Trial Outcomes & Findings for Safety and Biomarker Study of EPI-589 in Participants With Amyotrophic Lateral Sclerosis (ALS) (NCT NCT02460679)
NCT ID: NCT02460679
Last Updated: 2020-10-14
Results Overview
An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and non-serious AEs. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the 'Reported AE section'.
COMPLETED
PHASE2
19 participants
Baseline (Day 0) to Month 6
2020-10-14
Participant Flow
Participant milestones
| Measure |
EPI-589
Participants received EPI-589 500 milligrams (mg) (2 tablets of 250 mg each) twice daily (BID) for 3 months, unless discontinued for safety or tolerability issues.
|
|---|---|
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Overall Study
STARTED
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19
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Overall Study
Received at Least 1 Dose of Study Drug
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19
|
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Overall Study
COMPLETED
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14
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Overall Study
NOT COMPLETED
|
5
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Reasons for withdrawal
| Measure |
EPI-589
Participants received EPI-589 500 milligrams (mg) (2 tablets of 250 mg each) twice daily (BID) for 3 months, unless discontinued for safety or tolerability issues.
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|---|---|
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Overall Study
Investigator Decision
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1
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Overall Study
Withdrawal by Subject
|
4
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Baseline Characteristics
'Number analyzed' signifies participants evaluable for specified categories.
Baseline characteristics by cohort
| Measure |
EPI-589
n=19 Participants
Participants received EPI-589 500 mg (2 tablets of 250 mg each) BID for 3 months, unless discontinued for safety or tolerability issues.
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|---|---|
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Age, Continuous
|
55.9 years
STANDARD_DEVIATION 8.25 • n=19 Participants
|
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Sex: Female, Male
Female
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5 Participants
n=19 Participants
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|
Sex: Female, Male
Male
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14 Participants
n=19 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
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2 Participants
n=19 Participants
|
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Ethnicity (NIH/OMB)
Not Hispanic or Latino
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17 Participants
n=19 Participants
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|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=19 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
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0 Participants
n=19 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=19 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=19 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=19 Participants
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|
Race (NIH/OMB)
White
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17 Participants
n=19 Participants
|
|
Race (NIH/OMB)
More than one race
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0 Participants
n=19 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=19 Participants
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|
Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) Score
|
37.4 units on a scale
STANDARD_DEVIATION 6.19 • n=19 Participants
|
|
Vital Capacity
|
97.7 percentage of capacity
STANDARD_DEVIATION 18.14 • n=19 Participants
|
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Maximum Inspiratory Pressure (MIP)
|
68.2 centimetres of water at (cm H2O)
STANDARD_DEVIATION 34.53 • n=19 Participants
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Respiratory Rate
Sitting
|
15.1 breaths/minute
STANDARD_DEVIATION 3.32 • n=19 Participants • 'Number analyzed' signifies participants evaluable for specified categories.
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Respiratory Rate
After 5 minutes supine
|
14.7 breaths/minute
STANDARD_DEVIATION 3.71 • n=13 Participants • 'Number analyzed' signifies participants evaluable for specified categories.
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Respiratory Rate
After 10 minutes supine
|
14.7 breaths/minute
STANDARD_DEVIATION 3.28 • n=15 Participants • 'Number analyzed' signifies participants evaluable for specified categories.
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|
Heart Rate
Sitting
|
68.9 beats/minute
STANDARD_DEVIATION 10.99 • n=19 Participants • 'Number analyzed' signifies participants evaluable for specified categories.
|
|
Heart Rate
After 5 minutes supine
|
63.8 beats/minute
STANDARD_DEVIATION 13.46 • n=13 Participants • 'Number analyzed' signifies participants evaluable for specified categories.
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|
Heart Rate
After 10 minutes supine
|
65.3 beats/minute
STANDARD_DEVIATION 12.30 • n=15 Participants • 'Number analyzed' signifies participants evaluable for specified categories.
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|
Oxygen Saturation (SpO2)
Sitting
|
96.9 percentage of hemoglobin
STANDARD_DEVIATION 1.65 • n=19 Participants • 'Number analyzed' signifies participants evaluable for specified categories.
|
|
Oxygen Saturation (SpO2)
After 5 minutes supine
|
95.4 percentage of hemoglobin
STANDARD_DEVIATION 2.79 • n=13 Participants • 'Number analyzed' signifies participants evaluable for specified categories.
|
|
Oxygen Saturation (SpO2)
After 10 minutes supine
|
95.1 percentage of hemoglobin
STANDARD_DEVIATION 2.70 • n=15 Participants • 'Number analyzed' signifies participants evaluable for specified categories.
|
|
End-Tidal Carbon Dioxide (ETCO2)
Sitting
|
24.833 percentage of CO2
STANDARD_DEVIATION 16.8444 • n=19 Participants • 'Number analyzed' signifies participants evaluable for specified categories.
|
|
End-Tidal Carbon Dioxide (ETCO2)
After 5 minutes supine
|
30.964 percentage of CO2
STANDARD_DEVIATION 15.9007 • n=13 Participants • 'Number analyzed' signifies participants evaluable for specified categories.
|
|
End-Tidal Carbon Dioxide (ETCO2)
After 10 minutes supine
|
31.186 percentage of CO2
STANDARD_DEVIATION 14.5895 • n=15 Participants • 'Number analyzed' signifies participants evaluable for specified categories.
