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BeatMG: Phase II Trial of Rituximab In Myasthenia Gravis

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ClinicalTrials.gov Identifier: NCT02110706
Recruitment Status : Completed
First Posted : April 10, 2014
Results First Posted : October 2, 2018
Last Update Posted : March 6, 2020
Sponsor:
Collaborator:
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
Yale University

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Single Group Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Myasthenia Gravis
Interventions Drug: Rituximab
Drug: Placebo
Enrollment 52
Recruitment Details  
Pre-assignment Details 68 study participants were consented and assessed for eligibility. 14 participants were ineligible. 2 participants declined. 52 study participants were randomized.
Arm/Group Title Rituximab Placebo Group
Hide Arm/Group Description - Treatment group received two cycles of rituximab (375mg/m2 iv), separated by 6 months. Each cycle defined as one infusion per week for four consecutive weeks. For the main study, participants were followed for 52 weeks. Study participants had clinical evaluations performed by a blinded evaluator at baseline and every 4 weeks thereafter. - Placebo group received infusion containing only vehicle components of rituximab solution. Infusion was done in 2 cycles, separated by 6 months. Each cycle defined as one infusion per week for four consecutive weeks. For the main study, participants were followed for 52 weeks. Study participants had clinical evaluations performed by a blinded evaluator at baseline and every 4 weeks thereafter.
Period Title: Overall Study
Started 25 27
No. Completing Study Through Week 52 23 24
Completed [1] 20 23
Not Completed 5 4
Reason Not Completed
Adverse Event             2             3
Patients who didn't receive 2nd infusion             3             1
[1]
No. of participants who completed two-cycle rituximab/placebo treatment
Arm/Group Title Rituximab Placebo Total
Hide Arm/Group Description - Treatment group received two cycles of rituximab (375mg/m2 iv), separated by 6 months. Each cycle defined as one infusion per week for four consecutive weeks. For the main study, participants were followed for 52 weeks. Study participants had clinical evaluations performed by a blinded evaluator at baseline and every 4 weeks thereafter. - Placebo group received infusion containing only vehicle components of rituximab solution. Infusion was done in 2 cycles, separated by 6 months. Each cycle defined as one infusion per week for four consecutive weeks. For the main study, participants were followed for 52 weeks. Study participants had clinical evaluations performed by a blinded evaluator at baseline and every 4 weeks thereafter. Total of all reporting groups
Overall Number of Baseline Participants 25 27 52
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 25 participants 27 participants 52 participants
53.2  (17.5) 56.8  (17.0) 55.1  (17.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 25 participants 27 participants 52 participants
Female
11
  44.0%
12
  44.4%
23
  44.2%
Male
14
  56.0%
15
  55.6%
29
  55.8%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Race and ethnicity Number Analyzed 25 participants 27 participants 52 participants
Asian
0
   0.0%
1
   3.7%
1
   1.9%
African American
2
   8.0%
9
  33.3%
11
  21.2%
Hispanic
3
  12.0%
2
   7.4%
5
   9.6%
Non-Hispanic white
20
  80.0%
15
  55.6%
35
  67.3%
Baseline Prednisone Dose  
Mean (Standard Deviation)
Unit of measure:  Mg/day
Number Analyzed 25 participants 27 participants 52 participants
23  (11.2) 21.3  (8.3) 22.1  (9.7)
Baseline Myasthenia Gravis Composite (MGC)   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 25 participants 27 participants 52 participants
11.1  (6.1) 8.5  (4.0) 9.8  (5.2)
[1]
Measure Description: The Myasthenia Gravis Composite (MGC) scale consists of test items from the MG-ADL (Myasthenia Gravis Activities of Daily Living) scale and the QMG (Quantitative Myasthenia Gravis Scale) that measure symptoms and signs of MG, with weighted response options. The minimum score is 0, and the maximum score is 50. Higher scores correlate with clinical worsening of the disease.
