Trial Outcomes & Findings for EPI-743 for Metabolism or Mitochondrial Disorders (NCT NCT01642056)
NCT ID: NCT01642056
Last Updated: 2021-04-14
Results Overview
NPMDS is a semi-quantitative clinical rating scale that evaluates the progression of mitochondrial disease in pediatric patients. The NPMDS scale provides an assessment of the progression of mitochondrial disease. Scores from Parts I-III are added to get a value between 0 and 130, with higher scores representing more severe disease.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
20 participants
Primary outcome timeframe
Baseline - Day 0
Results posted on
2021-04-14
Participant Flow
20 subjects were consented. One subject died during first intervention due to progression of disease. Three subjects did not complete the second intervention.
Participant milestones
| Measure |
EPI-743, Then Placebo
Received EPI-743, 15mg/kg up to a maximum dose of 200 mg orally or via gastric tube three times daily with meals, then placebo three times daily orally or via gastric tube with meals. EPI-743 is structurally related to Vitamin E and can be broadly classified as an antioxidant.
|
Placebo, Then EPI-743
Received Placebo three times daily orally or via gastric tube with meals, then EPI-743, 15mg/kg up to a maximum dose of 200 mg three times daily orally or via gastric tube with meals. EPI-743 is structurally related to Vitamin E and can be broadly classified as an antioxidant.
|
|---|---|---|
|
First Intervention
STARTED
|
10
|
10
|
|
First Intervention
COMPLETED
|
9
|
10
|
|
First Intervention
NOT COMPLETED
|
1
|
0
|
|
Second Intervention
STARTED
|
9
|
10
|
|
Second Intervention
COMPLETED
|
8
|
8
|
|
Second Intervention
NOT COMPLETED
|
1
|
2
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
EPI-743 for Metabolism or Mitochondrial Disorders
Baseline characteristics by cohort
| Measure |
EPI-743, Then Placebo
n=10 Participants
Received EPI-743, 15mg/kg up to a maximum dose of 200 mg orally or via gastric tube three times daily with meals, then placebo three times daily orally or via gastric tube with meals. EPI-743 is structurally related to Vitamin E and can be broadly classified as an antioxidant.
|
Placebo, Then EPI-743
n=10 Participants
Received Placebo three times daily orally or via gastric tube with meals, then EPI-743, 15mg/kg up to a maximum dose of 200 mg three times daily orally or via gastric tube with meals. EPI-743 is structurally related to Vitamin E and can be broadly classified as an antioxidant.
|
Total
n=20 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Age, Categorical
<=18 years
|
10 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
9 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
4 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline - Day 0Population: Participants who who had treatment intervention in phase I. The outcome measures were analyzed separately by arm and phase, not by combining results by intervention across phases, due to the progressive nature of the underlying disease.
NPMDS is a semi-quantitative clinical rating scale that evaluates the progression of mitochondrial disease in pediatric patients. The NPMDS scale provides an assessment of the progression of mitochondrial disease. Scores from Parts I-III are added to get a value between 0 and 130, with higher scores representing more severe disease.
Outcome measures
| Measure |
EPI-743, Then Placebo
n=10 Participants
Received EPI-743, 15mg/kg up to a maximum dose of 200 mg orally or via gastric tube three times daily with meals, then placebo three times daily orally or via gastric tube with meals. EPI-743 is structurally related to Vitamin E and can be broadly classified as an antioxidant.
|
Placebo, Then EPI-743
n=10 Participants
Received Placebo three times daily orally or via gastric tube with meals, then EPI-743, 15mg/kg up to a maximum dose of 200 mg three times daily orally or via gastric tube with meals. EPI-743 is structurally related to Vitamin E and can be broadly classified as an antioxidant.
|
|---|---|---|
|
Newcastle Paediatric Mitochondrial Disease Scale (NPMDS) Part I-III, Baseline
|
23.9 Units on a scale
Standard Error 2.8
|
20.4 Units on a scale
Standard Error 3.7
|
PRIMARY outcome
Timeframe: 6 monthsPopulation: (Participants who who had treatment intervention in phase I. The outcome measures were analyzed separately by arm and phase, not by combining results by intervention across phases, due to the progressive nature of the underlying disease.
NPMDS is a semi-quantitative clinical rating scale that evaluates the progression of mitochondrial disease in pediatric patients. The NPMDS scale provides an assessment of the progression of mitochondrial disease. Scores from Parts I-III are added to get a value between 0 and 130, with higher scores representing more severe disease.
