Amyotrophic Lateral Sclerosis
Conditions
Keywords
ALS, Amyotrophic Lateral Sclerosis, Lou Gehrig, Lou Gehrig's, Lou Gehrig's disease, Motor Neuron Disease, Nervous System Diseases, KNS-760704, BIIB050
Brief summary
This was a 2-part study of dexpramipexole in patients with ALS. Part 1 was a randomized, placebo-controlled, multi-center study to evaluate the safety, tolerability, and clinical effects of oral administration of 3 dosage levels of dexpramipexole vs. placebo for 12 weeks. Part 2 was a randomized, double-blind, 2-arm, parallel group, extension study evaluating the safety, tolerability, and clinical effects of oral administration of 2 dosage levels of dexpramipexole for up to 72 weeks.
Detailed description
This study was a two-part, multicenter, double-blind study in subjects with ALS to evaluate the safety and tolerability of dexpramipexole treatment, as well as the preliminary effects on measures of clinical function and mortality of dexpramipexole treatment. In part 1, 102 subjects with ALS were randomized at 20 US sites to receive placebo, dexpramipexole at 50 mg/day; dexpramipexole at 150 mg/day; or dexpramipexole at 300 mg/day for 12 weeks. Participants who completed Part 1 were eligible to enroll into Part 2. Part 2 was a randomized, double-blind, 2-arm, parallel-group, extension study evaluating the longer-term safety, tolerability, and clinical effects of oral administration of 2 dosage levels of dexpramipexole. In part 2, following a 4-week, placebo washout, continuing subjects received dexpramipexole at 50 mg/day or 300 mg/day as double-blind treatment for up to 72 additional weeks (Part 2 duration was up to a total of 76 weeks, including the 4 week placebo portion).
Interventions
DRUGPlacebo
Placebo: 2 tablets taken orally twice daily
DRUGDexpramipexole 50 mg/day
Dexpramipexole: 2 x 12.5 mg tablets taken orally twice daily
DRUGDexpramipexole 150 mg/day
Dexpramipexole: 2 x 37.5 mg tablets taken orally twice daily
DRUGDexpramipexole 300 mg/day
Dexpramipexole: 2 x 75 mg tablets taken orally twice daily
Sponsors
Knopp Biosciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Matching placebo during Part 1 and Part 2 placebo washout.
Eligibility
Sex/Gender
ALL
Age
21 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Patients with diagnosis of familial or sporadic ALS, defined as meeting the possible, laboratory-supported probable, probable, or definite criteria for a diagnosis of ALS according to the World Federation of Neurology El Escorial criteria * Patients with ALS symptom onset \< 24 months from randomization * Patients with upright vital capacity (VC) \> 65% of predicted for age, height, and gender
Exclusion criteria
* Patients in whom causes of neuromuscular weakness other than ALS have not been excluded * Patients without clinical evidence of upper motor neuron dysfunction * Patients with clinically suspected ALS according to the World Federation of Neurology El Escorial criteria * Patients with prior exposure to KNS-760704 or the R(+) enantiomer of pramipexole (i.e., R(+)-pramipexole) * Patients taking other investigational agents (including lithium) within 30 days of randomization or during the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Number of Participants With Potentially Clinically Significant Hematology Results by Treatment Group | 12 weeks | Number of Participants with Potentially Clinically Significant Hematology Results by Treatment Group. Percentages based on number of patients with at least one non-missing post-baseline value in each treatment group. Patients are only counted once per criterion per laboratory test. |
| Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | 12 weeks | Number of Participants with Potentially Clinically Significant Blood Chemistry Results by Treatment Group. Percentages based on number of patients with at least one non-missing post-baseline value in each treatment group. Patients are only counted once per criterion per laboratory test. |
| Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | 12 weeks | Number of Participants with Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group. Percentages are based on the number of patients with at least one non-missing post-baseline value in each treatment group. |
| Part 1: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group | 12 weeks | Number of Participants with Potentially Clinically Significant Vital Sign Measurements by Treatment Group. Percentages are based on the number of patients with at least one non-missing post-baseline value in each treatment group. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 2 Placebo Washout: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings | 4 weeks | Number of Participants with Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group. Percentages are based on the number of patients with at least one non-missing post-baseline value in each treatment group. |
| Part 2 Placebo Washout: Number of Participants With Potentially Clinically Significant Vital Sign Measurements | 4 weeks | Number of Participants with Potentially Clinically Significant Vital Sign Measurements by Treatment Group. Percentages are based on the number of patients with at least one non-missing post-baseline value in each treatment group. |