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|
Average Solid Swallowing Time
|
12.46 seconds
STANDARD_DEVIATION 5.465 • n=19 Participants
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Average Water Swallowing Time
|
4.68 seconds
STANDARD_DEVIATION 3.698 • n=19 Participants
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Muscle Function, as Assessed by Handheld Dynamometry Parameters
Grip - Left
|
26.41 kilograms
STANDARD_DEVIATION 20.630 • n=17 Participants • 'Number analyzed' signifies participants evaluable for specified categories.
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|
Muscle Function, as Assessed by Handheld Dynamometry Parameters
Grip - Right
|
26.86 kilograms
STANDARD_DEVIATION 18.667 • n=18 Participants • 'Number analyzed' signifies participants evaluable for specified categories.
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|
Muscle Function, as Assessed by Handheld Dynamometry Parameters
Shoulder Flexion - Left
|
13.94 kilograms
STANDARD_DEVIATION 8.218 • n=17 Participants • 'Number analyzed' signifies participants evaluable for specified categories.
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|
Muscle Function, as Assessed by Handheld Dynamometry Parameters
Shoulder Flexion - Right
|
14.42 kilograms
STANDARD_DEVIATION 9.850 • n=17 Participants • 'Number analyzed' signifies participants evaluable for specified categories.
|
|
Muscle Function, as Assessed by Handheld Dynamometry Parameters
Knee Extension - Left
|
22.11 kilograms
STANDARD_DEVIATION 12.796 • n=19 Participants • 'Number analyzed' signifies participants evaluable for specified categories.
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|
Muscle Function, as Assessed by Handheld Dynamometry Parameters
Knee Extension - Right
|
22.13 kilograms
STANDARD_DEVIATION 13.224 • n=19 Participants • 'Number analyzed' signifies participants evaluable for specified categories.
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|
Muscle Function, as Assessed by Handheld Dynamometry Parameters
Knee Flexion - Left
|
17.32 kilograms
STANDARD_DEVIATION 11.832 • n=19 Participants • 'Number analyzed' signifies participants evaluable for specified categories.
|
|
Muscle Function, as Assessed by Handheld Dynamometry Parameters
Knee Flexion - Right
|
18.02 kilograms
STANDARD_DEVIATION 12.987 • n=19 Participants • 'Number analyzed' signifies participants evaluable for specified categories.
|
|
Muscle Function, as Assessed by Handheld Dynamometry Parameters
Hip Flexion - Left
|
20.13 kilograms
STANDARD_DEVIATION 16.229 • n=19 Participants • 'Number analyzed' signifies participants evaluable for specified categories.
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|
Muscle Function, as Assessed by Handheld Dynamometry Parameters
Hip Flexion - Right
|
20.82 kilograms
STANDARD_DEVIATION 12.738 • n=19 Participants • 'Number analyzed' signifies participants evaluable for specified categories.
|
|
Muscle Function, as Assessed by Handheld Dynamometry Parameters
Elbow Flexion - Left
|
17.16 kilograms
STANDARD_DEVIATION 9.074 • n=17 Participants • 'Number analyzed' signifies participants evaluable for specified categories.
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|
Muscle Function, as Assessed by Handheld Dynamometry Parameters
Elbow Flexion - Right
|
16.52 kilograms
STANDARD_DEVIATION 10.508 • n=17 Participants • 'Number analyzed' signifies participants evaluable for specified categories.
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|
Muscle Function, as Assessed by Handheld Dynamometry Parameters
Elbow Extension - Left
|
17.51 kilograms
STANDARD_DEVIATION 10.514 • n=17 Participants • 'Number analyzed' signifies participants evaluable for specified categories.
|
|
Muscle Function, as Assessed by Handheld Dynamometry Parameters
Elbow Extension - Right
|
15.36 kilograms
STANDARD_DEVIATION 10.482 • n=18 Participants • 'Number analyzed' signifies participants evaluable for specified categories.
|
|
Muscle Function, as Assessed by Handheld Dynamometry Parameters
Ankle Dorsi Flexion - Left
|
16.47 kilograms
STANDARD_DEVIATION 12.188 • n=18 Participants • 'Number analyzed' signifies participants evaluable for specified categories.
|
|
Muscle Function, as Assessed by Handheld Dynamometry Parameters
Ankle Dorsi Flexion - Right
|
13.04 kilograms
STANDARD_DEVIATION 10.898 • n=18 Participants • 'Number analyzed' signifies participants evaluable for specified categories.
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|
Number of Words Participant Read
|
100.3 Words
STANDARD_DEVIATION 0.45 • n=19 Participants
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|
Time Spent in Reading
|
48.5 seconds
STANDARD_DEVIATION 23.51 • n=19 Participants
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|
Number of Words Per Minute Read
|
143.529 words/minute
STANDARD_DEVIATION 45.4527 • n=19 Participants
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PRIMARY outcome
Timeframe: Baseline (Day 0) to Month 6Population: Safety population included any participant who received at least 1 dose of EPI-589.