Baseline Quantitative Myasthenia Gravis (QMG)   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 25 participants 27 participants 52 participants
11.0  (5.1) 9.2  (3.9) 10.1  (4.5)
[1]
Measure Description: The Quantitative Myasthenia Gravis Score (QMG) is a commonly used objective outcome measure in myasthenia gravis (MG) comprising 13 items measuring ocular, bulbar, extremity fatigue/strength, and respiratory function (forced vital capacity), each with a possible score from 0 to 3, and a maximum possible of 39 points, where a higher score indicates more severe disease.
Baseline MG-Activities of Daily Living Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 25 participants 27 participants 52 participants
5.8  (3.6) 4.0  (3.4) 4.9  (3.6)
[1]
Measure Description: This 8 point scale with a maximum score of 24 and a minimum of 0 assesses the subject's ability to perform daily activities and can be performed in approximately 5 minutes. A higher score indicates more severe disease.
Baseline MG-Quality of Life (MG-QOL) score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 25 participants 27 participants 52 participants
22.7  (14.1) 17.7  (10.6) 20.1  (12.5)
[1]
Measure Description: The subject completes the 15-question MG-QOL questionnaire and reports the effect of MG on their quality of life. The MG-QOL should be administered prior to other outcomes evaluations at each visit.The maximum score is 60 and the minimum is 0. A higher score indicates more severe disease.
Baseline MGFA Clinical Classification Grade   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 25 participants 27 participants 52 participants
Class I
0
   0.0%
1
   3.7%
1
   1.9%
Class II
15
  60.0%
16
  59.3%
31
  59.6%
Class III
9
  36.0%
9
  33.3%
18
  34.6%
Class IV
1
   4.0%
1
   3.7%
2
   3.8%
[1]
Measure Description: Class I- Any ocular muscle weakness, may have weakness of eye closure, all other muscle strength is normal. Class II - Mild weakness affecting other than ocular muscles, may also have ocular muscle weakness of any severity. Class III - Moderate weakness affecting other than ocular muscles, may also have ocular muscle weakness of any severity. Class IV - Severe weakness affecting other than ocular muscles, may also have ocular muscle weakness of any severity. A higher grade is indicative of a worse outcome.
Thymectomy  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 25 participants 27 participants 52 participants
8
  32.0%
4
  14.8%
12
  23.1%
1.Primary Outcome
Title Steroid Sparing Effect
Hide Description Percent of subjects that achieve a ≥ 75% reduction in mean daily prednisone dose in the 4 weeks prior to week 52 and have clinical improvement or no significant worsening of symptoms (≤ 2 point increase in MGC score) as compared to 4-week period prior to randomization and initiation of treatment.
Time Frame 4 weeks prior baseline and 4 weeks prior to week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to treat participants
Arm/Group Title Rituximab Placebo
Hide Arm/Group Description:
- Treatment group received two cycles of rituximab (375mg/m2 iv), separated by 6 months. Each cycle defined as one infusion per week for four consecutive weeks. For the main study, participants were followed for 52 weeks. Study participants had clinical evaluations performed by a blinded evaluator at baseline and every 4 weeks thereafter.
- Placebo group received infusion containing only vehicle components of rituximab solution. Infusion was done in 2 cycles, separated by 6 months. Each cycle defined as one infusion per week for four consecutive weeks. For the main study, participants were followed for 52 weeks. Study participants had clinical evaluations performed by a blinded evaluator at baseline and every 4 weeks thereafter.
Overall Number of Participants Analyzed 25 27
Measure Type: Count of Participants
Unit of Measure: Participants
15
  60.0%
15
  55.6%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab, Placebo
Comments

