Trial Outcomes & Findings for 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) (NCT NCT02736188)
NCT ID: NCT02736188
Last Updated: 2023-03-24
Results Overview
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.
TERMINATED
PHASE3
143 participants
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.
2023-03-24
Participant Flow
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).
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.
Participant milestones
| Measure |
Ace-ER 6 g/Day
4 tablets (500 mg Ace-ER each for 2 g per dose) orally 3 times per day
|
|---|---|
|
Overall Study
STARTED
|
142
|
|
Overall Study
COMPLETED
|
0
|
|
Overall Study
NOT COMPLETED
|
142
|
Reasons for withdrawal
| Measure |
Ace-ER 6 g/Day
4 tablets (500 mg Ace-ER each for 2 g per dose) orally 3 times per day
|
|---|---|
|
Overall Study
Discontinuation of Study by Sponsor
|
134
|
|
Overall Study
Adverse Event
|
1
|
|
Overall Study
Withdrawal by Subject
|
1
|
|
Overall Study
Other
|
6
|
Baseline Characteristics
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.
Baseline characteristics by cohort
| Measure |
Ace-ER 6 g/Day
n=142 Participants
4 tablets (500 mg Ace-ER each for 2 g per dose) orally 3 times per day
|
|---|---|
|
Age, Continuous
|
74 years
STANDARD_DEVIATION 68 • n=142 Participants
|
|
Sex: Female, Male
Female
|
74 Participants
n=142 Participants
|
|
Sex: Female, Male
Male
|
68 Participants
n=142 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
14 Participants
n=142 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
125 Participants
n=142 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
3 Participants
n=142 Participants
|
|
Race/Ethnicity, Customized
White
|
111 Participants
n=142 Participants
|
|
Race/Ethnicity, Customized
Asian
|
19 Participants
n=142 Participants
|
|
Race/Ethnicity, Customized
Other, Not Specified
|
12 Participants
n=142 Participants
|
|
Hand Held Dynamometry (HHD) Upper Extremity Composite Score (UEC)
|
52.98 kgf
STANDARD_DEVIATION 28.814 • n=87 Participants • 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
|
24.17 score on a scale
STANDARD_DEVIATION 7.772 • n=87 Participants • 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
|
27.53 score on a scale
STANDARD_DEVIATION 4.938 • n=87 Participants • 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
|
51.91 kgf
STANDARD_DEVIATION 37.474 • n=86 Participants • 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
|
12.75 stands
STANDARD_DEVIATION 4.977 • n=87 Participants • 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
|
30.93 lifts
STANDARD_DEVIATION 13.171 • n=72 Participants • 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)
|
359.4 meters
STANDARD_DEVIATION 123.94 • n=83 Participants • 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
|
49.52 percentage of predicted meters
STANDARD_DEVIATION 16.962 • n=83 Participants • 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
|
26.60 kgf
STANDARD_DEVIATION 9.746 • n=84 Participants • 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
|
13.69 percent of predicted total force
STANDARD_DEVIATION 15.323 • n=81 Participants • 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.
|
PRIMARY outcome
Timeframe: 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.Population: Safety Analysis Set: all participants who received at least one dose of study drug in UX001-CL302.
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.
Outcome measures
| Measure |
Ace-ER 6 g/Day
n=142 Participants
4 tablets (500 mg Ace-ER each for 2 g per dose) orally 3 times per day
|
Ace-ER 6 g/Day (Parent Study Treatment: Placebo)
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)
|
|---|---|---|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious AEs (SAEs), and Discontinuations Due to AEs
TEAEs
|
104 Participants
|
—
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious AEs (SAEs), and Discontinuations Due to AEs
Serious TEAEs (SAEs)
|
7 Participants
|
—
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious AEs (SAEs), and Discontinuations Due to AEs
Deaths
|
0 Participants
|
—
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious AEs (SAEs), and Discontinuations Due to AEs
Grade 3 or 4 TEAEs
|
11 Participants
|
—
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious AEs (SAEs), and Discontinuations Due to AEs
TEAEs Leading to Study Drug Discontinuation
|
2 Participants
|
—
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious AEs (SAEs), and Discontinuations Due to AEs
TEAEs Leading to Study Discontinuation
|
1 Participants
|
—
|
PRIMARY outcome
Timeframe: Baseline, Weeks 8, 16, 24, 48Population: 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.