An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and non-serious AEs. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the 'Reported AE section'.
Outcome measures
| Measure |
EPI-589
n=19 Participants
Participants received EPI-589 500 mg (2 tablets of 250 mg each) BID for 3 months, unless discontinued for safety or tolerability issues.
|
|---|---|
|
Number of Participants With Drug-Related Serious Adverse Events (SAEs)
|
0 Participants
|
SECONDARY outcome
Timeframe: Pre-dose (0 hour), 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose at Month 1 and 3Population: EITT population or safety population included any participant who received at least 1 dose of EPI-589. Here, 'Number analyzed' signifies participants evaluable at specified timepoints.
Outcome measures
| Measure |
EPI-589
n=19 Participants
Participants received EPI-589 500 mg (2 tablets of 250 mg each) BID for 3 months, unless discontinued for safety or tolerability issues.
|
|---|---|
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Area Under the Plasma Concentration Versus Time Curve From Time 0 to 12 Hours (AUC0-12)
Month 1
|
7762.7 hours*nanograms/milliliter
Standard Error 721.1
|
|
Area Under the Plasma Concentration Versus Time Curve From Time 0 to 12 Hours (AUC0-12)
Month 3
|
6878.8 hours*nanograms/milliliter
Standard Error 401.1
|
SECONDARY outcome
Timeframe: Pre-dose (0 hour), 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose at Month 1 and 3Population: EITT population or safety population included any participant who received at least 1 dose of EPI-589. Here, 'Number analyzed' signifies participants evaluable at specified timepoints.
Outcome measures
| Measure |
EPI-589
n=19 Participants
Participants received EPI-589 500 mg (2 tablets of 250 mg each) BID for 3 months, unless discontinued for safety or tolerability issues.
|
|---|---|
|
Maximum Observed Plasma Concentration (Cmax)
Month 1
|
5179.0 ng/mL
Standard Error 930.3
|
|
Maximum Observed Plasma Concentration (Cmax)
Month 3
|
4167.8 ng/mL
Standard Error 642.2
|
SECONDARY outcome
Timeframe: Baseline, Month 6Population: EITT population included any participant who received at least 1 dose of EPI-589. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.
ALSFRS-R is a quickly administered (5 minutes) ordinal rating scale that assesses participant's capability and independence in 12 functional activities. All 12 activities, 6 bulbar-respiratory functions, 3 upper extremity functions (writing, cutting food, and dressing), 2 lower-extremity functions (walking and climbing), and 1 other function (turning in bed), are relevant in ALS. Each activity was recorded to the closest approximation from a list of 5 choices, scored 0-4, with the total score ranging from 48 (normal function) to 0 (unable to attempt the task).
Outcome measures
| Measure |
EPI-589
n=14 Participants
Participants received EPI-589 500 mg (2 tablets of 250 mg each) BID for 3 months, unless discontinued for safety or tolerability issues.
|
|---|---|
|
Change From Baseline in ALSFRS-R Total Score at Month 6
|
-4.1 units on a scale
Standard Deviation 4.03
|
SECONDARY outcome
Timeframe: Baseline, Month 6Population: EITT population included any participant who received at least 1 dose of EPI-589. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.
Vital capacity is the maximum amount of air a participant can expel from the lungs after a maximum inhalation.
Outcome measures
| Measure |
EPI-589
n=14 Participants
Participants received EPI-589 500 mg (2 tablets of 250 mg each) BID for 3 months, unless discontinued for safety or tolerability issues.
|
|---|---|
|
Change From Baseline in Vital Capacity at Month 6
|
-3.1 percentage of capacity
Standard Deviation 9.36
|
SECONDARY outcome
Timeframe: Baseline, Month 6Population: EITT population included any participant who received at least 1 dose of EPI-589. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.
MIP is a measure of the strength of inspiratory muscles, primarily the diaphragm, and allows for the assessment of ventilatory failure, restrictive lung disease, and respiratory muscle strength.
Outcome measures
| Measure |
EPI-589
n=14 Participants
Participants received EPI-589 500 mg (2 tablets of 250 mg each) BID for 3 months, unless discontinued for safety or tolerability issues.
|
|---|---|
|
Change From Baseline in MIP at Month 6
|
2.4 cm H2O
Standard Deviation 24.83
|
SECONDARY outcome
Timeframe: Baseline, Month 6Population: EITT population included any participant who received at least 1 dose of EPI-589. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure. 'Number analyzed' signifies participants evaluable for specified categories.
Respiratory rate is the rate at which breathing occurs.
Outcome measures
| Measure |
EPI-589
n=14 Participants
Participants received EPI-589 500 mg (2 tablets of 250 mg each) BID for 3 months, unless discontinued for safety or tolerability issues.
|
|---|---|
|
Change From Baseline in Respiratory Rate at Month 6
Sitting
|
0.3 breaths/minute
Standard Deviation 3.45
|
|
Change From Baseline in Respiratory Rate at Month 6
After 5 minutes supine
|
-0.6 breaths/minute
Standard Deviation 5.57
|
|
Change From Baseline in Respiratory Rate at Month 6
After 10 minutes supine
|
0.0 breaths/minute
Standard Deviation 4.32
|
SECONDARY outcome
Timeframe: Baseline, Month 6Population: EITT population included any participant who received at least 1 dose of EPI-589. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure. 'Number analyzed' signifies participants evaluable for specified categories.
