force (in kgf) for each was recorded. Bilateral total force was defined as the average of the right and left force (measured in kgf). Analyzed using a repeated measure GEE model, which includes the baseline value as a covariate.
Time Frame Baseline, Weeks 8, 16, 24, and 48
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all participants in parent study UX001-CL301 (NCT02377921) with a UX001-CL302 baseline measurement and at least one post-baseline measurement in UX001-CL302.
Arm/Group Title Ace-ER 6 g/Day (Parent Study Treatment: Ace-ER 6 g/Day) Ace-ER 6 g/Day (Parent Study Treatment: Placebo)
Hide Arm/Group Description:
4 tablets (500 mg Ace-ER each for 2 g per dose) orally 3 times per day in participants who took Ace-ER in study UX001-CL301 (NCT02377921)
4 tablets (500 mg Ace-ER each for 2 g per dose) orally 3 times per day in participants who took placebo in study UX001-CL301 (NCT02377921)
Overall Number of Participants Analyzed 44 43
Least Squares Mean (95% Confidence Interval)
Unit of Measure: kgf
Week 8
0.50
(-0.77 to 1.78)
-0.64
(-1.53 to 0.25)
Week 16
-0.95
(-2.03 to 0.14)
-0.75
(-2.05 to 0.55)
Week 24
0.33
(-1.33 to 2.00)
-0.46
(-2.15 to 1.23)
Week 48
0.63
(-2.30 to 3.56)
-0.08
(-2.28 to 2.13)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ace-ER 6 g/Day (Parent Study Treatment: Ace-ER 6 g/Day), Ace-ER 6 g/Day (Parent Study Treatment: Placebo)
Comments Week 8
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1502
Comments Baseline is fit into the model as a covariate.
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in LS means
Estimated Value 1.14
Confidence Interval (2-Sided) 95%
-0.41 to 2.69
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ace-ER 6 g/Day (Parent Study Treatment: Ace-ER 6 g/Day), Ace-ER 6 g/Day (Parent Study Treatment: Placebo)
Comments Week 16
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8188
Comments Baseline is fit into the model as a covariate.
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in LS means
Estimated Value -0.20
Confidence Interval (2-Sided) -1.89%
-1.89 to 1.49
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ace-ER 6 g/Day (Parent Study Treatment: Ace-ER 6 g/Day), Ace-ER 6 g/Day (Parent Study Treatment: Placebo)
Comments Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5122
Comments Baseline is fit into the model as a covariate.
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in LS means
Estimated Value 0.80
Confidence Interval (2-Sided) 95%
-1.58 to 3.17
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Ace-ER 6 g/Day (Parent Study Treatment: Ace-ER 6 g/Day), Ace-ER 6 g/Day (Parent Study Treatment: Placebo)
Comments Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7022
Comments Baseline is fit into the model as a covariate.
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in LS means
Estimated Value 0.72
Confidence Interval (2-Sided) 95%
-2.96 to 4.40
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Change From Baseline in Percent Predicted Total Force in Knee Extensors Over Time
Hide Description The percent predicted total force value of lower extremity muscle strength in the knee extensors was determined based on reference equations adjusting for age, gender, height, and weight. Analyzed using a repeated measure GEE model, which includes the baseline value as a covariate.
Time Frame Baseline, Weeks 8, 16, 24, and 48
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all participants in parent study UX001-CL301 (NCT02377921) with a UX001-CL302 baseline measurement and at least one post-baseline measurement in UX001-CL302.
Arm/Group Title Ace-ER 6 g/Day (Parent Study Treatment: Ace-ER 6 g/Day) Ace-ER 6 g/Day (Parent Study Treatment: Placebo)
Hide Arm/Group Description:
4 tablets (500 mg Ace-ER each for 2 g per dose) orally 3 times per day in participants who took Ace-ER in study UX001-CL301 (NCT02377921)
4 tablets (500 mg Ace-ER each for 2 g per dose) orally 3 times per day in participants who took placebo in study UX001-CL301 (NCT02377921)
Overall Number of Participants Analyzed 44 43
Least Squares Mean (95% Confidence Interval)
Unit of Measure: percent of predicted total force (kgf)
Week 8
-0.98
(-1.78 to -0.19)
-1.17
(-2.44 to 0.09)
Week 16
-0.59
(-1.48 to 0.31)
-1.25
(-2.43 to -0.07)
Week 24
-0.70
(-1.92 to 0.53)
-0.85
(-2.53 to 0.83)
Week 48
-1.02
(-2.17 to 0.13)
-3.10
(-4.40 to -1.80)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ace-ER 6 g/Day (Parent Study Treatment: Ace-ER 6 g/Day), Ace-ER 6 g/Day (Parent Study Treatment: Placebo)
Comments Week 8
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7906
Comments Baseline is fit into the model as a covariate.