| Part 2 Placebo Washout: Absolute Change in ALSFRS-R Total Score | 4 weeks | The ALSFRS-R (ALS functional rating scale with respiratory component) is a validated scale which measures 4 functional domains, comprising respiratory function, bulbar function, gross motor skills, and fine motor skills. There are a total of 12 questions, each scored from 0 to 4 for a total possible score of 48, with higher scores representing better function. Units are points on the ALSFRS-R score as an absolute change from the baseline of the placebo washout to week 4 of the placebo washout. |
| Part 2 Placebo Washout: Absolute Change in Upright Vital Capacity (Percent Predicted) From Baseline to End of Placebo Washout (Week 4) | 4 weeks | Absolute change in Upright Vital Capacity From Baseline to Week 4. Units are percent of predicted Upright Vital Capacity. A negative change indicates clinical worsening. |
| Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Hematology Results by Treatment Group | up to 76 weeks | Number of Participants with Potentially Clinically Significant Hematology Results by Treatment Group. Percentages based on number of patients with at least one non-missing post-baseline value in each treatment group. Patients are only counted once per criterion per parameter. |
| Part 1: Slope of ALSFRS-R (ALS Functional Rating Scale With Respiratory Component) From Baseline to Week 12 by Treatment Group | 12 weeks | The ALSFRS-R (ALS functional rating scale with respiratory component) is a validated scale which measures 4 functional domains, comprising respiratory function, bulbar function, gross motor skills, and fine motor skills. There are a total of 12 questions, each scored from 0 to 4 for a total possible score of 48, with higher scores representing better function. Slope is calculated using a linear mixed effects model with x-axis time in months and y-axis ALSFRS-R score. Units for slope are change per month in units on the ALSFRS-R scale. |
| Part 2 Double-Blind Treatment: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | up to 76 weeks | Number of Participants with Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group. Percentages based on number of patients with at least one non-missing post-baseline value in each treatment group. Patients are only counted once per criterion per parameter. |
| Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group | up to 76 weeks | Number of Participants with Potentially Clinically Significant Vital Sign Measurements by Treatment Group. Percentages based on number of patients with at least one non-missing post-baseline value in each treatment group. Patients are only counted once per criterion per parameter. |
| Part 2 Double-Blind Treatment: Slope of the ALSFRS-R (ALS Functional Rating Scale With Respiratory Component) From Baseline to Week 28 by Treatment Group | 28 weeks | The ALSFRS-R (ALS functional rating scale with respiratory component) is a validated scale which measures 4 functional domains, comprising respiratory function, bulbar function, gross motor skills, and fine motor skills. There are a total of 12 questions, each scored from 0 to 4 for a total possible score of 48, with higher scores representing better function. Slope is calculated using a linear mixed effects model with x-axis time in months and y-axis ALSFRS-R score. Units for slope are change per month n units on the ALSFRS-R scale. |
| Part 2 Double-Blind Treatment: Slope of Percent Predicted Upright Vital Capacity From Baseline by Treatment Group | Baseline of randomized phase of Part 2 to week 28 of randomized phase of Part 2 | Slope of Upright Vital Capacity (percent predicted) through Week 28. A negative change indicates clinical worsening. Slope is calculated using a linear mixed effects model with x-axis time in months and y-axis percent predicted upright vital capacity. Units for slope are change per month in percent predicted upright vital capacity. |
| Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | up to 76 weeks | Number of Participants with Potentially Clinically Significant Blood Chemistry Results by Treatment Group. Percentages based on number of patients with at least one non-missing post-baseline value in each treatment group. Patients are only counted once per criterion per parameter. |
| Part 1: Slope of Upright Vital Capacity From Baseline to Week 12 by Treatment Group | 12 weeks | Slope of change in Upright Vital Capacity (percent predicted upright vital capacity) from Baseline to Week 12. A negative change/slope indicates clinical worsening. Slope is calculated using a linear mixed effects model with x-axis time in months and y-axis as percent predicted upright vital capacity. Units for slope are change per month in percent predicted upright vital capacity. |
| Part 2 Placebo Washout: Number of Participants With Potentially Clinically Significant Hematology | 4 weeks | Number of Participants with Potentially Clinically Significant Hematology Results by Treatment Group. Percentages based on number of patients with at least one non-missing post-baseline value in each treatment group. Patients are only counted once per criterion per laboratory test. |
| Part 2 Placebo Washout: Number of Participants With Potentially Clinically Significant Blood Chemistry Results | 4 weeks | Number of Participants with Potentially Clinically Significant Blood Chemistry Results by Treatment Group. Percentages based on number of patients with at least one non-missing post-baseline value in each treatment group. Patients are only counted once per criterion per laboratory test. |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited for the study across 20 recruiting centers US between 09 April 2008 and 26 January 2009 in medical centers located the USA.