The heart rate measures the number of times the heart beats per minute.
Outcome measures
| Measure |
EPI-589
n=14 Participants
Participants received EPI-589 500 mg (2 tablets of 250 mg each) BID for 3 months, unless discontinued for safety or tolerability issues.
|
|---|---|
|
Change From Baseline in Heart Rate at Month 6
Sitting
|
5.2 beats/minute
Standard Deviation 10.74
|
|
Change From Baseline in Heart Rate at Month 6
After 5 minutes supine
|
7.1 beats/minute
Standard Deviation 7.49
|
|
Change From Baseline in Heart Rate at Month 6
After 10 minutes supine
|
7.2 beats/minute
Standard Deviation 8.39
|
SECONDARY outcome
Timeframe: Baseline, Month 6Population: EITT population included any participant who received at least 1 dose of EPI-589. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure. 'Number analyzed' signifies participants evaluable for specified categories.
SpO2, also known as oxygen saturation, is a measure of the amount of oxygen-carrying hemoglobin in the blood relative to the amount of hemoglobin not carrying oxygen.
Outcome measures
| Measure |
EPI-589
n=14 Participants
Participants received EPI-589 500 mg (2 tablets of 250 mg each) BID for 3 months, unless discontinued for safety or tolerability issues.
|
|---|---|
|
Change From Baseline in SpO2 at Month 6
Sitting
|
-1.0 percentage of hemoglobin
Standard Deviation 1.71
|
|
Change From Baseline in SpO2 at Month 6
After 5 minutes supine
|
-0.8 percentage of hemoglobin
Standard Deviation 4.64
|
|
Change From Baseline in SpO2 at Month 6
After 10 minutes supine
|
-0.1 percentage of hemoglobin
Standard Deviation 3.55
|
SECONDARY outcome
Timeframe: Baseline, Month 6Population: EITT population included any participant who received at least 1 dose of EPI-589. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure. 'Number analyzed' signifies participants evaluable for specified categories.
ETCO2 is the amount of CO2 in exhaled air, which assesses ventilation.
Outcome measures
| Measure |
EPI-589
n=14 Participants
Participants received EPI-589 500 mg (2 tablets of 250 mg each) BID for 3 months, unless discontinued for safety or tolerability issues.
|
|---|---|
|
Change From Baseline in ETCO2 at Month 6
Sitting
|
2.384 percentage of CO2
Standard Deviation 8.2343
|
|
Change From Baseline in ETCO2 at Month 6
After 5 minutes supine
|
0.605 percentage of CO2
Standard Deviation 5.0262
|
|
Change From Baseline in ETCO2 at Month 6
After 10 minutes supine
|
7.112 percentage of CO2
Standard Deviation 9.6591
|
SECONDARY outcome
Timeframe: Baseline, Month 6Population: EITT population included any participant who received at least 1 dose of EPI-589. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.
The failure to thrive as measured by body weight was defined as weight loss of more than 5% from baseline
Outcome measures
| Measure |
EPI-589
n=14 Participants
Participants received EPI-589 500 mg (2 tablets of 250 mg each) BID for 3 months, unless discontinued for safety or tolerability issues.
|
|---|---|
|
Failure to Thrive: Number of Participants With Weight Loss of More Than 5 Percent (%) From Baseline at Month 6
|
2 Participants
|
SECONDARY outcome
Timeframe: Baseline, Month 6Population: EITT population included any participant who received at least 1 dose of EPI-589. Here, 'Number analyzed' signifies participants evaluable for specified categories.
Participants were observed and timed swallowing water as well as solid foods in accordance with a standardized protocol.
Outcome measures
| Measure |
EPI-589
n=19 Participants
Participants received EPI-589 500 mg (2 tablets of 250 mg each) BID for 3 months, unless discontinued for safety or tolerability issues.
|
|---|---|
|
Change From Baseline in Average Solid Swallowing Time and Water Swallowing Time at Month 6
Average Solid Swallowing Time
|
4.80 seconds
Standard Deviation 11.718
|
|
Change From Baseline in Average Solid Swallowing Time and Water Swallowing Time at Month 6
Average Water Swallowing Time
|
6.65 seconds
Standard Deviation 20.950
|
SECONDARY outcome
Timeframe: Baseline, Month 6Population: EITT population included any participant who received at least 1 dose of EPI-589. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure. 'Number analyzed' signifies participants evaluable for specified categories.
The strength of designated muscle groups was measured using handheld dynamometry.
