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Clinical Trial Nuedexta in Subjects With ALS

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ClinicalTrials.gov Identifier: NCT01806857
Recruitment Status : Completed
First Posted : March 7, 2013
Results First Posted : March 24, 2017
Last Update Posted : March 24, 2017
Sponsor:
Collaborators:
ALS Association
State University of New York - Upstate Medical University
Information provided by (Responsible Party):
Richard A. Smith, MD, Center for Neurologic Study, La Jolla, California,

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Amyotrophic Lateral Sclerosis (ALS)
Interventions Drug: Nuedexta
Drug: Matching Placebo
Enrollment 90
Recruitment Details  
Pre-assignment Details 90 subjects were consented for this trial, however, of the 90 that consented, 30 subjects were found to not meet eligibility criteria, and therefore were not treated.
Arm/Group Title Nuedexta Then Matching Placebo Matching Placebo Then Nuedexta
Hide Arm/Group Description

Subjects in this arm will receive treatment with Nuedexta first for 28 days (±3 days) and then crossed over to receive treatment with matching placebo for 28 days (±3 days).

Nuedexta: Nuedexta PO (by mouth) for 28 ± 3 days

Matching Placebo: matching placebo PO (by mouth) for 28 ± 3 days

Subjects in this arm will receive treatment with matching placebo first for 28 days (±3 days) and then crossed over to receive treatment with Nuedexta for 28 days (±3 days).

Nuedexta: Nuedexta PO (by mouth) for 28 ± 3 days

Matching Placebo: matching placebo PO (by mouth) for 28 ± 3 days

Period Title: Overall Study
Started 31 29
Completed 30 29
Not Completed 1 0
Arm/Group Title All Study Participants
Hide Arm/Group Description [Not Specified]
Overall Number of Baseline Participants 60
Hide Baseline Analysis Population Description
All patients who signed a consent form and had a baseline visit.
Age, Continuous  
Mean (Inter-Quartile Range)
Unit of measure:  Years
Number Analyzed 60 participants
58
(26 to 78)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 60 participants
Female
26
  43.3%
Male
34
  56.7%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 60 participants
Hispanic or Latino 0
Asian 1
Black/African American 2
Caucasian/White 57
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 60 participants
60
Baseline CNS-BFS Total Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 60 participants
58.15  (13.37)
[1]
Measure Description: The Center for Neurologic Study-Bulbar Function Scale (CNS-BFS) is a 21-item self report scale that assesses three domains of bulbar function: speech, swallowing and salivation (sialorrhea). Scores for each question range from 1 (does not apply) to 5 (applies most of the time). The higher the score, the worse the speech, swallowing and salivation (sialorrhea). [Range of score: 21-105]
Baseline ALSFRS-R Total Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 60 participants
34.58  (6.95)
[1]
Measure Description: The ALSFRS-R is a quickly administered (5 min) ordinal rating scale used to determine a subject's assessment of their capability and independence in 12 functional activities. There are 12 questions, graded by the subject 0-4 (4 is normal). Score of 0 (worst) to 48 (best). Reflects speech and swallowing, fine motor skills, large motor skills, and breathing.
Baseline CNS Lability Scale Total Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 60 participants
13.67  (5.55)
[1]
Measure Description: The Center for Neurologic Study-Lability Scale (CNS-LS) is a 7-item self report scale that assesses pseudobulbar affect (PBA) by measuring the perceived frequency of PBA episodes (laughing or crying). Each item is scored using a 5-point Likert scale, from 1 (applies never) to 5 (applies most of the time). Scores range from 5-35.
1.Primary Outcome
Title Bulbar Function Scale (CNS-BFS) Total Score
Hide Description

The Center for Neurologic Study-Bulbar Function Scale (CNS-BFS) is a 21-item self report scale that assesses three domains of bulbar function: speech, swallowing and salivation. Scores for each question range from 1 (does not apply) to 5 (applies most of the time). The higher the score, the worse the speech, swallowing and salivation (sialorrhea). [Range of score: 21-105]

The scale was modeled on the Center for Neurologic Study Emotional Lability Scale (CNS-LS) that has been a robust endpoint in four clinical trials. The scale was validated in a large population of ALS patients (n=122) and detects impaired bulbar function at a sensitivity of 90% and a specificity of 0.97%. Test re-test correlation was 0.92% at six-months (n=53).

Time Frame Average between Screening Visit to Visit 3
Hide Outcome Measure Data
Hide Analysis Population Description
Includes all participants that received at least one dose of intervention.
Arm/Group Title Active Drug (Neudexta) Matching Placebo
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 58 57
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
53.45  (1.07) 59.31  (1.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Active Drug (Neudexta), Matching Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0003
Comments [Not Specified]
Method Random Effects Model
Comments [Not Specified]
2.Primary Outcome
Title Bulbar Function Scale (CNS-BFS) Sialorrhea Score
Hide Description The Center for Neurologic Study-Bulbar Function Scale (CNS-BFS) is a 21-item self report scale that assesses three domains of bulbar function: speech, swallowing and salivation. Scores for each question range from 1 (does not apply) to 5 (applies most of the time). The higher the score, the worse the salivation (sialorrhea). There are 7 salivation (sialorrhea) questions, with a score range of 7 to 35.
Time Frame Average between Screening Visit to Visit 3
Hide Outcome Measure Data
Hide Analysis Population Description
Includes all participants that received at least one dose of intervention.
Arm/Group Title Active Drug (Neudexta) Matching Placebo
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 58 57
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
14.28  (0.37) 15.81  (0.38)
3.Primary Outcome
Title Bulbar Function Scale (CNS-BFS) Speech Score
Hide Description The Center for Neurologic Study-Bulbar Function Scale (CNS-BFS) is a 21-item self report scale that assesses three domains of bulbar function: speech, swallowing and salivation. Scores for each question range from 1 (does not apply) to 5 (applies most of the time). The higher the score, the worse the speech. There are 7 speech questions, with a score range of 7 to 35.
Time Frame Average between Screening Visit to Visit 3
Hide Outcome Measure Data
Hide Analysis Population Description
Includes all participants that received at least one dose of intervention.
Arm/Group Title Active Drug (Neudexta) Matching Placebo
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 58 57
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
22.22  (0.56) 24.57  (0.57)
4.Primary Outcome
Title Bulbar Function Scale (CNS-BFS) Swallowing Score
Hide Description The Center for Neurologic Study-Bulbar Function Scale (CNS-BFS) is a 21-item self report scale that assesses three domains of bulbar function: speech, swallowing and salivation. Scores for each question range from 1 (does not apply) to 5 (applies most of the time). The higher the score, the worse the swallowing. There are 7 swallowing questions, with a score range of 7 to 35.
Time Frame Average between Screening Visit to Visit 3
Hide Outcome Measure Data
Hide Analysis Population Description
Includes all participants that received at least one dose of intervention.
Arm/Group Title Active Drug (Neudexta) Matching Placebo
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 58 57
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
17.14  (0.46) 18.92  (0.47)
5.Secondary Outcome
Title Center for Neurologic Study - Lability Scale (CNS-LS) Total Score
Hide Description The Center for Neurologic Study-Lability Scale (CNS-LS) is a 7-item self report scale that assesses pseudobulbar affect (PBA) by measuring the perceived frequency of PBA episodes (laughing or crying). Each item is scored using a 5-point Likert scale, from 1 (applies never) to 5 (applies most of the time). Scores range from 5-35. The higher the score, the worse the PBA.
Time Frame Average between Screening Visit to Visit 3
Hide Outcome Measure Data
Hide Analysis Population Description
Includes all participants that received at least one dose of intervention.
Arm/Group Title Active Drug (Nuedexta) Matching Placebo
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 58 57
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
10.79  (0.47) 13.72  (0.49)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Active Drug (Nuedexta), Matching Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method Random Effects Model
Comments [Not Specified]
6.Secondary Outcome
Title ALS Functional Rating Scale- Revised (ALSFRS-R) Total Score
Hide Description The ALSFRS-R is a quickly administered (5 min) ordinal rating scale used to determine a subject's assessment of their capability and independence in 12 functional activities. There are 12 questions, graded by the subject 0-4 (4 is normal). Score of 0 (worst) to 48 (best). Reflects speech and swallowing, fine motor skills, large motor skills, and breathing.
Time Frame Average between Screening Visit to Visit 3
Hide Outcome Measure Data
Hide Analysis Population Description
Includes all participants that received at least one dose of intervention.
Arm/Group Title Active Drug (Nuedexta) Matching Placebo
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 58 57
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
34.15  (0.33) 33.7  (0.33)
7.Secondary Outcome
Title Visual Analog Scale - Speech Scores
Hide Description Visual analog scales are useful for measuring complex clinical events and offer the advantage of self-administration and responsiveness to change over time. The scales designed for this study inventory three domains of bulbar function: speech, swallowing and salivation (sialorrhea). For each of these, subjects score themselves by indicating their level of function on a scale of 1 (severe impairment) to 10 (normal). Scores range from 1 to 10; the higher the score, the more normal the function.
Time Frame Average between Baseline Visit to Visit 3
Hide Outcome Measure Data
Hide Analysis Population Description
Includes all participants that received at least one dose of intervention.
Arm/Group Title Active Drug (Nuedexta) Matching Placebo
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 58 57
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
4.97  (0.21) 4.11  (0.21)
8.Secondary Outcome
Title Ashworth Spasticity Scale Score - Right Arm
Hide Description This is a standard measure for spasticity that has been used in numerous ALS clinical trials to assess spasticity due to upper motor neuron dysfunction in ALS. Data is generated from the clinical exam and scored from 1-5, the lowest score indicating normal tone and the highest muscle rigidity.
Time Frame Average between Baseline Visit to Visit 3
Hide Outcome Measure Data
Hide Analysis Population Description
Includes all participants that received at least one dose of intervention.
Arm/Group Title Active Drug (Nuedexta) Matching Placebo
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 58 57
Least Squares Mean (Standard Deviation)
Unit of Measure: units on a scale
1.65  (0.06) 1.53  (0.06)
9.Secondary Outcome
Title Timed Reading of Test Paragraph Result
Hide Description Subjects will be asked to read 'The Rainbow Passage' a commonly used test paragraph utilized by speech pathologists to assess speech rate (words/minute). Study staff will time the subject to determine how many words the subject reads per minute. It is used primarily because it contains every sound in the English language. Subjects will also be observed for loudness, nasality, and intelligibility.
Time Frame Average between Baseline Visit to Visit 3
Hide Outcome Measure Data
Hide Analysis Population Description
Includes all participants that received at least one dose of intervention.
Arm/Group Title Active Drug (Nuedexta) Matching Placebo
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 58 57
Least Squares Mean (Standard Error)
Unit of Measure: words per minute
107.12  (1.79) 103.37  (1.83)
10.Secondary Outcome
Title Average Water Swallowing Test (WST)
Hide Description The Water Swallowing Test (WST) estimates swallowing speed, a useful and reproducible measure. While sitting, subjects are asked to drink 30 milliliters (mL) of liquid. The time for subjects to complete this task is a sensitive measure for the detection of swallowing dysfunction and is a simple measure for serial assessment of subjects. The test will be completed three times, with the best two scores recorded to obtain an average score. Following completion of the WST, the subject's swallowing abilities (choking, spillage, and effort) will be observed.
Time Frame Average between Baseline Visit to Visit 3
Hide Outcome Measure Data
Hide Analysis Population Description
Includes all participants that received at least one dose of intervention.
Arm/Group Title Active Drug (Nuedexta) Matching Placebo
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 58 57
Least Squares Mean (Standard Error)
Unit of Measure: seconds
12.16  (0.71) 13.11  (0.72)
11.Secondary Outcome
Title Visual Analog Scale - Swallowing Score
Hide Description Visual analog scales are useful for measuring complex clinical events and offer the advantage of self-administration and responsiveness to change over time. The scales designed for this study inventory three domains of bulbar function: speech, swallowing and salivation (sialorrhea). For each of these, subjects score themselves by indicating their level of function on a scale of 1 (severe impairment) to 10 (normal). Scores range from 1 to 10; the higher the score, the more normal the function.
Time Frame Average between Baseline Visit to Visit 3
Hide Outcome Measure Data
Hide Analysis Population Description
Includes all participants that received at least one dose of intervention.
Arm/Group Title Active Drug (Nuedexta) Matching Placebo
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 58 57
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
7.23  (0.29) 6.93  (0.3)
12.Secondary Outcome
Title Visual Analog Scale - Salivation (Sialorrhea) Score
Hide Description Visual analog scales are useful for measuring complex clinical events and offer the advantage of self-administration and responsiveness to change over time. The scales designed for this study inventory three domains of bulbar function: speech, swallowing and salivation (sialorrhea). For each of these, subjects score themselves by indicating their level of function on a scale of 1 (severe impairment) to 10 (normal). Scores range from 1 to 10; the higher the score, the more normal the function.
Time Frame Average between Baseline Visit to Visit 3
Hide Outcome Measure Data
Hide Analysis Population Description
Includes all participants that received at least one dose of intervention.
Arm/Group Title Active Drug (Nuedexta) Matching Placebo
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 58 57
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
6.78  (0.31) 6.78  (0.32)
13.Secondary Outcome
Title Average Solids Swallowing Test
Hide Description The Time Swallowing Test assesses the subject's ability to swallow solids. For this test, the subject will be asked to consume a tablespoon of cereal containing 5 cheerios. The subject will be instructed to close their mouth, chew and subsequently swallow the bolus. The time to complete this task will be recorded. The test will be completed three times to obtain an average score.
Time Frame Average between Baseline Visit to Visit 3
Hide Outcome Measure Data
Hide Analysis Population Description
Includes all participants that received at least one dose of intervention.
Arm/Group Title Active Drug (Nuedexta) Matching Placebo
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 58 57
Least Squares Mean (Standard Error)
Unit of Measure: seconds
18.53  (1.16) 19.45  (1.19)
14.Secondary Outcome
Title Ashworth Spasticity Scale Score - Left Arm
Hide Description This is a standard measure for spasticity that has been used in numerous ALS clinical trials to assess spasticity due to upper motor neuron dysfunction in ALS. Data is generated from the clinical exam and scored from 1-5, the lowest score indicating normal tone and the highest muscle rigidity.
Time Frame Average between Baseline Visit to Visit 3
Hide Outcome Measure Data
Hide Analysis Population Description
Includes all participants that received at least one dose of intervention.
Arm/Group Title Active Drug (Nuedexta) Matching Placebo
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 58 57
Least Squares Mean (Standard Deviation)
Unit of Measure: units on a scale
1.62  (0.06) 1.67  (0.07)
15.Secondary Outcome
Title Ashworth Spasticity Scale Score - Right Leg
Hide Description This is a standard measure for spasticity that has been used in numerous ALS clinical trials to assess spasticity due to upper motor neuron dysfunction in ALS. Data is generated from the clinical exam and scored from 1-5, the lowest score indicating normal tone and the highest muscle rigidity.
Time Frame Average between Baseline Visit to Visit 3
Hide Outcome Measure Data
Hide Analysis Population Description
Includes all participants that received at least one dose of intervention.
Arm/Group Title Active Drug (Nuedexta) Matching Placebo
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 58 57
Least Squares Mean (Standard Deviation)
Unit of Measure: units on a scale
1.94  (0.1) 1.82  (0.1)
16.Secondary Outcome
Title Ashworth Spasticity Scale Score - Left Leg
Hide Description This is a standard measure for spasticity that has been used in numerous ALS clinical trials to assess spasticity due to upper motor neuron dysfunction in ALS. Data is generated from the clinical exam and scored from 1-5, the lowest score indicating normal tone and the highest muscle rigidity.
Time Frame Average between Baseline Visit to Visit 3
Hide Outcome Measure Data
Hide Analysis Population Description
Includes all participants that received at least one dose of intervention.
Arm/Group Title Active Drug (Nuedexta) Matching Placebo
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 58 57
Least Squares Mean (Standard Deviation)
Unit of Measure: units on a scale
1.91  (0.09) 1.91  (0.09)
Time Frame 28 days +/- 3 days for each Intervention.
Adverse Event Reporting Description Safety population included all participants who received at least one dose of intervention.
 