Outcome measures
| Measure |
EPI-743, Then Placebo
n=9 Participants
Received EPI-743, 15mg/kg up to a maximum dose of 200 mg orally or via gastric tube three times daily with meals, then placebo three times daily orally or via gastric tube with meals. EPI-743 is structurally related to Vitamin E and can be broadly classified as an antioxidant.
|
Placebo, Then EPI-743
n=10 Participants
Received Placebo three times daily orally or via gastric tube with meals, then EPI-743, 15mg/kg up to a maximum dose of 200 mg three times daily orally or via gastric tube with meals. EPI-743 is structurally related to Vitamin E and can be broadly classified as an antioxidant.
|
|---|---|---|
|
Newcastle Paediatric Mitochondrial Disease Scale (NPMDS) Part I-III, 6 Months
|
27.1 Units on a scale
Standard Error 2.7
|
20.2 Units on a scale
Standard Error 3.8
|
PRIMARY outcome
Timeframe: 8 month - Post washoutPopulation: Participants who received treatment in phase II. The outcome measures were analyzed separately by arm and phase, not by combining results by intervention across phases, due to the progressive nature of the underlying disease.
NPMDS is a semi-quantitative clinical rating scale that evaluates the progression of mitochondrial disease in pediatric patients. The NPMDS scale provides an assessment of the progression of mitochondrial disease. Scores from Parts I-III are added to get a value between 0 and 130, with higher scores representing more severe disease.
Outcome measures
| Measure |
EPI-743, Then Placebo
n=9 Participants
Received EPI-743, 15mg/kg up to a maximum dose of 200 mg orally or via gastric tube three times daily with meals, then placebo three times daily orally or via gastric tube with meals. EPI-743 is structurally related to Vitamin E and can be broadly classified as an antioxidant.
|
Placebo, Then EPI-743
n=10 Participants
Received Placebo three times daily orally or via gastric tube with meals, then EPI-743, 15mg/kg up to a maximum dose of 200 mg three times daily orally or via gastric tube with meals. EPI-743 is structurally related to Vitamin E and can be broadly classified as an antioxidant.
|
|---|---|---|
|
Newcastle Paediatric Mitochondrial Disease Scale (NPMDS) Part I-III, Post Washout
|
27.1 Units on a scale
Standard Error 3.5
|
18.3 Units on a scale
Standard Error 3.6
|
PRIMARY outcome
Timeframe: 14 monthsPopulation: Participants who received treatment in phase II. The outcome measures were analyzed separately by arm and phase, not by combining results by intervention across phases, due to the progressive nature of the underlying disease.
NPMDS is a semi-quantitative clinical rating scale that evaluates the progression of mitochondrial disease in pediatric patients. The NPMDS scale provides an assessment of the progression of mitochondrial disease. Scores from Parts I-III are added to get a value between 0 and 130, with higher scores representing more severe disease.
Outcome measures
| Measure |
EPI-743, Then Placebo
n=8 Participants
Received EPI-743, 15mg/kg up to a maximum dose of 200 mg orally or via gastric tube three times daily with meals, then placebo three times daily orally or via gastric tube with meals. EPI-743 is structurally related to Vitamin E and can be broadly classified as an antioxidant.
|
Placebo, Then EPI-743
n=8 Participants
Received Placebo three times daily orally or via gastric tube with meals, then EPI-743, 15mg/kg up to a maximum dose of 200 mg three times daily orally or via gastric tube with meals. EPI-743 is structurally related to Vitamin E and can be broadly classified as an antioxidant.
|
|---|---|---|
|
Newcastle Paediatric Mitochondrial Disease Scale (NPMDS) Part I-III, 14 Months
|
26 Units on a scale
Standard Error 3.3
|
15.8 Units on a scale
Standard Error 3.7
|
Adverse Events
EPI-743
Serious events: 3 serious events
Other events: 17 other events
Deaths: 1 deaths
Placebo
Serious events: 4 serious events
Other events: 18 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
EPI-743
n=20 participants at risk
Received EPI-743, 15mg/kg up to a maximum dose of 200 mg orally or via gastric tube three times daily with meals. EPI-743 is structurally related to Vitamin E and can be broadly classified as an antioxidant.
|
Placebo
n=19 participants at risk
Received Placebo three times daily orally or via gastric tube with meals.
