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EPI-743 for Metabolism or Mitochondrial Disorders

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01642056
Recruitment Status : Completed
First Posted : July 17, 2012
Results First Posted : April 14, 2021
Last Update Posted : April 14, 2021
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Human Genome Research Institute (NHGRI) )

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Crossover Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Conditions Mitochondrial Disease
Neurology
Myopathy
Interventions Drug: EPI-743
Drug: Placebo
Enrollment 20
Recruitment Details  
Pre-assignment Details 20 subjects were consented. One subject died during first intervention due to progression of disease. Three subjects did not complete the second intervention.
Arm/Group Title EPI-743, Then Placebo Placebo, Then EPI-743
Hide Arm/Group Description 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. 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.
Period Title: First Intervention
Started 10 10
Completed 9 10
Not Completed 1 0
Period Title: Second Intervention
Started 9 10
Completed 8 8
Not Completed 1 2
Arm/Group Title EPI-743, Then Placebo Placebo, Then EPI-743 Total
Hide Arm/Group Description 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. 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 of all reporting groups
Overall Number of Baseline Participants 10 10 20
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 10 participants 20 participants
<=18 years
10
 100.0%
10
 100.0%
20
 100.0%
Between 18 and 65 years
0
   0.0%
0
   0.0%
0
   0.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 10 participants 20 participants
Female
3
  30.0%
5
  50.0%
8
  40.0%
Male
7
  70.0%
5
  50.0%
12
  60.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 10 participants 20 participants
Hispanic or Latino
0
   0.0%
1
  10.0%
1
   5.0%
Not Hispanic or Latino
9
  90.0%
9
  90.0%
18
  90.0%
Unknown or Not Reported
1
  10.0%
0
   0.0%
1
   5.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 10 participants 20 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
3
  30.0%
1
  10.0%
4
  20.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
1
  10.0%
0
   0.0%
1
   5.0%
White
4
  40.0%
9
  90.0%
13
  65.0%
More than one race
1
  10.0%
0
   0.0%
1
   5.0%
Unknown or Not Reported
1
  10.0%
0
   0.0%
1
   5.0%
1.Primary Outcome
Title Newcastle Paediatric Mitochondrial Disease Scale (NPMDS) Part I-III, Baseline
Hide Description

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.

Time Frame Baseline - Day 0
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title EPI-743, Then Placebo Placebo, Then EPI-743
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 10 10
Mean (Standard Error)
Unit of Measure: Units on a scale
23.9  (2.8) 20.4  (3.7)
2.Primary Outcome
Title Newcastle Paediatric Mitochondrial Disease Scale (NPMDS) Part I-III, 6 Months
Hide Description

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.

Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
(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.
Arm/Group Title EPI-743, Then Placebo Placebo, Then EPI-743
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 9 10
Mean (Standard Error)
Unit of Measure: Units on a scale
27.1  (2.7) 20.2  (3.8)
3.Primary Outcome
Title Newcastle Paediatric Mitochondrial Disease Scale (NPMDS) Part I-III, Post Washout
Hide Description

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.

Time Frame 8 month - Post washout
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title EPI-743, Then Placebo Placebo, Then EPI-743
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 9 10
Mean (Standard Error)
Unit of Measure: Units on a scale
27.1  (3.5) 18.3  (3.6)
4.Primary Outcome
Title Newcastle Paediatric Mitochondrial Disease Scale (NPMDS) Part I-III, 14 Months
Hide Description

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.

Time Frame 14 months
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title EPI-743, Then Placebo Placebo, Then EPI-743
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 8 8
Mean (Standard Error)
Unit of Measure: Units on a scale
26  (3.3) 15.8  (3.7)
Time Frame 14 Months
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title EPI-743 Placebo
Hide Arm/Group Description 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. Received Placebo three times daily orally or via gastric tube with meals.
All-Cause Mortality
EPI-743 Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   1/20 (5.00%)      0/19 (0.00%)    
Hide Serious Adverse Events
EPI-743 Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/20 (15.00%)      4/19 (21.05%)    
General disorders     
Hyperthermia   0/20 (0.00%)  1/19 (5.26%)  1
Investigations     
Blood creatine phosphokinase increased   1/20 (5.00%)  3 0/19 (0.00%) 
Nervous system disorders     
Status epilepticus   1/20 (5.00%)  1 0/19 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Respiratory tract infection   0/20 (0.00%)  1/19 (5.26%)  1
Surgical and medical procedures     
Hospitalisation   2/20 (10.00%)  3 4/19 (21.05%)  6
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
EPI-743 Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   17/20 (85.00%)      18/19 (94.74%)    
Blood and lymphatic system disorders     
Anaemia   0/20 (0.00%)  2/19 (10.53%)  3
Polycythaemia   2/20 (10.00%)  3 5/19 (26.32%)  5
Ear and labyrinth disorders     
Tinnitus   0/20 (0.00%)  1/19 (5.26%)  1
Endocrine disorders     
Adrenal insufficiency   1/20 (5.00%)  1 0/19 (0.00%) 
Goitre   1/20 (5.00%)  1 0/19 (0.00%) 
Hypercalcaemia   0/20 (0.00%)  1/19 (5.26%)  1
Hyperthyroidism   1/20 (5.00%)  1 2/19 (10.53%)  2
Hypothyroidism   3/20 (15.00%)  4 1/19 (5.26%)  1
Gastrointestinal disorders     
Diarrhoea   0/20 (0.00%)  2/19 (10.53%)  2
Gastroenteritis viral   1/20 (5.00%)  1 0/19 (0.00%) 
Nausea   0/20 (0.00%)  1/19 (5.26%)  1
Pharyngitis   0/20 (0.00%)  1/19 (5.26%)  1
Vomiting   4/20 (20.00%)  4 4/19 (21.05%)  5
General disorders     
Fatigue   0/20 (0.00%)  2/19 (10.53%)  2
Hyperthermia   0/20 (0.00%)  6/19 (31.58%)  6
Influenza like illness   0/20 (0.00%)  1/19 (5.26%)  1
Hepatobiliary disorders     
Hyperammonaemia   1/20 (5.00%)  1 0/19 (0.00%) 
Investigations     
Activated partial thromboplastin time prolonged   3/20 (15.00%)  4 5/19 (26.32%)  6
Alanine aminotransferase increased   4/20 (20.00%)  7 4/19 (21.05%)  5
Amylase increased   1/20 (5.00%)  1 3/19 (15.79%)  3
Aspartate aminotransferase increased   4/20 (20.00%)  5 4/19 (21.05%)  6
Blood albumin decreased   0/20 (0.00%)  2/19 (10.53%)  3
Blood alkaline phosphatase increased   2/20 (10.00%)  3 1/19 (5.26%)  1
Blood creatine phosphokinase increased   10/20 (50.00%)  14 6/19 (31.58%)  10
Electrocardiogram QT prolonged   1/20 (5.00%)  1 1/19 (5.26%)  2
International normalised ratio increased   1/20 (5.00%)  1 0/19 (0.00%) 
Lipase increased   1/20 (5.00%)  1 0/19 (0.00%) 
Lymphocyte count increased   0/20 (0.00%)  1/19 (5.26%)  1
Neutrophil count decreased   1/20 (5.00%)  1 2/19 (10.53%)  2
Platelet count decreased   1/20 (5.00%)  1 2/19 (10.53%)  2
Prothrombin time prolonged   1/20 (5.00%)  1 0/19 (0.00%) 
Red blood cell sedimentation rate increased   1/20 (5.00%)  1 0/19 (0.00%) 
White blood cell count decreased   1/20 (5.00%)  1 2/19 (10.53%)  2
Metabolism and nutrition disorders     
Dehydration   0/20 (0.00%)  1/19 (5.26%)  1
Hyperbilirubinaemia   1/20 (5.00%)  1 0/19 (0.00%) 
Hypercholesterolaemia   1/20 (5.00%)  1 0/19 (0.00%) 
Hyperkalaemia   1/20 (5.00%)  2 1/19 (5.26%)  1
Hypernatraemia   2/20 (10.00%)  2 0/19 (0.00%) 
Hypocalcaemia   0/20 (0.00%)  1/19 (5.26%)  1
Hypoglycaemia   2/20 (10.00%)  2 1/19 (5.26%)  1
Hyponatraemia   0/20 (0.00%)  1/19 (5.26%)  1
Psychiatric disorders     
Psychomotor hyperactivity   0/20 (0.00%)  1/19 (5.26%)  1
Violence-related symptom   0/20 (0.00%)  1/19 (5.26%)  1
Renal and urinary disorders     
Proteinuria   1/20 (5.00%)  1 0/19 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Cough   2/20 (10.00%)  2 2/19 (10.53%)  2
Nasal congestion   1/20 (5.00%)  1 0/19 (0.00%) 
Upper respiratory tract irritation   2/20 (10.00%)  2 1/19 (5.26%)  1
Wheezing   1/20 (5.00%)  1 0/19 (0.00%) 
Skin and subcutaneous tissue disorders     
Rash   1/20 (5.00%)  1 0/19 (0.00%) 
Indicates events were collected by systematic assessment
All 20 randomized patients were included in the model to assess baseline characteristics. Of the 20 randomized, 19 provided 6-month outcomes (10 placebo, 9 treatment), who then crossed over their treatments and provided 8-month baseline scores. Of these, 16 provided 14-month outcomes (8 who had crossed over to treatment, and 8 who had crossed over to placebo).
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Gahl, William
Organization: National Human Genome Research Institute
Phone: +1 301 402 2739
EMail: gahlw@mail.nih.gov
Layout table for additonal information
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Human Genome Research Institute (NHGRI) )
ClinicalTrials.gov Identifier: NCT01642056    
Other Study ID Numbers: 120161
12-HG-0161
First Submitted: July 14, 2012
First Posted: July 17, 2012
Results First Submitted: February 19, 2021
Results First Posted: April 14, 2021
Last Update Posted: April 14, 2021