This futility design tests the following hypothesis:

H0: Rituximab improves outcome by at least 30% compared to placebo (pR - pP ≥ 0.30 - not futile) versus HA: Rituximab does not improve outcome by at least 30% compared to placebo (pR - pP < 0.30 - futile)

Type of Statistical Test Other
Comments A futility (non-superiority) design is a screening tool to identify whether agents should be candidates for phase III trials while minimizing costs/sample size If "futility" is declared, results would imply not cost effective to conduct a future phase III clinical trial If "futility" is not declared, suggests that there could be a clinically meaningful effect - supports exploration in a larger, phase III trial
Statistical Test of Hypothesis P-Value 0.03
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.14
Confidence Interval (1-Sided) 90%
2.41
Estimation Comments [Not Specified]
2.Primary Outcome
Title Safety:Percentage of Study Participants With Treatment-related Adverse Experiences
Hide Description Evaluate treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to treat participants
Arm/Group Title Rituximab Placebo
Hide Arm/Group Description:
- Treatment group received two cycles of rituximab (375mg/m2 iv), separated by 6 months.Each cycle defined as one infusion per week for four consecutive weeks.For the main study, participants were followed for 52 weeks.Study participants had clinical evaluations performed by a blinded evaluator at baseline and every 4 weeks thereafter.

- Placebo group received infusion containing only vehicle components of rituximab solution. Infusion was done in 2 cycles

, separated by 6 months. Each cycle defined as one infusion per week for four consecutive weeks. For the main study, participants were followed for 52 weeks. Study participants had clinical evaluations performed by a blinded evaluator at baseline and every 4 weeks thereafter.

Overall Number of Participants Analyzed 25 27
Measure Type: Count of Participants
Unit of Measure: Participants
% of participants with treatment related AEs
19
  76.0%
22
  81.5%
% participants with treatment related SAEs
6
  24.0%
8
  29.6%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab, Placebo
Comments % of study participants with treatment related AEs
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.63
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.72
Confidence Interval (2-Sided) 90%
0.23 to 2.21
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Rituximab, Placebo
Comments % study participants with treatment related SAEs
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.65
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.75
Confidence Interval (2-Sided) 90%
0.27 to 2.11
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change in Myasthenia Gravis Composite (MGC) Scores From Baseline to Week 52
Hide Description Evaluate whether there is a trend towards clinical benefit at end of 52 week treatment period, as measured by mean change in the MGC score, an MG-specific clinical outcomes scale used as endpoint in prior MG clinical trials. The Myasthenia Gravis Composite (MGC) scale consists of test items from the MG-ADL (Myasthenia Gravis Activities of Daily Living) scale and the QMG (Quantitative Myasthenia Gravis Scale) that measure symptoms and signs of MG, with weighted response options. The minimum score is 0, and the maximum score is 50. Higher scores correlate with clinical worsening of the disease.
Time Frame baseline and 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to treat participants
Arm/Group Title Rituximab Placebo
Hide Arm/Group Description:
- Treatment group received two cycles of rituximab (375mg/m2 iv), separated by 6 months. Each cycle defined as one infusion per week for four consecutive weeks. For the main study, participants were followed for 52 weeks. Study participants had clinical evaluations performed by a blinded evaluator at baseline and every 4 weeks thereafter.
- Placebo group received infusion containing only vehicle components of rituximab solution. Infusion was done in 2 cycles, separated by 6 months. Each cycle defined as one infusion per week for four consecutive weeks. For the main study, participants were followed for 52 weeks. Study participants had clinical evaluations performed by a blinded evaluator at baseline and every 4 weeks thereafter.
Overall Number of Participants Analyzed 25 27
Mean (Standard Deviation)
Unit of Measure: score on a scale
-5.7  (7.26) -4.0  (4.10)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab, Placebo
Comments This objective was assessed longitudinally by comparing the final score at the end of the study to the score obtained at baseline. The outcome was defined as the change from baseline to week 52 in the MGC. This hypothesis was assessed using a linear regression model, adjusted for differences in baseline MGC scores.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.93
Comments [Not Specified]
Method Regression, Linear
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.11
Confidence Interval (1-Sided) 90%
2.02
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change in Quantitative Myasthenia Gravis(QMG) Scores From Baseline to Week 52
Hide Description Evaluate whether there is a trend towards clinical benefit at end of 52 week treatment period, as measured by the mean change in the QMG score - a specific clinical outcome scale used as endpoint in prior MG clinical trials. The Quantitative Myasthenia Gravis Score (QMG) is a commonly used objective outcome measure in myasthenia gravis (MG) comprising 13 items, each with a possible score from 0 to 3, and a maximum possible of 39 points, where a higher score indicates more severe disease.
Time Frame baseline and 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to treat participants
Arm/Group Title Rituximab Placebo
Hide Arm/Group Description:
- Treatment group received two cycles of rituximab (375mg/m2 iv), separated by 6 months.Each cycle defined as one infusion per week for four consecutive weeks.For the main study, participants were followed for 52 weeks.Study participants had clinical evaluations performed by a blinded evaluator at baseline and every 4 weeks thereafter.

