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Efficacy of Prednisone In the Treatment of Ocular Myasthenia (EPITOME')

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ClinicalTrials.gov Identifier: NCT00995722
Recruitment Status : Terminated (Slow recruitment rate)
First Posted : October 15, 2009
Results First Posted : November 2, 2015
Last Update Posted : June 2, 2017
Sponsor:
Collaborators:
University of Miami
University of Rochester
Information provided by (Responsible Party):
Michael Benatar, University of Miami

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Ocular Myasthenia Gravis
Interventions Drug: Prednisone
Drug: Placebo
Enrollment 11
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Prednisone Placebo
Hide Arm/Group Description

Corticosteroid

Prednisone: Prednisone will be adjusted based on combined measures of tolerability and efficacy. Capsules will contain 10mg of prednisone.

Pyridostigmine: Prior to randomization, pyridostigmine dosage increments will be made as needed for myasthenic symptoms and as tolerated according to a pre-specified dosage titration schedule. Following randomization, dose will remain constant.

Matched, inactive substance

Placebo: Placebo dosages will be adjusted based on combined measures of tolerability and efficacy. Capsules will contain matching placebo.

Pyridostigmine: Prior to randomization, pyridostigmine dosage increments will be made as needed for myasthenic symptoms and as tolerated according to a pre-specified dosage titration schedule. Following randomization, dose will remain constant.

Period Title: Double Blinded: 16 Weeks
Started 6 5
Completed 5 4
Not Completed 1 1
Period Title: Overall Study: 36 Weeks
Started 5 4
Completed 3 2
Not Completed 2 2
Arm/Group Title Prednisone Placebo Total
Hide Arm/Group Description

Corticosteroid

Prednisone: Prednisone will be adjusted based on combined measures of tolerability and efficacy. Capsules will contain 10mg of prednisone.

Pyridostigmine: Prior to randomization, pyridostigmine dosage increments will be made as needed for myasthenic symptoms and as tolerated according to a pre-specified dosage titration schedule. Following randomization, dose will remain constant.

Matched, inactive substance

Placebo: Placebo dosages will be adjusted based on combined measures of tolerability and efficacy. Capsules will contain matching placebo.

Pyridostigmine: Prior to randomization, pyridostigmine dosage increments will be made as needed for myasthenic symptoms and as tolerated according to a pre-specified dosage titration schedule. Following randomization, dose will remain constant.

Total of all reporting groups
Overall Number of Baseline Participants 6 5 11
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 5 participants 11 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
6
 100.0%
5
 100.0%
11
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 6 participants 5 participants 11 participants
64  (18) 62  (9) 63  (13.6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 5 participants 11 participants
Female
2
  33.3%
3
  60.0%
5
  45.5%
Male
4
  66.7%
2
  40.0%
6
  54.5%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 5 participants 11 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
0
   0.0%
Not Hispanic or Latino
6
 100.0%
5
 100.0%
11
 100.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 5 participants 11 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
2
  33.3%
1
  20.0%
3
  27.3%
White
4
  66.7%
4
  80.0%
8
  72.7%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Treatment Failure
Hide Description Failure to achive sustatined minimal manifestation status by week 16
Time Frame 4 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Prednisone Placebo
Hide Arm/Group Description:

Corticosteroid

Prednisone: Prednisone will be adjusted based on combined measures of tolerability and efficacy. Capsules will contain 10mg of prednisone.

Pyridostigmine: Prior to randomization, pyridostigmine dosage increments will be made as needed for myasthenic symptoms and as tolerated according to a pre-specified dosage titration schedule. Following randomization, dose will remain constant.

Matched, inactive substance

Placebo: Placebo dosages will be adjusted based on combined measures of tolerability and efficacy. Capsules will contain matching placebo.

Pyridostigmine: Prior to randomization, pyridostigmine dosage increments will be made as needed for myasthenic symptoms and as tolerated according to a pre-specified dosage titration schedule. Following randomization, dose will remain constant.