Outcome measures
| Measure |
EPI-589
n=14 Participants
Participants received EPI-589 500 mg (2 tablets of 250 mg each) BID for 3 months, unless discontinued for safety or tolerability issues.
|
|---|---|
|
Change From Baseline in Muscle Function at Month 6, as Assessed by Handheld Dynamometry Parameters (Grip Strength, Shoulder Flexion, Knee Extension, Hip Flexion, Elbow Flexion, Elbow Extension, and Ankle Dorsi Flexion)
Hip Flexion - Left
|
-6.84 kilograms
Standard Deviation 12.579
|
|
Change From Baseline in Muscle Function at Month 6, as Assessed by Handheld Dynamometry Parameters (Grip Strength, Shoulder Flexion, Knee Extension, Hip Flexion, Elbow Flexion, Elbow Extension, and Ankle Dorsi Flexion)
Grip - Left
|
-9.69 kilograms
Standard Deviation 15.330
|
|
Change From Baseline in Muscle Function at Month 6, as Assessed by Handheld Dynamometry Parameters (Grip Strength, Shoulder Flexion, Knee Extension, Hip Flexion, Elbow Flexion, Elbow Extension, and Ankle Dorsi Flexion)
Grip - Right
|
-7.28 kilograms
Standard Deviation 7.207
|
|
Change From Baseline in Muscle Function at Month 6, as Assessed by Handheld Dynamometry Parameters (Grip Strength, Shoulder Flexion, Knee Extension, Hip Flexion, Elbow Flexion, Elbow Extension, and Ankle Dorsi Flexion)
Shoulder Flexion - Left
|
-4.53 kilograms
Standard Deviation 6.922
|
|
Change From Baseline in Muscle Function at Month 6, as Assessed by Handheld Dynamometry Parameters (Grip Strength, Shoulder Flexion, Knee Extension, Hip Flexion, Elbow Flexion, Elbow Extension, and Ankle Dorsi Flexion)
Shoulder Flexion - Right
|
-5.43 kilograms
Standard Deviation 8.915
|
|
Change From Baseline in Muscle Function at Month 6, as Assessed by Handheld Dynamometry Parameters (Grip Strength, Shoulder Flexion, Knee Extension, Hip Flexion, Elbow Flexion, Elbow Extension, and Ankle Dorsi Flexion)
Knee Extension - Left
|
-5.42 kilograms
Standard Deviation 10.254
|
|
Change From Baseline in Muscle Function at Month 6, as Assessed by Handheld Dynamometry Parameters (Grip Strength, Shoulder Flexion, Knee Extension, Hip Flexion, Elbow Flexion, Elbow Extension, and Ankle Dorsi Flexion)
Knee Extension - Right
|
-5.05 kilograms
Standard Deviation 11.505
|
|
Change From Baseline in Muscle Function at Month 6, as Assessed by Handheld Dynamometry Parameters (Grip Strength, Shoulder Flexion, Knee Extension, Hip Flexion, Elbow Flexion, Elbow Extension, and Ankle Dorsi Flexion)
Knee Flexion - Left
|
-4.63 kilograms
Standard Deviation 8.237
|
|
Change From Baseline in Muscle Function at Month 6, as Assessed by Handheld Dynamometry Parameters (Grip Strength, Shoulder Flexion, Knee Extension, Hip Flexion, Elbow Flexion, Elbow Extension, and Ankle Dorsi Flexion)
Knee Flexion - Right
|
-4.01 kilograms
Standard Deviation 9.170
|
|
Change From Baseline in Muscle Function at Month 6, as Assessed by Handheld Dynamometry Parameters (Grip Strength, Shoulder Flexion, Knee Extension, Hip Flexion, Elbow Flexion, Elbow Extension, and Ankle Dorsi Flexion)
Hip Flexion - Right
|
-5.60 kilograms
Standard Deviation 9.627
|
|
Change From Baseline in Muscle Function at Month 6, as Assessed by Handheld Dynamometry Parameters (Grip Strength, Shoulder Flexion, Knee Extension, Hip Flexion, Elbow Flexion, Elbow Extension, and Ankle Dorsi Flexion)
Elbow Flexion - Left
|
-4.84 kilograms
Standard Deviation 8.377
|
|
Change From Baseline in Muscle Function at Month 6, as Assessed by Handheld Dynamometry Parameters (Grip Strength, Shoulder Flexion, Knee Extension, Hip Flexion, Elbow Flexion, Elbow Extension, and Ankle Dorsi Flexion)
Elbow Flexion - Right
|
-3.28 kilograms
Standard Deviation 8.186
|
|
Change From Baseline in Muscle Function at Month 6, as Assessed by Handheld Dynamometry Parameters (Grip Strength, Shoulder Flexion, Knee Extension, Hip Flexion, Elbow Flexion, Elbow Extension, and Ankle Dorsi Flexion)
Elbow Extension - Left
|
-5.77 kilograms
Standard Deviation 10.511
|
|
Change From Baseline in Muscle Function at Month 6, as Assessed by Handheld Dynamometry Parameters (Grip Strength, Shoulder Flexion, Knee Extension, Hip Flexion, Elbow Flexion, Elbow Extension, and Ankle Dorsi Flexion)
Elbow Extension - Right
|
-4.28 kilograms
Standard Deviation 9.048
|
|
Change From Baseline in Muscle Function at Month 6, as Assessed by Handheld Dynamometry Parameters (Grip Strength, Shoulder Flexion, Knee Extension, Hip Flexion, Elbow Flexion, Elbow Extension, and Ankle Dorsi Flexion)
Ankle Dorsi Flexion - Left
|
-6.12 kilograms
Standard Deviation 7.609
|
|
Change From Baseline in Muscle Function at Month 6, as Assessed by Handheld Dynamometry Parameters (Grip Strength, Shoulder Flexion, Knee Extension, Hip Flexion, Elbow Flexion, Elbow Extension, and Ankle Dorsi Flexion)
Ankle Dorsi Flexion - Right
|
-4.89 kilograms
Standard Deviation 7.529
|
SECONDARY outcome
Timeframe: Baseline, Month 6Population: EITT population included any participant who received at least 1 dose of EPI-589. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.