Pre-assignment details
Study conducted in 2 parts: When the first 12 weeks (Part 1) was completed, eligible continuing subjects entered a 4 week placebo washout before being re-randomized to receive either 50 mg/day dexpramipexole or 300 mg/day dexpramipexole for up to 72 additional weeks.
Participants by arm
| Arm | Count |
|---|---|
| Placebo PBO BID for 12 weeks | 27 |
| 50 mg/Day 25 mg BID for 12 weeks | 23 |
| 150 mg/Day 75 mg BID for 12 weeks | 26 |
| 300 mg/Day 150 mg BID for 12 weeks | 26 |
| Total | 102 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Part 1: 12-week Double-Blind Treatment | Adverse Event | 1 | 0 | 0 | 1 |
| Part 1: 12-week Double-Blind Treatment | Physician Decision | 0 | 1 | 0 | 0 |
| Part 1: 12-week Double-Blind Treatment | Withdrawal by Subject | 0 | 0 | 0 | 1 |
| Part 2: 4-week Placebo Washout | Death | 3 | 0 | 0 | 0 |
| Part 2: 4-week Placebo Washout | Lost to Follow-up | 1 | 0 | 0 | 0 |
| Part 2: 4-week Placebo Washout | Withdrawal by Subject | 1 | 0 | 0 | 0 |
| Part 2: 76-week Double-Blind Treatment | Adverse Event | 0 | 1 | 0 | 4 |
| Part 2: 76-week Double-Blind Treatment | Death | 0 | 7 | 0 | 5 |
| Part 2: 76-week Double-Blind Treatment | Inability to attend study visits in person | 0 | 1 | 0 | 1 |
| Part 2: 76-week Double-Blind Treatment | Lost to Follow-up | 0 | 1 | 0 | 0 |
| Part 2: 76-week Double-Blind Treatment | Withdrawal by Subject | 0 | 5 | 0 | 4 |
Baseline characteristics
| Characteristic | Placebo | 50 mg/Day | 150 mg/Day | 300 mg/Day | Total |
|---|---|---|---|---|---|
| Age, Continuous | 55.8 years STANDARD_DEVIATION 9.07 | 58.1 years STANDARD_DEVIATION 10.2 | 56.01 years STANDARD_DEVIATION 11.03 | 58.2 years STANDARD_DEVIATION 10.96 | 57.0 years STANDARD_DEVIATION 10.25 |
| Age, Customized 50 to 65 years | 16 Participants | 10 Participants | 17 Participants | 11 Participants | 54 Participants |
| Age, Customized < 50 years | 7 Participants | 6 Participants | 6 Participants | 8 Participants | 27 Participants |
| Age, Customized > 65 years | 4 Participants | 7 Participants | 3 Participants | 7 Participants | 21 Participants |
| Body mass index | 25.66 kg/m^2 STANDARD_DEVIATION 3.934 | 26.86 kg/m^2 STANDARD_DEVIATION 6.369 | 25.78 kg/m^2 STANDARD_DEVIATION 4.492 | 26.81 kg/m^2 STANDARD_DEVIATION 4.189 | 26.27 kg/m^2 STANDARD_DEVIATION 4.752 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 4 Participants | 2 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants | 22 Participants | 21 Participants | 24 Participants | 91 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 1 Participants | 1 Participants | 0 Participants | 4 Participants |
| Height | 170.28 cm STANDARD_DEVIATION 10.349 | 170.34 cm STANDARD_DEVIATION 8.209 | 172.22 cm STANDARD_DEVIATION 12.591 | 174.98 cm STANDARD_DEVIATION 9.932 | 171.99 cm STANDARD_DEVIATION 10.471 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 0 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 25 Participants | 21 Participants | 25 Participants | 24 Participants | 95 Participants |
| Sex: Female, Male Female | 14 Participants | 14 Participants | 18 Participants | 19 Participants | 65 Participants |
| Sex: Female, Male Male | 13 Participants | 9 Participants | 8 Participants | 7 Participants | 37 Participants |
| Weight | 74.7 kg STANDARD_DEVIATION 15.83 | 78.2 kg STANDARD_DEVIATION 19.89 | 77.4 kg STANDARD_DEVIATION 18.73 | 82.1 kg STANDARD_DEVIATION 14.35 | 78.1 kg STANDARD_DEVIATION 17.18 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 27 | 0 / 23 | 0 / 26 | 0 / 26 | 3 / 97 | 15 / 48 | 9 / 44 |
| other Total, other adverse events | 25 / 27 | 19 / 23 | 25 / 26 | 23 / 26 | 46 / 97 | 46 / 48 | 41 / 44 |
| serious Total, serious adverse events | 0 / 27 | 2 / 23 | 0 / 26 | 3 / 26 | 5 / 97 | 14 / 48 | 12 / 44 |
Outcome results
Primary
Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group
Number of Participants with Potentially Clinically Significant Blood Chemistry Results by Treatment Group. Percentages based on number of patients with at least one non-missing post-baseline value in each treatment group. Patients are only counted once per criterion per laboratory test.