Overall Number of Participants Analyzed 6 5
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
17
(0 to 64)
100
(48 to 100)
2.Secondary Outcome
Title Change in Ocular Quantitative Myasthenia Score From Baseline to Week 16
Hide Description [Not Specified]
Time Frame 4 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Prednisone Placebo
Hide Arm/Group Description:

Corticosteroid

Prednisone: Prednisone will be adjusted based on combined measures of tolerability and efficacy. Capsules will contain 10mg of prednisone.

Pyridostigmine: Prior to randomization, pyridostigmine dosage increments will be made as needed for myasthenic symptoms and as tolerated according to a pre-specified dosage titration schedule. Following randomization, dose will remain constant.

Matched, inactive substance

Placebo: Placebo dosages will be adjusted based on combined measures of tolerability and efficacy. Capsules will contain matching placebo.

Pyridostigmine: Prior to randomization, pyridostigmine dosage increments will be made as needed for myasthenic symptoms and as tolerated according to a pre-specified dosage titration schedule. Following randomization, dose will remain constant.

Overall Number of Participants Analyzed 6 5
Mean (95% Confidence Interval)
Unit of Measure: units on a scale
-2.25
(-5.56 to 1.05)
-0.05
(-3.71 to 3.60)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Prednisone, Placebo
Comments Mean Ocular QMG Changes from Baseline to Week 16 . 95% CI and p-values obtained from the analysis of covariance model to adjust for the baseline value of the outcome variable.
Type of Statistical Test Non-Inferiority or Equivalence
Comments N=80, (40 per group), 80% power to detect a group difference of 30%–35% and 5% significance level.
Statistical Test of Hypothesis P-Value 0.37
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA used to compare mean values adjusting for the baseline value
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.20
Confidence Interval (2-Sided) 95%
-7.20 to 2.8
Estimation Comments QMG Score ranges from 0-15, where 0 is normal and a reduction in score represents imrovement.
3.Secondary Outcome
Title Change in Quality of Life as Measured by the NEI-VFQ-25 Measures
Hide Description [Not Specified]
Time Frame 4 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Prednisone Placebo
Hide Arm/Group Description:

Corticosteroid

Prednisone: Prednisone will be adjusted based on combined measures of tolerability and efficacy. Capsules will contain 10mg of prednisone.

Pyridostigmine: Prior to randomization, pyridostigmine dosage increments will be made as needed for myasthenic symptoms and as tolerated according to a pre-specified dosage titration schedule. Following randomization, dose will remain constant.

Matched, inactive substance

Placebo: Placebo dosages will be adjusted based on combined measures of tolerability and efficacy. Capsules will contain matching placebo.

Pyridostigmine: Prior to randomization, pyridostigmine dosage increments will be made as needed for myasthenic symptoms and as tolerated according to a pre-specified dosage titration schedule. Following randomization, dose will remain constant.

Overall Number of Participants Analyzed 6 5
Mean (95% Confidence Interval)
Unit of Measure: units on a scale
10.7
(4.75 to 16.64)
4.14
(-2.54 to 10.82)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Prednisone, Placebo
Comments Mean Change in quality of life as measured by the NEI-VFQ-25 at the end of Double- Blinded Treatment. 95% CI and p-values obtained from the analysis of covariance model to adjust for the baseline value of the outcome variable.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Mean Change in quality of life as measured by the NEI-VFQ-25 at the end of Double- Blinded Treatment
Statistical Test of Hypothesis P-Value 0.13
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 6.56
Confidence Interval (2-Sided) 95%
-2.59 to 15.71
Estimation Comments Scores ranges fro 0-100 , where 100 is normal and an increase in score represents an improvement
4.Secondary Outcome
Title Change in Quality of Life as Measured by the MG-QOL-15 Score
Hide Description [Not Specified]
Time Frame 4 Months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Prednisone Placebo
Hide Arm/Group Description:

Corticosteroid

Prednisone: Prednisone will be adjusted based on combined measures of tolerability and efficacy. Capsules will contain 10mg of prednisone.