- Placebo group received infusion containing only vehicle components of rituximab solution. Infusion was done in 2 cycles

, separated by 6 months. Each cycle defined as one infusion per week for four consecutive weeks. For the main study, participants were followed for 52 weeks. Study participants had clinical evaluations performed by a blinded evaluator at baseline and every 4 weeks thereafter.

Overall Number of Participants Analyzed 25 27
Mean (Standard Deviation)
Unit of Measure: score on a scale
-3.95  (5.43) -1.70  (3.91)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab, Placebo
Comments This objective was assessed longitudinally by comparing the final score at the end of the study to the score obtained at baseline. The outcome was defined as the change from baseline to week 52 in the QMG. This hypothesis was assessed using a linear regression model, adjusted for differences in baseline QMG scores.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.39
Comments [Not Specified]
Method Regression, Linear
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.09
Confidence Interval (1-Sided) 90%
1.03
Estimation Comments [Not Specified]
Time Frame 52 weeks
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Rituximab Placebo Group
Hide Arm/Group Description - Treatment group received two cycles of rituximab (375mg/m2 iv), separated by 6 months. Each cycle defined as one infusion per week for four consecutive weeks. For the main study, participants were followed for 52 weeks. Study participants had clinical evaluations performed by a blinded evaluator at baseline and every 4 weeks thereafter. - Placebo group received infusion containing only vehicle components of rituximab solution. Infusion was done in 2 cycles, separated by 6 months. Each cycle defined as one infusion per week for four consecutive weeks. For the main study, participants were followed for 52 weeks. Study participants had clinical evaluations performed by a blinded evaluator at baseline and every 4 weeks thereafter.
All-Cause Mortality
Rituximab Placebo Group
Affected / at Risk (%) Affected / at Risk (%)
Total   0/25 (0.00%)      0/27 (0.00%)    
Hide Serious Adverse Events
Rituximab Placebo Group
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   9/25 (36.00%)      14/27 (51.85%)    
Blood and lymphatic system disorders     
Anaemia  2  0/25 (0.00%)  0 1/27 (3.70%)  1
Leukopenia  2  1/25 (4.00%)  1 0/27 (0.00%)  0
Cardiac disorders     
Cardiac failure congestive  2  0/25 (0.00%)  0 1/27 (3.70%)  1
Coronary artery disease  2  0/25 (0.00%)  0 1/27 (3.70%)  2
Gastrointestinal disorders     
Colonic obstruction  2  0/25 (0.00%)  0 1/27 (3.70%)  1
Diverticulum intestinal  2  0/25 (0.00%)  0 1/27 (3.70%)  1
Small intestinal obstruction  2  0/25 (0.00%)  0 1/27 (3.70%)  1
General disorders     
Chest pain  2  0/25 (0.00%)  0 1/27 (3.70%)  1
Pyrexia  2  0/25 (0.00%)  0 1/27 (3.70%)  1
Immune system disorders     