The participant performed tasks in which speech was assessed through a perceptual assessment of overall intelligibility, vocal quality, and other factors by a speech language pathologist.
Outcome measures
| Measure |
EPI-589
n=13 Participants
Participants received EPI-589 500 mg (2 tablets of 250 mg each) BID for 3 months, unless discontinued for safety or tolerability issues.
|
|---|---|
|
Change From Baseline in Number of Words Participant Read at Month 6
|
0.0 words
Standard Deviation 0.00
|
SECONDARY outcome
Timeframe: Baseline, Month 6Population: EITT population included any participant who received at least 1 dose of EPI-589. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.
The participant performed tasks in which speech was assessed through a perceptual assessment of overall intelligibility, vocal quality, and other factors by a speech language pathologist.
Outcome measures
| Measure |
EPI-589
n=13 Participants
Participants received EPI-589 500 mg (2 tablets of 250 mg each) BID for 3 months, unless discontinued for safety or tolerability issues.
|
|---|---|
|
Change From Baseline in Time Spent in Reading at Month 6
|
5.5 seconds
Standard Deviation 11.78
|
SECONDARY outcome
Timeframe: Baseline, Month 6Population: EITT population included any participant who received at least 1 dose of EPI-589. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.
The participant performed tasks in which speech was assessed through a perceptual assessment of overall intelligibility, vocal quality, and other factors by a speech language pathologist.
Outcome measures
| Measure |
EPI-589
n=13 Participants
Participants received EPI-589 500 mg (2 tablets of 250 mg each) BID for 3 months, unless discontinued for safety or tolerability issues.
|
|---|---|
|
Change From Baseline in Number of Words Per Minute Read at Month 6
|
-147.535 words/minute
Standard Deviation 26.7792
|
SECONDARY outcome
Timeframe: Month 6Population: EITT population included any participant who received at least 1 dose of EPI-589. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.
The participant performed tasks in which speech was assessed through a perceptual assessment of overall intelligibility, vocal quality, and other factors by a speech language pathologist.
Outcome measures
| Measure |
EPI-589
n=13 Participants
Participants received EPI-589 500 mg (2 tablets of 250 mg each) BID for 3 months, unless discontinued for safety or tolerability issues.
|
|---|---|
|
Number of Participants With Normal Loudness, Normal Nasality, and Normal Intelligibility
Normal Loudness
|
10 Participants
|
|
Number of Participants With Normal Loudness, Normal Nasality, and Normal Intelligibility
Normal Nasality
|
6 Participants
|
|
Number of Participants With Normal Loudness, Normal Nasality, and Normal Intelligibility
Normal Intelligibility
|
6 Participants
|
SECONDARY outcome
Timeframe: Baseline up to Month 6Population: EITT population included any participant who received at least 1 dose of EPI-589. Here, 'Overall number of participants analyzed' signifies participants with both baseline and Month 6 glutathione in plasma data.
Glutathione lowest limit of quantification (LLOQ) = 0.089 micromoles (uM) and upper limit of quantification (ULOQ) = 13.916 uM in plasma.
Outcome measures
| Measure |
EPI-589
n=15 Participants
Participants received EPI-589 500 mg (2 tablets of 250 mg each) BID for 3 months, unless discontinued for safety or tolerability issues.
|
|---|---|
|
Level of Disease-Related Biomarker (Glutathione) in Plasma
Baseline
|
1.34 µM
Interval 0.41 to 2.15
|
|
Level of Disease-Related Biomarker (Glutathione) in Plasma
Month 6
|
2.73 µM
Interval 0.83 to 11.74
|
SECONDARY outcome
Timeframe: Baseline up to Month 3Population: EITT population included any participant who received at least 1 dose of EPI-589. Here, 'Overall number of participants analyzed' signifies participants with both baseline and Month 3 glutathione in CSF data.
Glutathione LLOQ = 0.002 uM and ULOQ = 0.35 uM in CSF.
Outcome measures
| Measure |
EPI-589
n=10 Participants
Participants received EPI-589 500 mg (2 tablets of 250 mg each) BID for 3 months, unless discontinued for safety or tolerability issues.
|
|---|---|
|
Level of Disease-Related Biomarker (Glutathione) in Cerebrospinal Fluid (CSF)
Baseline
|
0.13 µM
Interval 0.04 to 0.31
|
|
Level of Disease-Related Biomarker (Glutathione) in Cerebrospinal Fluid (CSF)
Month 3
|
0.13 µM
Interval 0.06 to 0.31
|
SECONDARY outcome
Timeframe: Baseline up to Month 6Population: EITT population included any participant who received at least 1 dose of EPI-589. Here, 'Overall number of participants analyzed' signifies participants with both baseline and Month 6 glutathione in urine data.