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.
Outcome measures
| Measure |
Ace-ER 6 g/Day
n=44 Participants
4 tablets (500 mg Ace-ER each for 2 g per dose) orally 3 times per day
|
Ace-ER 6 g/Day (Parent Study Treatment: Placebo)
n=43 Participants
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)
|
|---|---|---|
|
Change From Baseline in HHD UEC Score Over Time
Week 8
|
0.88 kgf
Interval -0.75 to 2.51
|
0.09 kgf
Interval -1.05 to 1.23
|
|
Change From Baseline in HHD UEC Score Over Time
Week 16
|
0.10 kgf
Interval -1.47 to 1.67
|
-0.26 kgf
Interval -1.26 to 0.74
|
|
Change From Baseline in HHD UEC Score Over Time
Week 24
|
-1.40 kgf
Interval -2.92 to 0.12
|
-0.49 kgf
Interval -2.13 to 1.15
|
|
Change From Baseline in HHD UEC Score Over Time
Week 48
|
-2.24 kgf
Interval -4.95 to 0.47
|
-2.18 kgf
Interval -4.3 to -0.07
|
SECONDARY outcome
Timeframe: Baseline, Weeks 8, 16, 24, 48Population: 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 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.
Outcome measures
| Measure |
Ace-ER 6 g/Day
n=44 Participants
4 tablets (500 mg Ace-ER each for 2 g per dose) orally 3 times per day
|
Ace-ER 6 g/Day (Parent Study Treatment: Placebo)
n=43 Participants
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)
|
|---|---|---|
|
Change From Baseline in the GNEM-FAS Expanded Version Mobility Domain Score Over Time
Week 8
|
-0.12 score on a scale
Interval -0.66 to 0.42
|
0.15 score on a scale
Interval -0.35 to 0.65
|
|
Change From Baseline in the GNEM-FAS Expanded Version Mobility Domain Score Over Time
Week 16
|
-0.30 score on a scale
Interval -0.87 to 0.27
|
-0.12 score on a scale
Interval -0.72 to 0.49
|
|
Change From Baseline in the GNEM-FAS Expanded Version Mobility Domain Score Over Time
Week 24
|
-0.78 score on a scale
Interval -1.31 to -0.25
|
-0.34 score on a scale
Interval -0.92 to 0.23
|
|
Change From Baseline in the GNEM-FAS Expanded Version Mobility Domain Score Over Time
Week 48
|
-0.73 score on a scale
Interval -1.43 to -0.03
|
-0.45 score on a scale
Interval -1.67 to 0.77
|
SECONDARY outcome
Timeframe: Baseline, Weeks 8, 16, 24, 48Population: 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 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.
Outcome measures
| Measure |
Ace-ER 6 g/Day
n=44 Participants
4 tablets (500 mg Ace-ER each for 2 g per dose) orally 3 times per day
|
Ace-ER 6 g/Day (Parent Study Treatment: Placebo)
n=43 Participants
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)
|
|---|---|---|
|
Change From Baseline on the GNEM-FAS Upper Extremity Domain Score Over Time
Week 8
|
0.68 score on a scale
Interval 0.15 to 1.22
|
-0.02 score on a scale
Interval -0.55 to 0.51
|
|
Change From Baseline on the GNEM-FAS Upper Extremity Domain Score Over Time
Week 16
|
0.34 score on a scale
Interval -0.21 to 0.89
|
-0.40 score on a scale
Interval -0.99 to 0.19
|
|
Change From Baseline on the GNEM-FAS Upper Extremity Domain Score Over Time
Week 24
|
0.26 score on a scale
Interval -0.41 to 0.93
|
-0.17 score on a scale
Interval -1.01 to 0.67
|
|
Change From Baseline on the GNEM-FAS Upper Extremity Domain Score Over Time
Week 48
|
-0.82 score on a scale
Interval -2.16 to 0.51
|
-0.48 score on a scale
Interval -1.03 to 0.07
|
SECONDARY outcome
Timeframe: Baseline, Weeks 8, 16, 24, and 48Population: 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.