Hypersensitivity  2  1/25 (4.00%)  1 0/27 (0.00%)  0
Infections and infestations     
Abscess neck  2  0/25 (0.00%)  0 1/27 (3.70%)  2
Cellulitis  2  0/25 (0.00%)  0 1/27 (3.70%)  1
Clostridium difficile colitis  2  0/25 (0.00%)  0 1/27 (3.70%)  1
Diverticulitis  2  1/25 (4.00%)  1 0/27 (0.00%)  0
Pneumonia  2  0/25 (0.00%)  0 1/27 (3.70%)  1
Sepsis  2  0/25 (0.00%)  0 1/27 (3.70%)  1
Septic shock  2  1/25 (4.00%)  1 0/27 (0.00%)  0
Injury, poisoning and procedural complications     
Spinal compression fracture  2  0/25 (0.00%)  0 1/27 (3.70%)  1
Vascular pseudoaneurysm  2  1/25 (4.00%)  1 0/27 (0.00%)  0
Investigations     
Platelet count decreased  2  1/25 (4.00%)  1 0/27 (0.00%)  0
Metabolism and nutrition disorders     
Hyperglycaemia  2  1/25 (4.00%)  1 0/27 (0.00%)  0
Hyperkalaemia  2  0/25 (0.00%)  0 1/27 (3.70%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Prostate cancer  2  0/25 (0.00%)  0 1/27 (3.70%)  1
Nervous system disorders     
Worsening of MG  1  1/25 (4.00%)  1 3/27 (11.11%)  4
Psychiatric disorders     
Psychotic disorder  2  1/25 (4.00%)  1 0/27 (0.00%)  0
Renal and urinary disorders     
Nephrolithiasis  2  1/25 (4.00%)  1 0/27 (0.00%)  0
Reproductive system and breast disorders     
Menorrhagia  2  1/25 (4.00%)  1 0/27 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  2  0/25 (0.00%)  0 1/27 (3.70%)  1
Pulmonary embolism  2  1/25 (4.00%)  1 1/27 (3.70%)  1
Surgical and medical procedures     
Micrographic skin surgery  2  0/25 (0.00%)  0 1/27 (3.70%)  1
Vascular disorders     
Hypotension  2  1/25 (4.00%)  1 0/27 (0.00%)  0
Thrombosis  2  0/25 (0.00%)  0 1/27 (3.70%)  1
Venous thrombosis limb  2  1/25 (4.00%)  1 0/27 (0.00%)  0
1
Term from vocabulary, MedRA
2
Term from vocabulary, MedDRA (19.0)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Rituximab Placebo Group
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   25/25 (100.00%)      26/27 (96.30%)    
Ear and labyrinth disorders     
Vertigo  1  2/25 (8.00%)  2 0/27 (0.00%)  0
Eye disorders     
Vision blurred  1  1/25 (4.00%)  1 2/27 (7.41%)  2
Gastrointestinal disorders     
Abdominal pain  1  3/25 (12.00%)  3 2/27 (7.41%)  2
Constipation  1  1/25 (4.00%)  1 2/27 (7.41%)  2
Diarrhoea  1  3/25 (12.00%)  4 2/27 (7.41%)  2
Nausea  1  2/25 (8.00%)  3 6/27 (22.22%)  10
Vomiting  1  2/25 (8.00%)  2 2/27 (7.41%)  2
Pyrexia  1  2/25 (8.00%)  2 1/27 (3.70%)  1
General disorders     
Fatigue  1  3/25 (12.00%)  3 8/27 (29.63%)  9
Influenza like illness  1  3/25 (12.00%)  4 2/27 (7.41%)  2
Oedema peripheral  1  1/25 (4.00%)  1 2/27 (7.41%)  3
Injection site reaction  1  2/25 (8.00%)  3 0/27 (0.00%)  0
Immune system disorders     
Hypersensitivity  1  3/25 (12.00%)  3 0/27 (0.00%)  0
Infections and infestations     
Bronchitis  1  1/25 (4.00%)  1 3/27 (11.11%)  4
Cellulitis  1  2/25 (8.00%)  2 1/27 (3.70%)  1
Gastroenteritis  1  0/25 (0.00%)  0 3/27 (11.11%)  3
Oral candidiasis  1  1/25 (4.00%)  1 2/27 (7.41%)  2