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in LS means
Estimated Value 0.19
Confidence Interval (2-Sided) 95%
-1.22 to 1.60
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ace-ER 6 g/Day (Parent Study Treatment: Ace-ER 6 g/Day), Ace-ER 6 g/Day (Parent Study Treatment: Placebo)
Comments Week 16
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3531
Comments Baseline is fit into the model as a covariate.
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in LS means
Estimated Value 0.66
Confidence Interval (2-Sided) 95%
-0.74 to 2.07
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ace-ER 6 g/Day (Parent Study Treatment: Ace-ER 6 g/Day), Ace-ER 6 g/Day (Parent Study Treatment: Placebo)
Comments Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8846
Comments Baseline is fit into the model as a covariate.
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in LS means
Estimated Value 0.15
Confidence Interval (2-Sided) 95%
-1.92 to 2.23
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Ace-ER 6 g/Day (Parent Study Treatment: Ace-ER 6 g/Day), Ace-ER 6 g/Day (Parent Study Treatment: Placebo)
Comments Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0168
Comments Baseline is fit into the model as a covariate.
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in LS means
Estimated Value 2.08
Confidence Interval (2-Sided) 95%
0.38 to 3.79
Estimation Comments [Not Specified]
Time Frame From first dose of study drug through the end of treatment plus 30 days (+5 days). Mean (SD) duration of treatment was 256.3 (101.54) days.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Ace-ER 6 g/Day
Hide Arm/Group Description 4 tablets (500 mg Ace-ER each for 2 g per dose) orally 3 times per day
All-Cause Mortality
Ace-ER 6 g/Day
Affected / at Risk (%)
Total   0/142 (0.00%) 
Hide Serious Adverse Events
Ace-ER 6 g/Day
Affected / at Risk (%)
Total   7/142 (4.93%) 
Gastrointestinal disorders   
Abdominal pain  1  1/142 (0.70%) 
Hepatobiliary disorders   
Cholecystitis acute  1  1/142 (0.70%) 
Infections and infestations   
Atypical pneumonia  1  1/142 (0.70%) 
Investigations   
Biopsy kidney  1  1/142 (0.70%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Invasive ductal breast carcinoma  1  1/142 (0.70%) 
Malignant melanoma in situ  1  1/142 (0.70%) 
Renal and urinary disorders   
Renal pain  1  1/142 (0.70%) 
1
Term from vocabulary, MedDRA 17.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Ace-ER 6 g/Day
Affected / at Risk (%)
Total   66/142 (46.48%) 
Gastrointestinal disorders   
Diarrhoea  1  10/142 (7.04%) 
Flatulence  1  9/142 (6.34%) 
General disorders   
Fatigue  1  8/142 (5.63%) 
Infections and infestations   
Nasopharyngitis  1  8/142 (5.63%) 
Injury, poisoning and procedural complications   
Fall  1  30/142 (21.13%) 
Musculoskeletal and connective tissue disorders   
Arthralgia  1  17/142 (11.97%) 
Back pain  1  13/142 (9.15%) 
Musculoskeletal pain  1  11/142 (7.75%) 
Pain in extremity  1  10/142 (7.04%) 
Nervous system disorders   
Headache  1  8/142 (5.63%) 
1
Term from vocabulary, MedDRA 17.1
Indicates events were collected by systematic assessment
No efficacy result summaries or analyses were performed for participants rolling over from UX001-CL202 or UX001-CL203 because of the limited data from those participants due to the early study closure.
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.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Information
Organization: Ultragenyx Pharmaceutical Inc
Phone: 1-888-756-8657
EMail: medinfo@ultragenyx.com
Layout table for additonal information
Responsible Party: Ultragenyx Pharmaceutical Inc
ClinicalTrials.gov Identifier: NCT02736188    
Other Study ID Numbers: UX001-CL302
First Submitted: April 4, 2016
First Posted: April 13, 2016
Results First Submitted: January 7, 2019
Results First Posted: February 19, 2019
Last Update Posted: February 19, 2019