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.
Outcome measures
| Measure |
Ace-ER 6 g/Day
n=44 Participants
4 tablets (500 mg Ace-ER each for 2 g per dose) orally 3 times per day
|
Ace-ER 6 g/Day (Parent Study Treatment: Placebo)
n=43 Participants
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)
|
|---|---|---|
|
Change From Baseline in HHD Lower Extremity Composite (LEC) Score Over Time
Week 8
|
0.01 kgf
Interval -2.01 to 2.04
|
-0.77 kgf
Interval -3.65 to 2.11
|
|
Change From Baseline in HHD Lower Extremity Composite (LEC) Score Over Time
Week 16
|
-1.63 kgf
Interval -3.95 to 0.34
|
-0.98 kgf
Interval -3.77 to 1.81
|
|
Change From Baseline in HHD Lower Extremity Composite (LEC) Score Over Time
Week 24
|
-0.60 kgf
Interval -3.9 to 2.71
|
-0.10 kgf
Interval -3.82 to 3.62
|
|
Change From Baseline in HHD Lower Extremity Composite (LEC) Score Over Time
Week 48
|
-0.32 kgf
Interval -4.02 to 3.39
|
-4.47 kgf
Interval -7.45 to -1.49
|
SECONDARY outcome
Timeframe: Baseline, Weeks 8, 16, 24, and 48Population: 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.
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.
Outcome measures
| Measure |
Ace-ER 6 g/Day
n=44 Participants
4 tablets (500 mg Ace-ER each for 2 g per dose) orally 3 times per day
|
Ace-ER 6 g/Day (Parent Study Treatment: Placebo)
n=43 Participants
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)
|
|---|---|---|
|
Change From Baseline in the Number of Stands in the Sit-to-Stand Test Over Time
Week 8
|
0.02 stands
Interval -0.43 to 0.46
|
-0.05 stands
Interval -0.61 to 0.51
|
|
Change From Baseline in the Number of Stands in the Sit-to-Stand Test Over Time
Week 16
|
-0.04 stands
Interval -0.49 to 0.4
|
0.14 stands
Interval -0.39 to 0.66
|
|
Change From Baseline in the Number of Stands in the Sit-to-Stand Test Over Time
Week 24
|
0.06 stands
Interval -0.43 to 0.56
|
-0.41 stands
Interval -0.94 to 0.12
|
|
Change From Baseline in the Number of Stands in the Sit-to-Stand Test Over Time
Week 48
|
-0.39 stands
Interval -1.36 to 0.57
|
-0.36 stands
Interval -1.11 to 0.39
|
SECONDARY outcome
Timeframe: Baseline, Weeks 8, 16, 24, and 48Population: 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.
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.
