Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Clinical Efficacy Trial of Mexiletine for Myotonic Dystrophy Type 1

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: NCT01406873
Recruitment Status : Completed
First Posted : August 1, 2011
Results First Posted : March 29, 2018
Last Update Posted : June 19, 2018
Sponsor:
Information provided by (Responsible Party):
Chad Heatwole, University of Rochester

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Myotonic Dystrophy
Interventions Drug: Mexiletine
Drug: Placebo
Enrollment 42
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Mexiletine Placebo
Hide Arm/Group Description This group received 150 mg/kg Mexiletine capsules taken by mouth, three times daily for 6 months This group received 150 mg/kg placebo capsules taken by mouth, three times daily for 6 months
Period Title: Overall Study
Started 21 21
Completed 20 20
Not Completed 1 1
Reason Not Completed
Withdrawal by Subject             1             1
Arm/Group Title Mexiletine Placebo Total
Hide Arm/Group Description This group received 150 mg/kg Mexiletine capsules taken by mouth, three times daily for 6 months This group received 150 mg/kg placebo capsules taken by mouth, three times daily for 6 months Total of all reporting groups
Overall Number of Baseline Participants 21 21 42
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 21 participants 21 participants 42 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
21
 100.0%
21
 100.0%
42
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 21 participants 21 participants 42 participants
42.05  (11.54) 38.14  (9.78) 40.10  (10.75)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 21 participants 21 participants 42 participants
Female
17
  81.0%
12
  57.1%
29
  69.0%
Male
4
  19.0%
9
  42.9%
13
  31.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 21 participants 21 participants 42 participants
Hispanic or Latino
1
   4.8%
1
   4.8%
2
   4.8%
Not Hispanic or Latino
20
  95.2%
20
  95.2%
40
  95.2%
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 21 participants 21 participants 42 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
0
   0.0%
0
   0.0%
0
   0.0%
White
20
  95.2%
20
  95.2%
40
  95.2%
More than one race
1
   4.8%
1
   4.8%
2
   4.8%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 21 participants 21 participants 42 participants
21
 100.0%
21
 100.0%
42
 100.0%
1.Primary Outcome
Title Mean Change From Baseline in Ambulation Using the 6 Minute Walk Distance
Hide Description During this assessment, participants were asked to walk as far as they could back and forth on a fixed 20 meter route for 6 minutes. The total distance walked during the 6 minutes was recorded in meters. Change from baseline was defined as the difference between the average 6 minute walk distance at baseline and the average 6 minute walk distance at 6 months.
Time Frame Baseline to 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT) population was defined as all participants who were randomized to the study, received at least one dose of study medication and have post-baseline efficacy assessment. Follow-up data was not collected on one participant in the mexiletine arm due to a broken foot.
Arm/Group Title Mexiletine Placebo
Hide Arm/Group Description:
Mean Change from Baseline in Ambulation using the 6 Minute Walk Test in Patients who Received Mexiletine (150 mg/kg capsules taken by mouth, three times daily for 6 months)
Mean Change from Baseline in Ambulation using the 6 Minute Walk Test in Patients who Received Placebo (150 mg/kg capsules taken by mouth, three times daily for 6 months)
Overall Number of Participants Analyzed 19 20
Mean (Standard Deviation)
Unit of Measure: Meters
17.44  (39.84) 7.25  (38.93)
2.Secondary Outcome
Title Percentage of Participants That Had a Dose Reduction or a Study Drug Withdrawal or Suspension Over 6 Months
Hide Description Adverse events were monitored at the three in-person evaluations (Months 0, 3, and 6), at telephone evaluations every 2 weeks, and via patient-completed side effect diaries. The study investigators and safety monitoring committee reviewed adverse events and made decisions regarding drug withdrawals, suspensions, and dose reductions as needed.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT) population was defined as all participants who were randomized to the study, received at least one dose of study medication and have post-baseline efficacy assessment.