|
|---|---|---|
|
General disorders
Hyperthermia
|
0.00%
0/20 • 14 Months
|
5.3%
1/19 • Number of events 1 • 14 Months
|
|
Investigations
Blood creatine phosphokinase increased
|
5.0%
1/20 • Number of events 3 • 14 Months
|
0.00%
0/19 • 14 Months
|
|
Nervous system disorders
Status epilepticus
|
5.0%
1/20 • Number of events 1 • 14 Months
|
0.00%
0/19 • 14 Months
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory tract infection
|
0.00%
0/20 • 14 Months
|
5.3%
1/19 • Number of events 1 • 14 Months
|
|
Surgical and medical procedures
Hospitalisation
|
10.0%
2/20 • Number of events 3 • 14 Months
|
21.1%
4/19 • Number of events 6 • 14 Months
|
Other adverse events
| Measure |
EPI-743
n=20 participants at risk
Received EPI-743, 15mg/kg up to a maximum dose of 200 mg orally or via gastric tube three times daily with meals. EPI-743 is structurally related to Vitamin E and can be broadly classified as an antioxidant.
|
Placebo
n=19 participants at risk
Received Placebo three times daily orally or via gastric tube with meals.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/20 • 14 Months
|
10.5%
2/19 • Number of events 3 • 14 Months
|
|
Blood and lymphatic system disorders
Polycythaemia
|
10.0%
2/20 • Number of events 3 • 14 Months
|
26.3%
5/19 • Number of events 5 • 14 Months
|
|
Ear and labyrinth disorders
Tinnitus
|
0.00%
0/20 • 14 Months
|
5.3%
1/19 • Number of events 1 • 14 Months
|
|
Endocrine disorders
Adrenal insufficiency
|
5.0%
1/20 • Number of events 1 • 14 Months
|
0.00%
0/19 • 14 Months
|
|
Endocrine disorders
Goitre
|
5.0%
1/20 • Number of events 1 • 14 Months
|
0.00%
0/19 • 14 Months
|
|
Endocrine disorders
Hypercalcaemia
|
0.00%
0/20 • 14 Months
|
5.3%
1/19 • Number of events 1 • 14 Months
|
|
Endocrine disorders
Hyperthyroidism
|
5.0%
1/20 • Number of events 1 • 14 Months
|
10.5%
2/19 • Number of events 2 • 14 Months
|
|
Endocrine disorders
Hypothyroidism
|
15.0%
3/20 • Number of events 4 • 14 Months
|
5.3%
1/19 • Number of events 1 • 14 Months
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/20 • 14 Months
|
10.5%
2/19 • Number of events 2 • 14 Months
|
|
Gastrointestinal disorders
Gastroenteritis viral
|
5.0%
1/20 • Number of events 1 • 14 Months
|
0.00%
0/19 • 14 Months
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/20 • 14 Months
|
5.3%
1/19 • Number of events 1 • 14 Months
|
|
Gastrointestinal disorders
Pharyngitis
|
0.00%
0/20 • 14 Months
|
5.3%
1/19 • Number of events 1 • 14 Months
|
|
Gastrointestinal disorders
Vomiting
|
20.0%
4/20 • Number of events 4 • 14 Months
|
21.1%
4/19 • Number of events 5 • 14 Months
|
|
General disorders
Fatigue
|
0.00%
0/20 • 14 Months
|
10.5%
2/19 • Number of events 2 • 14 Months
|
|
General disorders
Hyperthermia
|
0.00%
0/20 • 14 Months
|
31.6%
6/19 • Number of events 6 • 14 Months
|
|
General disorders
Influenza like illness
|
0.00%
0/20 • 14 Months
|
5.3%
1/19 • Number of events 1 • 14 Months
|
|
Hepatobiliary disorders
Hyperammonaemia
|
5.0%
1/20 • Number of events 1 • 14 Months
|
0.00%
0/19 • 14 Months
|
|
Investigations
Activated partial thromboplastin time prolonged
|
15.0%
3/20 • Number of events 4 • 14 Months
|
26.3%
5/19 • Number of events 6 • 14 Months
|
|
Investigations
Alanine aminotransferase increased
|
20.0%
4/20 • Number of events 7 • 14 Months
|
21.1%
4/19 • Number of events 5 • 14 Months
|
|
Investigations
Amylase increased
|
5.0%
1/20 • Number of events 1 • 14 Months
|
15.8%
3/19 • Number of events 3 • 14 Months
|
|
Investigations
Aspartate aminotransferase increased
|
20.0%
4/20 • Number of events 5 • 14 Months
|
21.1%
4/19 • Number of events 6 • 14 Months
|
|
Investigations
Blood albumin decreased
|
0.00%
0/20 • 14 Months
|
10.5%