Rhinitis  1  2/25 (8.00%)  3 2/27 (7.41%)  2
Sinusitis  1  2/25 (8.00%)  2 3/27 (11.11%)  4
Upper respiratory tract infection  1  9/25 (36.00%)  12 5/27 (18.52%)  5
Urinary tract infection  1  2/25 (8.00%)  2 3/27 (11.11%)  5
Pneumonia  1  2/25 (8.00%)  2 0/27 (0.00%)  0
Fungal skin infection  1  2/25 (8.00%)  2 0/27 (0.00%)  0
Injury, poisoning and procedural complications     
Contusion  1  2/25 (8.00%)  2 1/27 (3.70%)  1
Fall  1  0/25 (0.00%)  0 3/27 (11.11%)  3
Neck pain  1  0/25 (0.00%)  0 2/27 (7.41%)  2
Investigations     
Weight increased  1  0/25 (0.00%)  0 2/27 (7.41%)  2
Metabolism and nutrition disorders     
Dehydration  1  2/25 (8.00%)  2 1/27 (3.70%)  1
Musculoskeletal and connective tissue disorders     
Arthralgia  1  6/25 (24.00%)  6 10/27 (37.04%)  15
Back pain  1  2/25 (8.00%)  2 9/27 (33.33%)  11
Muscle spasms  1  3/25 (12.00%)  3 1/27 (3.70%)  1
Muscular weakness  1  4/25 (16.00%)  4 3/27 (11.11%)  4
Musculoskeletal pain  1  3/25 (12.00%)  3 1/27 (3.70%)  1
Myalgia  1  1/25 (4.00%)  2 4/27 (14.81%)  5
Pain in extremity  1  3/25 (12.00%)  3 4/27 (14.81%)  9
Nervous system disorders     
Dizziness  1  3/25 (12.00%)  3 1/27 (3.70%)  1
Headache  1  8/25 (32.00%)  11 7/27 (25.93%)  13
Paraesthesia  2  0/25 (0.00%)  0 5/27 (18.52%)  7
Tremor  1  2/25 (8.00%)  3 3/27 (11.11%)  4
Renal and urinary disorders     
Urinary retention  1  0/25 (0.00%)  0 2/27 (7.41%)  2
Respiratory, thoracic and mediastinal disorders     
Cough  1  0/25 (0.00%)  0 3/27 (11.11%)  3
Dysphonia  1  0/25 (0.00%)  0 2/27 (7.41%)  3
Dyspnoea  1  2/25 (8.00%)  2 1/27 (3.70%)  1
Nasal congestion  1  2/25 (8.00%)  2 1/27 (3.70%)  1
Oropharyngeal pain  1  3/25 (12.00%)  3 0/27 (0.00%)  0
Respiratory tract congestion  1  0/25 (0.00%)  0 2/27 (7.41%)  2
Rhinorrhoea  1  3/25 (12.00%)  3 0/27 (0.00%)  0
Skin and subcutaneous tissue disorders     
Rash  1  3/25 (12.00%)  3 2/27 (7.41%)  2
Rash maculo-papular  1  1/25 (4.00%)  1 3/27 (11.11%)  3
Skin lesion  1  0/25 (0.00%)  0 2/27 (7.41%)  3
Surgical and medical procedures     
Cataract operation  1  0/25 (0.00%)  0 2/27 (7.41%)  2
Vascular disorders     
Hypotension  1  2/25 (8.00%)  2 0/27 (0.00%)  0
1
Term from vocabulary, MedDRA (19.0)
2
Term from vocabulary, MedRA
Indicates events were collected by systematic assessment
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: Dr. Richard Nowak, MD,MS
Organization: Yale School of Medicine
Phone: 203-785-4085
EMail: richard.nowak@yale.edu
Layout table for additonal information
Responsible Party: Yale University
ClinicalTrials.gov Identifier: NCT02110706    
Other Study ID Numbers: 1401013253-0
1U01NS084495-01A1 ( U.S. NIH Grant/Contract )
U01NS077179-01 ( U.S. NIH Grant/Contract )
U01NS077352 ( U.S. NIH Grant/Contract )
First Submitted: April 7, 2014
First Posted: April 10, 2014
Results First Submitted: July 31, 2018
Results First Posted: October 2, 2018
Last Update Posted: March 6, 2020