Outcome measures
| Measure |
Ace-ER 6 g/Day
n=44 Participants
4 tablets (500 mg Ace-ER each for 2 g per dose) orally 3 times per day
|
Ace-ER 6 g/Day (Parent Study Treatment: Placebo)
n=43 Participants
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)
|
|---|---|---|
|
Change From Baseline in Number of Lifts in the 30-Second Weighted Arm Lift Test Over Time
Week 8
|
0.26 lifts
Interval -1.0 to 1.52
|
-0.19 lifts
Interval -0.9 to 0.53
|
|
Change From Baseline in Number of Lifts in the 30-Second Weighted Arm Lift Test Over Time
Week 16
|
0.03 lifts
Interval -1.22 to 1.27
|
0.59 lifts
Interval -0.5 to 1.68
|
|
Change From Baseline in Number of Lifts in the 30-Second Weighted Arm Lift Test Over Time
Week 24
|
0.13 lifts
Interval -0.98 to 1.24
|
-0.14 lifts
Interval -1.33 to 1.06
|
|
Change From Baseline in Number of Lifts in the 30-Second Weighted Arm Lift Test Over Time
Week 48
|
-1.58 lifts
Interval -3.6 to 0.45
|
-1.17 lifts
Interval -2.55 to 0.22
|
SECONDARY outcome
Timeframe: Baseline, Weeks 8, 16, 24, and 48Population: 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.
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.
Outcome measures
| Measure |
Ace-ER 6 g/Day
n=44 Participants
4 tablets (500 mg Ace-ER each for 2 g per dose) orally 3 times per day
|
Ace-ER 6 g/Day (Parent Study Treatment: Placebo)
n=43 Participants
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)
|
|---|---|---|
|
Change From Baseline in Meters Walked in 6MWT Over Time
Week 24
|
-2.73 meters
Interval -10.81 to 5.35
|
-6.88 meters
Interval -13.43 to -0.33
|
|
Change From Baseline in Meters Walked in 6MWT Over Time
Week 8
|
-1.40 meters
Interval -8.34 to 5.53
|
-3.41 meters
Interval -7.92 to 1.1
|
|
Change From Baseline in Meters Walked in 6MWT Over Time
Week 16
|
-3.91 meters
Interval -12.03 to 4.2
|
-1.93 meters
Interval -8.32 to 4.47
|
|
Change From Baseline in Meters Walked in 6MWT Over Time
Week 48
|
-13.91 meters
Interval -25.58 to -2.25
|
-21.89 meters
Interval -38.51 to -5.28
|
SECONDARY outcome
Timeframe: Baseline, Weeks 8, 16, 24, and 48Population: 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.
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.
Outcome measures
| Measure |
Ace-ER 6 g/Day
n=44 Participants
4 tablets (500 mg Ace-ER each for 2 g per dose) orally 3 times per day
|
Ace-ER 6 g/Day (Parent Study Treatment: Placebo)
n=43 Participants
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)
|
|---|---|---|
|
Change From Baseline in Percent Predicted Meters Walked in 6MWT Over Time
Week 8
|
-0.17 percent of predicted distance
Interval -1.12 to 0.79
|
-0.45 percent of predicted distance
Interval -1.09 to 0.2
|
|
Change From Baseline in Percent Predicted Meters Walked in 6MWT Over Time
Week 16
|
-0.49 percent of predicted distance
Interval -1.6 to 0.61
|
-0.24 percent of predicted distance
Interval -1.15 to 0.67
|
|
Change From Baseline in Percent Predicted Meters Walked in 6MWT Over Time
Week 24
|
-0.38 percent of predicted distance
Interval -1.49 to 0.73
|
-0.96 percent of predicted distance
Interval -1.88 to -0.03
|
|
Change From Baseline in Percent Predicted Meters Walked in 6MWT Over Time
Week 48
|
-1.94 percent of predicted distance
Interval -3.56 to -0.31
|
-2.93 percent of predicted distance
Interval -5.04 to -0.81
|
SECONDARY outcome
Timeframe: Baseline, Weeks 8, 16, 24, and 48Population: 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.
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.