Pyridostigmine: Prior to randomization, pyridostigmine dosage increments will be made as needed for myasthenic symptoms and as tolerated according to a pre-specified dosage titration schedule. Following randomization, dose will remain constant.

Matched, inactive substance

Placebo: Placebo dosages will be adjusted based on combined measures of tolerability and efficacy. Capsules will contain matching placebo.

Pyridostigmine: Prior to randomization, pyridostigmine dosage increments will be made as needed for myasthenic symptoms and as tolerated according to a pre-specified dosage titration schedule. Following randomization, dose will remain constant.

Overall Number of Participants Analyzed 6 5
Mean (95% Confidence Interval)
Unit of Measure: units on a scale
-6.3
(-10.11 to -2.50)
-2.5
(-6.30 to 1.31)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Prednisone, Placebo
Comments Mean Change in quality if life as measured by the MG-QOL-15 score at the end of Double- Blinded Treatment. 95% CI and p-values obtained from the analysis of covariance model to adjust for the baseline value of the outcome variable.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Mean Change in quality if life as measured by the MG-QOL-15 score at the end of Double- Blinded Treatment
Statistical Test of Hypothesis P-Value 0.15
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.81
Confidence Interval (2-Sided) 95%
-9.37 to 1.75
Estimation Comments Ranges from 0-60, where 0 is Normal and a reduction in score represents improvement.
5.Secondary Outcome
Title Change in Quality of Life as Measured by the 10-Item Neuro-ophthalmological Supplement to the NEI-VFQ-25
Hide Description [Not Specified]
Time Frame 4 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Prednisone Placebo
Hide Arm/Group Description:

Corticosteroid

Prednisone: Prednisone will be adjusted based on combined measures of tolerability and efficacy. Capsules will contain 10mg of prednisone.

Pyridostigmine: Prior to randomization, pyridostigmine dosage increments will be made as needed for myasthenic symptoms and as tolerated according to a pre-specified dosage titration schedule. Following randomization, dose will remain constant.

Matched, inactive substance

Placebo: Placebo dosages will be adjusted based on combined measures of tolerability and efficacy. Capsules will contain matching placebo.

Pyridostigmine: Prior to randomization, pyridostigmine dosage increments will be made as needed for myasthenic symptoms and as tolerated according to a pre-specified dosage titration schedule. Following randomization, dose will remain constant.

Overall Number of Participants Analyzed 6 5
Mean (95% Confidence Interval)
Unit of Measure: units on a scale
15.28
(-0.62 to 31.17)
-1.7
(-19.83 to 16.43)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Prednisone, Placebo
Comments Mean Change NEI-VFQ-25 10 item neuro-opthtalmological supplement score baseline to week 16. 95% CI and p-values obtained from the analysis of covariance model to adjust for the baseline value of the outcome variable.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Mean Change NEI-VFQ-25 10 item neuro-opthtalmological supplement score baseline to week 16.
Statistical Test of Hypothesis P-Value 0.16
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 16.98
Confidence Interval (2-Sided) 95%
-9.22 to 43.17
Estimation Comments Ranges 0-100, where 100 is normal and an increase in score represents an improvement.
Time Frame Adverse Events After Randomization
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Prednisone Placebo
Hide Arm/Group Description

Corticosteroid

Prednisone: Prednisone will be adjusted based on combined measures of tolerability and efficacy. Capsules will contain 10mg of prednisone.

Pyridostigmine: Prior to randomization, pyridostigmine dosage increments will be made as needed for myasthenic symptoms and as tolerated according to a pre-specified dosage titration schedule. Following randomization, dose will remain constant.

Matched, inactive substance

Placebo: Placebo dosages will be adjusted based on combined measures of tolerability and efficacy. Capsules will contain matching placebo.

Pyridostigmine: Prior to randomization, pyridostigmine dosage increments will be made as needed for myasthenic symptoms and as tolerated according to a pre-specified dosage titration schedule. Following randomization, dose will remain constant.

All-Cause Mortality
Prednisone Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Prednisone Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/6 (16.67%)      2/5 (40.00%)    
Cardiac disorders     
SINUS TACHYCARDIA  1  0/6 (0.00%)  0 1/5 (20.00%)  1
PALPITATIONS  1  0/6 (0.00%)  0 1/5 (20.00%)  1
Gastrointestinal disorders     
GI BLEED  1  1/6 (16.67%)  1 0/5 (0.00%)  0
Infections and infestations     
DIVERTICULAR ABCESS  1  0/6 (0.00%)  0 1/5 (20.00%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE 3.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Prednisone Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/6 (100.00%)      4/5 (80.00%)    
Cardiac disorders     
ARRHYTMIA  1  1/6 (16.67%)  1 0/5 (0.00%)  0
CONDUCTION DISORDER  1  0/6 (0.00%)  0 1/5 (20.00%)  1
PALPITATIONS  2  0/6 (0.00%)  0 1/5 (20.00%)  1
SINUS TACHYCARDIA  2  0/6 (0.00%)  0 1/5 (20.00%)  1
Endocrine disorders     
IMPAIRED GLUCOSE TOLERANCE  1  1/6 (16.67%)  1 0/5 (0.00%)  0
WEIGHT GAIN  1  2/6 (33.33%)  2 0/5 (0.00%)  0
Eye disorders     
EYE PAIN(POCKET IN EYE)  1  0/6 (0.00%)  0 1/5 (20.00%)  1
Gastrointestinal disorders     
NAUSEA  1  2/6 (33.33%)  2 0/5 (0.00%)  0
DIARRHEA  1  2/6 (33.33%)  2 1/5 (20.00%)  1
CONSTIPATION  1  1/6 (16.67%)  1 0/5 (0.00%)  0
DYSPHAGIA  1  1/6 (16.67%)  1 0/5 (0.00%)  0
FLATULENCE  1  1/6 (16.67%)  1 0/5 (0.00%)  0
Musculoskeletal and connective tissue disorders     
EDEMA: HEAD AND NECK  1  1/6 (16.67%)  2 0/5 (0.00%)  0
MYALGIA  1  1/6 (16.67%)  1 0/5 (0.00%)  0
Nervous system disorders     
HEADACHE  1  1/6 (16.67%)  1 0/5 (0.00%)  0
INSOMNIA  1  0/6 (0.00%)  0 1/5 (20.00%)  1
AGITATION  1  1/6 (16.67%)  1 0/5 (0.00%)  0
ANXIETY  1  0/6 (0.00%)  0 1/5 (20.00%)  1
BLEPHAROSPASM  1  1/6 (16.67%)  1 0/5 (0.00%)  0
DIZZINESS  1  0/6 (0.00%)  0 1/5 (20.00%)  1
FACE FASCICULATION (RIGHT SIDE)  1  1/6 (16.67%)  1 0/5 (0.00%)  0
EYE FASCICULLATION  1  1/6 (16.67%)  1 0/5 (0.00%)  0
BLURRED VISION  2  1/6 (16.67%)  1 0/5 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
BRONCHITIS  1  1/6 (16.67%)  1 0/5 (0.00%)  0
Vascular disorders     
HEMATOMA  1  1/6 (16.67%)  1 0/5 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, OTHER
2
Term from vocabulary, CTCAE 3.0
Early termination leading to small numbers of subjects analyzed
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Benatar
Organization: University Of Miami
Phone: 305-243-6480
EMail: MBenatar@med.miami.edu
Layout table for additonal information
Responsible Party: Michael Benatar, University of Miami
ClinicalTrials.gov Identifier: NCT00995722     History of Changes
Other Study ID Numbers: FD-R-03710-01
First Submitted: October 14, 2009
First Posted: October 15, 2009
Results First Submitted: September 28, 2015
Results First Posted: November 2, 2015
Last Update Posted: June 2, 2017