Glutathione LLOQ = 0.01 uM, and ULOQ = 1.39 uM in urine.
Outcome measures
| Measure |
EPI-589
n=14 Participants
Participants received EPI-589 500 mg (2 tablets of 250 mg each) BID for 3 months, unless discontinued for safety or tolerability issues.
|
|---|---|
|
Level of Disease-Related Biomarker (Glutathione) in Urine
Baseline
|
0.12 µM
Interval 0.03 to 0.46
|
|
Level of Disease-Related Biomarker (Glutathione) in Urine
Month 6
|
0.17 µM
Interval 0.02 to 0.82
|
Adverse Events
EPI-589
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
EPI-589
n=19 participants at risk
Participants received EPI-589 500 mg (2 tablets of 250 mg each) BID for 3 months, unless discontinued for safety or tolerability issues.
|
|---|---|
|
Cardiac disorders
Aortic valve incompetence
|
5.3%
1/19 • Baseline (Day 0) to Month 6
Safety population included any participant who received at least 1 dose of EPI-589.
|
|
Ear and labyrinth disorders
Vertigo
|
5.3%
1/19 • Baseline (Day 0) to Month 6
Safety population included any participant who received at least 1 dose of EPI-589.
|
|
Eye disorders
Eye pain
|
5.3%
1/19 • Baseline (Day 0) to Month 6
Safety population included any participant who received at least 1 dose of EPI-589.
|
|
Eye disorders
Vision blurred
|
5.3%
1/19 • Baseline (Day 0) to Month 6
Safety population included any participant who received at least 1 dose of EPI-589.
|
|
Gastrointestinal disorders
Abdominal pain lower
|
5.3%
1/19 • Baseline (Day 0) to Month 6
Safety population included any participant who received at least 1 dose of EPI-589.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
5.3%
1/19 • Baseline (Day 0) to Month 6
Safety population included any participant who received at least 1 dose of EPI-589.
|
|
Gastrointestinal disorders
Constipation
|
5.3%
1/19 • Baseline (Day 0) to Month 6
Safety population included any participant who received at least 1 dose of EPI-589.
|
|
Gastrointestinal disorders
Diarrhoea
|
10.5%
2/19 • Baseline (Day 0) to Month 6
Safety population included any participant who received at least 1 dose of EPI-589.
|
|
Gastrointestinal disorders
Nausea
|
31.6%
6/19 • Baseline (Day 0) to Month 6
Safety population included any participant who received at least 1 dose of EPI-589.
|
|
Gastrointestinal disorders
Salivary hypersecretion
|
5.3%
1/19 • Baseline (Day 0) to Month 6
Safety population included any participant who received at least 1 dose of EPI-589.
|
|
Gastrointestinal disorders
Vomiting
|
5.3%
1/19 • Baseline (Day 0) to Month 6
Safety population included any participant who received at least 1 dose of EPI-589.
|
|
General disorders
Asthenia
|
5.3%
1/19 • Baseline (Day 0) to Month 6
Safety population included any participant who received at least 1 dose of EPI-589.
|
|
General disorders
Chest pain
|
5.3%
1/19 • Baseline (Day 0) to Month 6
Safety population included any participant who received at least 1 dose of EPI-589.
|
|
General disorders
Chills
|
10.5%
2/19 • Baseline (Day 0) to Month 6
Safety population included any participant who received at least 1 dose of EPI-589.
|
|
General disorders
Fatigue
|
5.3%
1/19 • Baseline (Day 0) to Month 6
Safety population included any participant who received at least 1 dose of EPI-589.
|
|
Immune system disorders
Hypersensitivity
|
5.3%
1/19 • Baseline (Day 0) to Month 6
Safety population included any participant who received at least 1 dose of EPI-589.
|
|
Immune system disorders
Seasonal allergy
|
5.3%
1/19 • Baseline (Day 0) to Month 6
Safety population included any participant who received at least 1 dose of EPI-589.
|
|
Infections and infestations
Clostridium difficile infection
|
5.3%
1/19 • Baseline (Day 0) to Month 6
Safety population included any participant who received at least 1 dose of EPI-589.
|
|
Infections and infestations
Nasopharyngitis
|
15.8%
3/19 • Baseline (Day 0) to Month 6
Safety population included any participant who received at least 1 dose of EPI-589.
|
|
Infections and infestations
Urinary tract infection
|
5.3%
1/19 • Baseline (Day 0) to Month 6
Safety population included any participant who received at least 1 dose of EPI-589.
|
|
Injury, poisoning and procedural complications
Contusion
|
10.5%
2/19 • Baseline (Day 0) to Month 6
Safety population included any participant who received at least 1 dose of EPI-589.
|
|
Injury, poisoning and procedural complications
Fall
|
26.3%
5/19 • Baseline (Day 0) to Month 6
Safety population included any participant who received at least 1 dose of EPI-589.