Outcome measures
| Measure |
Ace-ER 6 g/Day
n=44 Participants
4 tablets (500 mg Ace-ER each for 2 g per dose) orally 3 times per day
|
Ace-ER 6 g/Day (Parent Study Treatment: Placebo)
n=43 Participants
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)
|
|---|---|---|
|
Change From Baseline in Total Force in Knee Extensors Over Time
Week 8
|
0.50 kgf
Interval -0.77 to 1.78
|
-0.64 kgf
Interval -1.53 to 0.25
|
|
Change From Baseline in Total Force in Knee Extensors Over Time
Week 16
|
-0.95 kgf
Interval -2.03 to 0.14
|
-0.75 kgf
Interval -2.05 to 0.55
|
|
Change From Baseline in Total Force in Knee Extensors Over Time
Week 24
|
0.33 kgf
Interval -1.33 to 2.0
|
-0.46 kgf
Interval -2.15 to 1.23
|
|
Change From Baseline in Total Force in Knee Extensors Over Time
Week 48
|
0.63 kgf
Interval -2.3 to 3.56
|
-0.08 kgf
Interval -2.28 to 2.13
|
SECONDARY outcome
Timeframe: Baseline, Weeks 8, 16, 24, and 48Population: 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.
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.
Outcome measures
| Measure |
Ace-ER 6 g/Day
n=44 Participants
4 tablets (500 mg Ace-ER each for 2 g per dose) orally 3 times per day
|
Ace-ER 6 g/Day (Parent Study Treatment: Placebo)
n=43 Participants
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)
|
|---|---|---|
|
Change From Baseline in Percent Predicted Total Force in Knee Extensors Over Time
Week 8
|
-0.98 percent of predicted total force (kgf)
Interval -1.78 to -0.19
|
-1.17 percent of predicted total force (kgf)
Interval -2.44 to 0.09
|
|
Change From Baseline in Percent Predicted Total Force in Knee Extensors Over Time
Week 16
|
-0.59 percent of predicted total force (kgf)
Interval -1.48 to 0.31
|
-1.25 percent of predicted total force (kgf)
Interval -2.43 to -0.07
|
|
Change From Baseline in Percent Predicted Total Force in Knee Extensors Over Time
Week 24
|
-0.70 percent of predicted total force (kgf)
Interval -1.92 to 0.53
|
-0.85 percent of predicted total force (kgf)
Interval -2.53 to 0.83
|
|
Change From Baseline in Percent Predicted Total Force in Knee Extensors Over Time
Week 48
|
-1.02 percent of predicted total force (kgf)
Interval -2.17 to 0.13
|
-3.10 percent of predicted total force (kgf)
Interval -4.4 to -1.8
|
Adverse Events
Ace-ER 6 g/Day
Serious adverse events
| Measure |
Ace-ER 6 g/Day
n=142 participants at risk
4 tablets (500 mg Ace-ER each for 2 g per dose) orally 3 times per day
|
|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
0.70%
1/142 • 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.
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.70%
1/142 • 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.
|
|
Infections and infestations
Atypical pneumonia
|
0.70%
1/142 • 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.
|
|
Investigations
Biopsy kidney
|
0.70%
1/142 • 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.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Invasive ductal breast carcinoma
|
0.70%
1/142 • 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.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant melanoma in situ
|
0.70%
1/142 • 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.
|
|
Renal and urinary disorders
Renal pain
|
0.70%
1/142 • 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.
|
Other adverse events
| Measure |
Ace-ER 6 g/Day
n=142 participants at risk
4 tablets (500 mg Ace-ER each for 2 g per dose) orally 3 times per day
|
|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
7.0%
10/142 • 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.
|
|
Gastrointestinal disorders
Flatulence
|
6.3%
9/142 • 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.
|
|
General disorders
Fatigue
|
5.6%
8/142 • 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.
|
|
Infections and infestations
Nasopharyngitis
|
5.6%
8/142 • 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.
|
|
Injury, poisoning and procedural complications
Fall
|
21.1%
30/142 • 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.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
12.0%
17/142 • 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.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
9.2%
13/142 • 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.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
7.7%
11/142 • 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.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
7.0%
10/142 • 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.
|
|
Nervous system disorders
Headache
|
5.6%
8/142 • 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.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER