Trial Outcomes & Findings for Clinical Trial Nuedexta in Subjects With ALS (NCT NCT01806857)

NCT ID: NCT01806857

Last Updated: 2017-03-24

Results Overview

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).

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 90 participants
• Primary outcome timeframe: Average between Screening Visit to Visit 3
• Results posted on: 2017-03-24

Participant Flow

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.

Participant milestones

Measure	Nuedexta Then Matching Placebo 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	Matching Placebo Then Nuedexta 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
Overall Study STARTED	31	29
Overall Study COMPLETED	30	29
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Clinical Trial Nuedexta in Subjects With ALS

Baseline characteristics by cohort

Measure	All Study Participants n=60 Participants
Age, Continuous	58 years n=93 Participants
Sex: Female, Male Female	26 Participants n=93 Participants
Sex: Female, Male Male	34 Participants n=93 Participants
Race/Ethnicity, Customized Hispanic or Latino	0 participants n=93 Participants
Race/Ethnicity, Customized Asian	1 participants n=93 Participants
Race/Ethnicity, Customized Black/African American	2 participants n=93 Participants
Race/Ethnicity, Customized Caucasian/White	57 participants n=93 Participants
Region of Enrollment United States	60 participants n=93 Participants
Baseline CNS-BFS Total Score	58.15 units on a scale STANDARD_DEVIATION 13.37 • n=93 Participants
Baseline ALSFRS-R Total Score	34.58 units on a scale STANDARD_DEVIATION 6.95 • n=93 Participants
Baseline CNS Lability Scale Total Score	13.67 units on a scale STANDARD_DEVIATION 5.55 • n=93 Participants

PRIMARY outcome

Timeframe: Average between Screening Visit to Visit 3

Population: Includes all participants that received at least one dose of intervention.

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).

Outcome measures

Measure	Active Drug (Neudexta) n=58 Participants	Matching Placebo n=57 Participants
Bulbar Function Scale (CNS-BFS) Total Score	53.45 units on a scale Standard Error 1.07	59.31 units on a scale Standard Error 1.1

PRIMARY outcome

Timeframe: Average between Screening Visit to Visit 3

Population: Includes all participants that received at least one dose of intervention.

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.

Outcome measures

Measure	Active Drug (Neudexta) n=58 Participants	Matching Placebo n=57 Participants
Bulbar Function Scale (CNS-BFS) Sialorrhea Score	14.28 units on a scale Standard Error 0.37	15.81 units on a scale Standard Error 0.38

PRIMARY outcome

Timeframe: Average between Screening Visit to Visit 3

Population: Includes all participants that received at least one dose of intervention.

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.

Outcome measures

Measure	Active Drug (Neudexta) n=58 Participants	Matching Placebo n=57 Participants
Bulbar Function Scale (CNS-BFS) Speech Score	22.22 units on a scale Standard Error 0.56	24.57 units on a scale Standard Error 0.57

PRIMARY outcome

Timeframe: Average between Screening Visit to Visit 3

Population: Includes all participants that received at least one dose of intervention.

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.

Outcome measures

Measure	Active Drug (Neudexta) n=58 Participants	Matching Placebo n=57 Participants
Bulbar Function Scale (CNS-BFS) Swallowing Score	17.14 units on a scale Standard Error 0.46	18.92 units on a scale Standard Error 0.47

SECONDARY outcome

Timeframe: Average between Screening Visit to Visit 3

Population: Includes all participants that received at least one dose of intervention.

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.

Outcome measures

Measure	Active Drug (Neudexta) n=58 Participants	Matching Placebo n=57 Participants
Center for Neurologic Study - Lability Scale (CNS-LS) Total Score	10.79 units on a scale Standard Error 0.47	13.72 units on a scale Standard Error 0.49

SECONDARY outcome

Timeframe: Average between Screening Visit to Visit 3

Population: Includes all participants that received at least one dose of intervention.

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.

Outcome measures

Measure	Active Drug (Neudexta) n=58 Participants	Matching Placebo n=57 Participants
ALS Functional Rating Scale- Revised (ALSFRS-R) Total Score	34.15 units on a scale Standard Error 0.33	33.7 units on a scale Standard Error 0.33

SECONDARY outcome

Timeframe: Average between Baseline Visit to Visit 3

Population: Includes all participants that received at least one dose of intervention.

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.

Outcome measures

Measure	Active Drug (Neudexta) n=58 Participants	Matching Placebo n=57 Participants
Visual Analog Scale - Speech Scores	4.97 units on a scale Standard Error 0.21	4.11 units on a scale Standard Error 0.21

SECONDARY outcome

Timeframe: Average between Baseline Visit to Visit 3

Population: Includes all participants that received at least one dose of intervention.

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.

Outcome measures

Measure	Active Drug (Neudexta) n=58 Participants	Matching Placebo n=57 Participants
Ashworth Spasticity Scale Score - Right Arm	1.65 units on a scale Standard Deviation 0.06	1.53 units on a scale Standard Deviation 0.06

SECONDARY outcome

Timeframe: Average between Baseline Visit to Visit 3

Population: Includes all participants that received at least one dose of intervention.

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.

Outcome measures

Measure	Active Drug (Neudexta) n=58 Participants	Matching Placebo n=57 Participants
Timed Reading of Test Paragraph Result	107.12 words per minute Standard Error 1.79	103.37 words per minute Standard Error 1.83

SECONDARY outcome

Timeframe: Average between Baseline Visit to Visit 3

Population: Includes all participants that received at least one dose of intervention.

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.

Outcome measures

Measure	Active Drug (Neudexta) n=58 Participants	Matching Placebo n=57 Participants
Average Water Swallowing Test (WST)	12.16 seconds Standard Error 0.71	13.11 seconds Standard Error 0.72

SECONDARY outcome

Timeframe: Average between Baseline Visit to Visit 3

Population: Includes all participants that received at least one dose of intervention.

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.

Outcome measures

Measure	Active Drug (Neudexta) n=58 Participants	Matching Placebo n=57 Participants
Visual Analog Scale - Swallowing Score	7.23 units on a scale Standard Error 0.29	6.93 units on a scale Standard Error 0.3

SECONDARY outcome

Timeframe: Average between Baseline Visit to Visit 3

Population: Includes all participants that received at least one dose of intervention.

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.

Outcome measures

Measure	Active Drug (Neudexta) n=58 Participants	Matching Placebo n=57 Participants
Visual Analog Scale - Salivation (Sialorrhea) Score	6.78 units on a scale Standard Error 0.31	6.78 units on a scale Standard Error 0.32

SECONDARY outcome

Timeframe: Average between Baseline Visit to Visit 3

Population: Includes all participants that received at least one dose of intervention.

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.

Outcome measures

Measure	Active Drug (Neudexta) n=58 Participants	Matching Placebo n=57 Participants
Average Solids Swallowing Test	18.53 seconds Standard Error 1.16	19.45 seconds Standard Error 1.19

SECONDARY outcome

Timeframe: Average between Baseline Visit to Visit 3

Population: Includes all participants that received at least one dose of intervention.

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.

Outcome measures

Measure	Active Drug (Neudexta) n=58 Participants	Matching Placebo n=57 Participants
Ashworth Spasticity Scale Score - Left Arm	1.62 units on a scale Standard Deviation 0.06	1.67 units on a scale Standard Deviation 0.07

SECONDARY outcome

Timeframe: Average between Baseline Visit to Visit 3

Population: Includes all participants that received at least one dose of intervention.

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.

Outcome measures

Measure	Active Drug (Neudexta) n=58 Participants	Matching Placebo n=57 Participants
Ashworth Spasticity Scale Score - Right Leg	1.94 units on a scale Standard Deviation 0.1	1.82 units on a scale Standard Deviation 0.1

SECONDARY outcome

Timeframe: Average between Baseline Visit to Visit 3

Population: Includes all participants that received at least one dose of intervention.

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.

Outcome measures

Measure	Active Drug (Neudexta) n=58 Participants	Matching Placebo n=57 Participants
Ashworth Spasticity Scale Score - Left Leg	1.91 units on a scale Standard Deviation 0.09	1.91 units on a scale Standard Deviation 0.09

Adverse Events

Active Drug (Neudexta)

Serious events: 1 serious events

Other events: 21 other events

Deaths: 0 deaths

Matching Placebo

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Measure	Active Drug (Neudexta) n=58 participants at risk Includes all subjects that took the active drug (Neudexta)	Matching Placebo n=57 participants at risk Includes all subjects that took matching placebo
Respiratory, thoracic and mediastinal disorders Respiratory Failure	1.7% 1/58 • Number of events 1 • 28 days +/- 3 days for each Intervention. Safety population included all participants who received at least one dose of intervention.	0.00% 0/57 • 28 days +/- 3 days for each Intervention. Safety population included all participants who received at least one dose of intervention.

Other adverse events

Measure	Active Drug (Neudexta) n=58 participants at risk Includes all subjects that took the active drug (Neudexta)	Matching Placebo n=57 participants at risk Includes all subjects that took matching placebo
Gastrointestinal disorders Constipation	8.6% 5/58 • Number of events 5 • 28 days +/- 3 days for each Intervention. Safety population included all participants who received at least one dose of intervention.	3.5% 2/57 • Number of events 2 • 28 days +/- 3 days for each Intervention. Safety population included all participants who received at least one dose of intervention.
Gastrointestinal disorders Diarrhoea	8.6% 5/58 • Number of events 5 • 28 days +/- 3 days for each Intervention. Safety population included all participants who received at least one dose of intervention.	1.8% 1/57 • Number of events 1 • 28 days +/- 3 days for each Intervention. Safety population included all participants who received at least one dose of intervention.
Gastrointestinal disorders Nausea	6.9% 4/58 • Number of events 5 • 28 days +/- 3 days for each Intervention. Safety population included all participants who received at least one dose of intervention.	0.00% 0/57 • 28 days +/- 3 days for each Intervention. Safety population included all participants who received at least one dose of intervention.
Nervous system disorders Dizziness	12.1% 7/58 • Number of events 10 • 28 days +/- 3 days for each Intervention. Safety population included all participants who received at least one dose of intervention.	1.8% 1/57 • Number of events 1 • 28 days +/- 3 days for each Intervention. Safety population included all participants who received at least one dose of intervention.

Additional Information

Richard Smith, MD

Center for Neurological Study

Phone: 858-455-5463

Email: cnsonline@ymail.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place