|
|
Injury, poisoning and procedural complications
Post lumbar puncture syndrome
|
5.3%
1/19 • Baseline (Day 0) to Month 6
Safety population included any participant who received at least 1 dose of EPI-589.
|
|
Injury, poisoning and procedural complications
Upper limb fracture
|
5.3%
1/19 • Baseline (Day 0) to Month 6
Safety population included any participant who received at least 1 dose of EPI-589.
|
|
Investigations
Alanine aminotransferase increased
|
5.3%
1/19 • Baseline (Day 0) to Month 6
Safety population included any participant who received at least 1 dose of EPI-589.
|
|
Investigations
Aspartate aminotransferase increased
|
5.3%
1/19 • Baseline (Day 0) to Month 6
Safety population included any participant who received at least 1 dose of EPI-589.
|
|
Investigations
Blood pressure increased
|
5.3%
1/19 • Baseline (Day 0) to Month 6
Safety population included any participant who received at least 1 dose of EPI-589.
|
|
Investigations
Blood testosterone decreased
|
5.3%
1/19 • Baseline (Day 0) to Month 6
Safety population included any participant who received at least 1 dose of EPI-589.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
15.8%
3/19 • Baseline (Day 0) to Month 6
Safety population included any participant who received at least 1 dose of EPI-589.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
21.1%
4/19 • Baseline (Day 0) to Month 6
Safety population included any participant who received at least 1 dose of EPI-589.
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
5.3%
1/19 • Baseline (Day 0) to Month 6
Safety population included any participant who received at least 1 dose of EPI-589.
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
5.3%
1/19 • Baseline (Day 0) to Month 6
Safety population included any participant who received at least 1 dose of EPI-589.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
5.3%
1/19 • Baseline (Day 0) to Month 6
Safety population included any participant who received at least 1 dose of EPI-589.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
5.3%
1/19 • Baseline (Day 0) to Month 6
Safety population included any participant who received at least 1 dose of EPI-589.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign hepatic neoplasm
|
5.3%
1/19 • Baseline (Day 0) to Month 6
Safety population included any participant who received at least 1 dose of EPI-589.
|
|
Nervous system disorders
Aura
|
5.3%
1/19 • Baseline (Day 0) to Month 6
Safety population included any participant who received at least 1 dose of EPI-589.
|
|
Nervous system disorders
Balance disorder
|
5.3%
1/19 • Baseline (Day 0) to Month 6
Safety population included any participant who received at least 1 dose of EPI-589.
|
|
Nervous system disorders
Dizziness
|
10.5%
2/19 • Baseline (Day 0) to Month 6
Safety population included any participant who received at least 1 dose of EPI-589.
|
|
Nervous system disorders
Dysarthria
|
5.3%
1/19 • Baseline (Day 0) to Month 6
Safety population included any participant who received at least 1 dose of EPI-589.
|
|
Nervous system disorders
Headache
|
15.8%
3/19 • Baseline (Day 0) to Month 6
Safety population included any participant who received at least 1 dose of EPI-589.
|
|
Nervous system disorders
Hypoaesthesia
|
5.3%
1/19 • Baseline (Day 0) to Month 6
Safety population included any participant who received at least 1 dose of EPI-589.
|
|
Nervous system disorders
Hypokinesia
|
5.3%
1/19 • Baseline (Day 0) to Month 6
Safety population included any participant who received at least 1 dose of EPI-589.
|
|
Nervous system disorders
Paraesthesia
|
5.3%
1/19 • Baseline (Day 0) to Month 6
Safety population included any participant who received at least 1 dose of EPI-589.
|
|
Nervous system disorders
Tension headache
|
5.3%
1/19 • Baseline (Day 0) to Month 6
Safety population included any participant who received at least 1 dose of EPI-589.
|
|
Psychiatric disorders
Depression
|
5.3%
1/19 • Baseline (Day 0) to Month 6
Safety population included any participant who received at least 1 dose of EPI-589.
|
|
Psychiatric disorders
Disorientation
|
5.3%
1/19 • Baseline (Day 0) to Month 6
Safety population included any participant who received at least 1 dose of EPI-589.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
5.3%
1/19 • Baseline (Day 0) to Month 6
Safety population included any participant who received at least 1 dose of EPI-589.
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
10.5%
2/19 • Baseline (Day 0) to Month 6
Safety population included any participant who received at least 1 dose of EPI-589.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
21.1%
4/19 • Baseline (Day 0) to Month 6
Safety population included any participant who received at least 1 dose of EPI-589.
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
5.3%
1/19 • Baseline (Day 0) to Month 6
Safety population included any participant who received at least 1 dose of EPI-589.
|
|
Skin and subcutaneous tissue disorders
Acne
|
5.3%
1/19 • Baseline (Day 0) to Month 6
Safety population included any participant who received at least 1 dose of EPI-589.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The Sponsor can review results and/or communications prior to public release and can embargo communications regarding trial results for a period that is up to 180 days from the time submitted to the sponsor for review. The sponsor may consult with the PI to require changes to the communication or extend the embargo.
- Publication restrictions are in place
Restriction type: OTHER