Arm/Group Title Mexiletine Placebo
Hide Arm/Group Description:
Percentage of Participants that had a dose Reduction or a Study Drug Withdrawal or Suspension for Patients who Received Mexiletine (150 mg/kg capsules taken by mouth, three times daily for 6 months)
Percentage of Participants that had a dose Reduction or a Study Drug Withdrawal or Suspension for Patients who Received Placebo (150 mg/kg capsules taken by mouth, three times daily for 6 months)
Overall Number of Participants Analyzed 20 20
Measure Type: Count of Participants
Unit of Measure: Participants
Study Drug Withdrawal
2
  10.0%
0
   0.0%
Study Drug Dose Reduction
1
   5.0%
0
   0.0%
Study Drug Temporary Suspension
1
   5.0%
0
   0.0%
3.Secondary Outcome
Title Mean Change From Baseline in Quantitative Measure of Hand Grip Myotonia
Hide Description Relaxation time of the long finger flexor muscles of the right hand after a maximum voluntary isometric contraction performed in a standardized fixed position of the right arm elbow/wrist/hand. Relaxation time for this measurement is defined as the time to relax from 90% to 5% of the maximum isometric force of contraction of the hand (the first of 6 serial contractions averaged over two consecutive trials performed 10 minutes apart).
Time Frame Baseline to 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT) population was defined as all participants who were randomized to the study, received at least one dose of study medication, and have post-baseline efficacy assessment at 6 months. Data was not analyzable on 3 people in the placebo arm.
Arm/Group Title Mexiletine Placebo
Hide Arm/Group Description:
Mean Change from Baseline in Quantitative Measure of Hand Grip Myotonia for Patients who Received Mexiletine (150 mg/kg capsules taken by mouth, three times daily for 6 months)
Mean Change from Baseline in Quantitative Measure of Hand Grip Myotonia for Patients who Received Placebo (150 mg/kg capsules taken by mouth, three times daily for 6 months)
Overall Number of Participants Analyzed 20 17
Mean (Standard Deviation)
Unit of Measure: Seconds
-1.01  (1.78) 0.43  (1.53)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Mexiletine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.01
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
4.Secondary Outcome
Title Mean Change From Baseline in Manual Muscle Testing (MMT) Score
Hide Description Manual muscle testing was performed on 26 muscle groups (shoulder abductors, elbow flexors, wrist flexors, wrist extensors, hip flexors, knee extensors, hip extensors, knee flexors, hip abductors, elbow extensors, ankle dorsiflexors, and plantar flexors on the right and left plus neck extensor and neck flexors). The muscles were tested in various positions including sitting, supine, prone, and side lying and each graded on a modification of the Medical Research Council (MRC) scale of 0 to 5 (5 representing normal strength). Average MMT score is derived by averaging the individual MMT scores across the 26 individual muscles.
Time Frame Baseline to 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT) population was defined as all participants who were randomized to the study, received at least one dose of study medication and have post-baseline efficacy assessment.
Arm/Group Title Mexiletine Placebo
Hide Arm/Group Description:
Mean Change from Baseline in Manual Muscle Testing (MMT) Score for Patients who Received Mexiletine (150 mg/kg capsules taken by mouth, three times daily for 6 months)
Mean Change from Baseline in Manual Muscle Testing (MMT) Score for Patients who Received Placebo (150 mg/kg capsules taken by mouth, three times daily for 6 months)
Overall Number of Participants Analyzed 20 20
Mean (Standard Deviation)
Unit of Measure: Units on a scale
0.05  (0.23) -0.06  (0.12)
5.Secondary Outcome
Title Mean Change From Baseline in PR, QRS, and QTc Intervals, and Average Minimum Heart Rate (HR) Via Electrocardiogram (ECG) Monitoring
Hide Description PR, QRS, and QTc intervals as well as average minimum heart rate (HR) were obtained through standard 12 lead electrocardiograms (ECGs). Values were computer generated and verified by the study investigator and study cardiologist.
Time Frame Baseline to 6 Months
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT) population was defined as all participants who were randomized to the study, received at least one dose of study medication and have post-baseline efficacy assessment.
Arm/Group Title Mexiletine Placebo
Hide Arm/Group Description:
This group received 150 mg/kg Mexiletine capsules taken by mouth, three times daily for 6 months
This group received 150 mg/kg placebo capsules taken by mouth, three times daily for 6 months
Overall Number of Participants Analyzed 20 20
Mean (Standard Error)
Unit of Measure: Milliseconds
PR Interval Number Analyzed 20 participants 18 participants
11.35  (38.08) 8.89  (13.20)
QRS Interval Number Analyzed 20 participants 20 participants
0.70  (11.50) 1.00  (6.37)
QTc Interval Number Analyzed 20 participants 20 participants
-4.40  (23.37) -1.55  (14.75)
Average Minimum Heart Rate Number Analyzed 20 participants 20 participants
0.65  (4.57) -0.25  (5.72)
6.Secondary Outcome
Title Mean Change From Baseline in Patient-Reported Disease Burden and Quality of Life
Hide Description
  • The Myotonic Dystrophy Health Index (MDHI) is a validated disease-specific measure of patient-reported disease burden. The MDHI total score is a weighted average derived from 17 subscales. MDHI total scores range form 0-100 with 0 representing no patient-reported disease burden and 100 representing the most severe patient-reported disease burden.
  • The Individualized Neuromuscular Quality of Life Questionnaire (INQoL) is a measure of quality of life in neuromuscular disease. The INQoL summary score is a weighted average made up of 5 sub-domains. Scores range from 0-100, and can be interpreted as the percent of maximal detrimental impact on quality of life with higher scores indicating more detrimental impact.
  • The 36-Item Short Form Survey (SF-36) is a generic measure of quality of life across 8 domains. Two summary metrics are produced from the 8 domains, ranging from 0-100% with lower scores representing worse levels of functioning.
Time Frame Baseline to 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat (ITT) population was defined as all participants who were randomized to the study, received at least one dose of study medication and have post-baseline efficacy assessment.
Arm/Group Title Mexiletine Placebo
Hide Arm/Group Description:
Mean Change from Baseline in Patient-Reported Disease Burden and Quality of Life for Patients who Received Mexiletine (150 mg/kg capsules taken by mouth, three times daily for 6 months)
Mean Change from Baseline in Patient-Reported Disease Burden and Quality of Life for Patients who Received Placebo (150 mg/kg capsules taken by mouth, three times daily for 6 months)
Overall Number of Participants Analyzed 20 20
Mean (Standard Deviation)
Unit of Measure: Units on a scale
INQoL Number Analyzed 20 participants 20 participants
5.11  (14.80) 2.33  (12.84)
MDHI Number Analyzed 20 participants 20 participants
0.01  (7.75) -1.10  (10.02)
SF-36 Physical Component Summary Number Analyzed 20 participants 19 participants
-1.73  (7.12) -1.35  (7.22)
SF-36 Mental Component Summary Number Analyzed 20 participants 19 participants
-0.62  (9.01) -0.79  (9.22)
Time Frame Adverse event data were collected for 7 months. This period included 6 months (starting from randomization) on study drug (mexiletine vs. placebo) and 1 month post discontinuation of study drug.
Adverse Event Reporting Description 2 subjects experienced study related AEs prior to randomization; both were in the mexiletine arm and both AEs were 'Skin and subcutaneous tissue disorders - Other, rash' and related to study procedures (where Holter monitor electrodes were placed). They are not included in the AE data displayed.
 
Arm/Group Title Mexiletine Placebo