Arm/Group Title Active Drug (Neudexta) Matching Placebo
Hide Arm/Group Description Includes all subjects that took the active drug (Neudexta) Includes all subjects that took matching placebo
All-Cause Mortality
Active Drug (Neudexta) Matching Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Active Drug (Neudexta) Matching Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/58 (1.72%)      0/57 (0.00%)    
Respiratory, thoracic and mediastinal disorders     
Respiratory Failure *  1/58 (1.72%)  1 0/57 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Active Drug (Neudexta) Matching Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   21/58 (36.21%)      4/57 (7.02%)    
Gastrointestinal disorders     
Constipation *  5/58 (8.62%)  5 2/57 (3.51%)  2
Diarrhoea *  5/58 (8.62%)  5 1/57 (1.75%)  1
Nausea *  4/58 (6.90%)  5 0/57 (0.00%)  0
Nervous system disorders     
Dizziness *  7/58 (12.07%)  10 1/57 (1.75%)  1
*
Indicates events were collected by non-systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Richard Smith, MD
Organization: Center for Neurological Study
Phone: 858-455-5463
Responsible Party: Richard A. Smith, MD, Center for Neurologic Study, La Jolla, California,
ClinicalTrials.gov Identifier: NCT01806857     History of Changes
Other Study ID Numbers: 2012P001274
3FKVAD ( Other Grant/Funding Number: ALSA )
First Submitted: March 5, 2013
First Posted: March 7, 2013
Results First Submitted: August 9, 2016
Results First Posted: March 24, 2017
Last Update Posted: March 24, 2017