2/19 • Number of events 3 • 14 Months
|
|
Investigations
Blood alkaline phosphatase increased
|
10.0%
2/20 • Number of events 3 • 14 Months
|
5.3%
1/19 • Number of events 1 • 14 Months
|
|
Investigations
Blood creatine phosphokinase increased
|
50.0%
10/20 • Number of events 14 • 14 Months
|
31.6%
6/19 • Number of events 10 • 14 Months
|
|
Investigations
Electrocardiogram QT prolonged
|
5.0%
1/20 • Number of events 1 • 14 Months
|
5.3%
1/19 • Number of events 2 • 14 Months
|
|
Investigations
International normalised ratio increased
|
5.0%
1/20 • Number of events 1 • 14 Months
|
0.00%
0/19 • 14 Months
|
|
Investigations
Lipase increased
|
5.0%
1/20 • Number of events 1 • 14 Months
|
0.00%
0/19 • 14 Months
|
|
Investigations
Lymphocyte count increased
|
0.00%
0/20 • 14 Months
|
5.3%
1/19 • Number of events 1 • 14 Months
|
|
Investigations
Neutrophil count decreased
|
5.0%
1/20 • Number of events 1 • 14 Months
|
10.5%
2/19 • Number of events 2 • 14 Months
|
|
Investigations
Platelet count decreased
|
5.0%
1/20 • Number of events 1 • 14 Months
|
10.5%
2/19 • Number of events 2 • 14 Months
|
|
Investigations
Prothrombin time prolonged
|
5.0%
1/20 • Number of events 1 • 14 Months
|
0.00%
0/19 • 14 Months
|
|
Investigations
Red blood cell sedimentation rate increased
|
5.0%
1/20 • Number of events 1 • 14 Months
|
0.00%
0/19 • 14 Months
|
|
Investigations
White blood cell count decreased
|
5.0%
1/20 • Number of events 1 • 14 Months
|
10.5%
2/19 • Number of events 2 • 14 Months
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/20 • 14 Months
|
5.3%
1/19 • Number of events 1 • 14 Months
|
|
Metabolism and nutrition disorders
Hyperbilirubinaemia
|
5.0%
1/20 • Number of events 1 • 14 Months
|
0.00%
0/19 • 14 Months
|
|
Metabolism and nutrition disorders
Hypercholesterolaemia
|
5.0%
1/20 • Number of events 1 • 14 Months
|
0.00%
0/19 • 14 Months
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
5.0%
1/20 • Number of events 2 • 14 Months
|
5.3%
1/19 • Number of events 1 • 14 Months
|
|
Metabolism and nutrition disorders
Hypernatraemia
|
10.0%
2/20 • Number of events 2 • 14 Months
|
0.00%
0/19 • 14 Months
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
0.00%
0/20 • 14 Months
|
5.3%
1/19 • Number of events 1 • 14 Months
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
10.0%
2/20 • Number of events 2 • 14 Months
|
5.3%
1/19 • Number of events 1 • 14 Months
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/20 • 14 Months
|
5.3%
1/19 • Number of events 1 • 14 Months
|
|
Psychiatric disorders
Psychomotor hyperactivity
|
0.00%
0/20 • 14 Months
|
5.3%
1/19 • Number of events 1 • 14 Months
|
|
Psychiatric disorders
Violence-related symptom
|
0.00%
0/20 • 14 Months
|
5.3%
1/19 • Number of events 1 • 14 Months
|
|
Renal and urinary disorders
Proteinuria
|
5.0%
1/20 • Number of events 1 • 14 Months
|
0.00%
0/19 • 14 Months
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
10.0%
2/20 • Number of events 2 • 14 Months
|
10.5%
2/19 • Number of events 2 • 14 Months
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
5.0%
1/20 • Number of events 1 • 14 Months
|
0.00%
0/19 • 14 Months
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract irritation
|
10.0%
2/20 • Number of events 2 • 14 Months
|
5.3%
1/19 • Number of events 1 • 14 Months
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
5.0%
1/20 • Number of events 1 • 14 Months
|
0.00%
0/19 • 14 Months
|
|
Skin and subcutaneous tissue disorders
Rash
|
5.0%
1/20 • Number of events 1 • 14 Months
|
0.00%
0/19 • 14 Months
|
Additional Information
Gahl, William
National Human Genome Research Institute
Phone: +1 301 402 2739
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place