Hide Arm/Group Description Adverse Events for Patients who Received Mexiletine (150 mg/kg capsules taken by mouth, three times daily for 6 months) Adverse Events for Patients who Received Placebo (150 mg/kg capsules taken by mouth, three times daily for 6 months)
All-Cause Mortality
Mexiletine Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/21 (0.00%)      0/21 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Mexiletine Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/21 (4.76%)      1/21 (4.76%)    
Injury, poisoning and procedural complications     
Fracture  1  0/21 (0.00%)  0 1/21 (4.76%)  1
Nervous system disorders     
Stroke  1  1/21 (4.76%)  1 0/21 (0.00%)  0
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 4%
Mexiletine Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   21/21 (100.00%)      20/21 (95.24%)    
Cardiac disorders     
Cardiac disorders - Other, increased PVCs  1  1/21 (4.76%)  1 0/21 (0.00%)  0
Chest pain - cardiac  1  1/21 (4.76%)  2 1/21 (4.76%)  2
Ear and labyrinth disorders     
Ear pain  1  0/21 (0.00%)  0 1/21 (4.76%)  1
Tinnitus  1  1/21 (4.76%)  2 0/21 (0.00%)  0
Eye disorders     
Blurred vision  1  0/21 (0.00%)  0 1/21 (4.76%)  1
Conjunctivitis  1  1/21 (4.76%)  1 0/21 (0.00%)  0
Gastrointestinal disorders     
Abdominal distension  1  1/21 (4.76%)  1 0/21 (0.00%)  0
Abdominal pain  1  0/21 (0.00%)  0 2/21 (9.52%)  2
Bloating  1  1/21 (4.76%)  1 0/21 (0.00%)  0
Constipation  1  2/21 (9.52%)  2 1/21 (4.76%)  1
Diarrhea  1  3/21 (14.29%)  4 2/21 (9.52%)  4
Dyspepsia  1  7/21 (33.33%)  7 2/21 (9.52%)  2
Dysphagia  1  2/21 (9.52%)  2 1/21 (4.76%)  1
Esophageal pain  1  1/21 (4.76%)  2 0/21 (0.00%)  0
Flatulence  1  1/21 (4.76%)  1 0/21 (0.00%)  0
Gastrointestinal disorders - Other, gastric distension  1  1/21 (4.76%)  1 0/21 (0.00%)  0
Gastrointestinal disorders - Other, viral gastroenteritis  1  1/21 (4.76%)  1 1/21 (4.76%)  1
Nausea  1  7/21 (33.33%)  8 5/21 (23.81%)  5
Stomach pain  1  3/21 (14.29%)  3 3/21 (14.29%)  3
Vomiting  1  3/21 (14.29%)  4 1/21 (4.76%)  1
General disorders     
Fatigue  1  0/21 (0.00%)  0 2/21 (9.52%)  2
Flu like symptoms  1  12/21 (57.14%)  21 15/21 (71.43%)  28
Pain  1  3/21 (14.29%)  3 1/21 (4.76%)  3
Hepatobiliary disorders     
Hepatobiliary disorders - Other, elevated GGT  1  1/21 (4.76%)  1 0/21 (0.00%)  0
Infections and infestations     
Bladder infection  1  1/21 (4.76%)  1 0/21 (0.00%)  0
Infections and infestations - Other, elevated eosinophils  1  0/21 (0.00%)  0 1/21 (4.76%)  1
Sinusitis  1  1/21 (4.76%)  1 2/21 (9.52%)  2
Upper respiratory infection  1  1/21 (4.76%)  1 0/21 (0.00%)  0
Bronchial infection  1  0/21 (0.00%)  0 2/21 (9.52%)  2
Injury, poisoning and procedural complications     
Bruising  1  1/21 (4.76%)  1 0/21 (0.00%)  0
Burn  1  1/21 (4.76%)  1 1/21 (4.76%)  1
Fall  1  5/21 (23.81%)  7 2/21 (9.52%)  3
Fracture  1  1/21 (4.76%)  1 0/21 (0.00%)  0
Injury, poisoning and procedural complications - Other, cut finger  1  0/21 (0.00%)  0 1/21 (4.76%)  1
Injury, poisoning and procedural complications - Other, tendinitis  1  0/21 (0.00%)  0 1/21 (4.76%)  1
Injury, poisoning and procedural complications - Other, wrist sprain  1  1/21 (4.76%)  1 0/21 (0.00%)  0
Metabolism and nutrition disorders     
Metabolism and nutrition disorders - Other, extreme thirst  1  0/21 (0.00%)  0 1/21 (4.76%)  1
Musculoskeletal and connective tissue disorders     
Back pain  1  2/21 (9.52%)  2 2/21 (9.52%)  4
Musculoskeletal and connective tissue disorder - Other, heel spur  1  0/21 (0.00%)  0 1/21 (4.76%)  1
Musculoskeletal and connective tissue disorder - Other, pelvic pain  1  1/21 (4.76%)  1 0/21 (0.00%)  0
Neck pain  1  0/21 (0.00%)  0 1/21 (4.76%)  1
Pain in extremity  1  2/21 (9.52%)  4 0/21 (0.00%)  0
Nervous system disorders     
Depressed level of consciousness  1  0/21 (0.00%)  0 1/21 (4.76%)  1
Dizziness  1  4/21 (19.05%)  4 2/21 (9.52%)  2
Dysgeusia  1  0/21 (0.00%)  0 1/21 (4.76%)  1
Headache  1  3/21 (14.29%)  3 4/21 (19.05%)  7
Nervous system disorders - Other, idiopathic transient brain brainstem dysfuncti  1  1/21 (4.76%)  1 0/21 (0.00%)  0
Nervous system disorders - Other, imbalance  1  2/21 (9.52%)  2 0/21 (0.00%)  0
Nervous system disorders - Other, numbness  1  3/21 (14.29%)  3 0/21 (0.00%)  0
Nervous system disorders - Other, transient lack of focus  1  1/21 (4.76%)  1 0/21 (0.00%)  0
Paresthesia  1  1/21 (4.76%)  1 1/21 (4.76%)  2
Presyncope  1  2/21 (9.52%)  2 0/21 (0.00%)  0
Spasticity  1  1/21 (4.76%)  1 1/21 (4.76%)  1
Dysesthesia  1  1/21 (4.76%)  1 0/21 (0.00%)  0
Psychiatric disorders     
Anxiety  1  1/21 (4.76%)  1 0/21 (0.00%)  0
Insomnia  1  1/21 (4.76%)  1 2/21 (9.52%)  2
Renal and urinary disorders     
Renal and urinary disorders - Other, bladder pain  1  0/21 (0.00%)  0 1/21 (4.76%)  1
Urinary incontinence  1  1/21 (4.76%)  1 0/21 (0.00%)  0
Reproductive system and breast disorders     
Reproductive system and breast disorders - Other, endometriosis  1  0/21 (0.00%)  0 1/21 (4.76%)  1
Reproductive system and breast disorders - Other, ovarian cyst  1  0/21 (0.00%)  0 1/21 (4.76%)  1
Reproductive system and breast disorders - Other, uterine fibroid  1  0/21 (0.00%)  0 1/21 (4.76%)  1
Respiratory, thoracic and mediastinal disorders     
Allergic rhinitis  1  4/21 (19.05%)  5 1/21 (4.76%)  1
Cough  1  2/21 (9.52%)  2 0/21 (0.00%)  0
Respiratory, thoracic and mediastinal disorders - Other, pneumonia  1  0/21 (0.00%)  0 1/21 (4.76%)  1
Sore throat  1  1/21 (4.76%)  1 0/21 (0.00%)  0
Skin and subcutaneous tissue disorders     
Skin and subcutaneous tissue disorders - Other, bumps on face  1  1/21 (4.76%)  1 0/21 (0.00%)  0
Skin and subcutaneous tissue disorders - Other, hair thinning  1  1/21 (4.76%)  1 1/21 (4.76%)  1
Skin and subcutaneous tissue disorders - Other, rash  1  1/21 (4.76%)  1 0/21 (0.00%)  0
Skin hyperpigmentation  1  0/21 (0.00%)  0 1/21 (4.76%)  1
Urticaria  1  1/21 (4.76%)  1 0/21 (0.00%)  0
Surgical and medical procedures     
Surgical and medical procedures - Other, cataract surgery  1  1/21 (4.76%)  1 0/21 (0.00%)  0
Surgical and medical procedures - Other, gum surgery  1  1/21 (4.76%)  2 0/21 (0.00%)  0
Surgical and medical procedures - Other, laser eye surgery  1  1/21 (4.76%)  1 0/21 (0.00%)  0
Surgical and medical procedures - Other, mole removal  1  1/21 (4.76%)  2 0/21 (0.00%)  0
Surgical and medical procedures - Other, molluscum removal  1  0/21 (0.00%)  0 1/21 (4.76%)  1
Surgical and medical procedures - Other, root canal  1  0/21 (0.00%)  0 1/21 (4.76%)  1
Surgical and medical procedures - Other, tooth extraction  1  0/21 (0.00%)  0 1/21 (4.76%)  1
Surgical and medical procedures - Other, tubal ligation  1  0/21 (0.00%)  0 1/21 (4.76%)  1
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Charles Thornton, MD
Organization: University of Rochester
Phone: 585-275-2542
Responsible Party: Chad Heatwole, University of Rochester
ClinicalTrials.gov Identifier: NCT01406873     History of Changes
Other Study ID Numbers: 3716
Funding Source: FDA/OOPD ( Other Grant/Funding Number: R01FD003716 )
First Submitted: July 20, 2011
First Posted: August 1, 2011
Results First Submitted: March 1, 2018
Results First Posted: March 29, 2018
Last Update Posted: June 19, 2018