Time frame: 12 weeks
Population: Safety Population: Data from all enrolled subjects who were randomized in Part 1 and received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Glucose (mg/dL) Low < 40 mg/dL | 0 Participants |
| Placebo | Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Alkaline Phosphatase (U/L) > 1.5xULN | 0 Participants |
| Placebo | Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | AST (SGOT) (U/L) > 3xULN | 0 Participants |
| Placebo | Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | ALT (SGPT) (U/L) > 3xULN | 0 Participants |
| Placebo | Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Calcium (mg/dL) Low < 7 mg/dL | 0 Participants |
| Placebo | Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | BUN (mg/dL) > 5xULN | 0 Participants |
| Placebo | Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Potassium (mEq/L) High > 6.5 mEq/L | 0 Participants |
| Placebo | Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Calcium (mg/dL) High > 12.5 mg/dL | 0 Participants |
| Placebo | Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Total Bilirubin (mg/dL) > 1.5xULN | 0 Participants |
| Placebo | Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Creatinine (mg/dL) > 3xULN | 0 Participants |
| Placebo | Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Sodium (mEq/L) high > 157 mEq/L | 0 Participants |
| Placebo | Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Creatine Kinase (U/L) >= 10xULN | 0 Participants |
| Placebo | Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Glucose (mg/dL) High > 250 mg/dL | 1 Participants |
| Placebo | Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Sodium (mEq/L) low < 123 mEq/L | 0 Participants |
| Placebo | Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Potassium (mEq/L) Low < 2.5 mEq/L | 0 Participants |
| 50 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Sodium (mEq/L) low < 123 mEq/L | 0 Participants |
| 50 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Sodium (mEq/L) high > 157 mEq/L | 0 Participants |
| 50 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Potassium (mEq/L) High > 6.5 mEq/L | 0 Participants |
| 50 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Potassium (mEq/L) Low < 2.5 mEq/L | 0 Participants |
| 50 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | AST (SGOT) (U/L) > 3xULN | 0 Participants |
| 50 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Calcium (mg/dL) Low < 7 mg/dL | 0 Participants |
| 50 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Creatine Kinase (U/L) >= 10xULN | 0 Participants |
| 50 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Calcium (mg/dL) High > 12.5 mg/dL | 0 Participants |
| 50 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Alkaline Phosphatase (U/L) > 1.5xULN | 0 Participants |
| 50 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | BUN (mg/dL) > 5xULN | 0 Participants |
| 50 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | ALT (SGPT) (U/L) > 3xULN | 0 Participants |
| 50 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Glucose (mg/dL) High > 250 mg/dL | 0 Participants |
| 50 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Creatinine (mg/dL) > 3xULN | 0 Participants |
| 50 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Total Bilirubin (mg/dL) > 1.5xULN | 0 Participants |
| 50 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Glucose (mg/dL) Low < 40 mg/dL | 0 Participants |
| 150 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Sodium (mEq/L) low < 123 mEq/L | 0 Participants |
| 150 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Total Bilirubin (mg/dL) > 1.5xULN | 0 Participants |
| 150 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | ALT (SGPT) (U/L) > 3xULN | 0 Participants |
| 150 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | AST (SGOT) (U/L) > 3xULN | 0 Participants |
| 150 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Creatine Kinase (U/L) >= 10xULN | 0 Participants |
| 150 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Alkaline Phosphatase (U/L) > 1.5xULN | 0 Participants |
| 150 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | BUN (mg/dL) > 5xULN | 0 Participants |
| 150 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Creatinine (mg/dL) > 3xULN | 0 Participants |
| 150 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Sodium (mEq/L) high > 157 mEq/L | 0 Participants |
| 150 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Potassium (mEq/L) Low < 2.5 mEq/L | 0 Participants |
| 150 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Potassium (mEq/L) High > 6.5 mEq/L | 0 Participants |
| 150 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Glucose (mg/dL) Low < 40 mg/dL | 0 Participants |
| 150 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Glucose (mg/dL) High > 250 mg/dL | 0 Participants |
| 150 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Calcium (mg/dL) Low < 7 mg/dL | 0 Participants |
| 150 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Calcium (mg/dL) High > 12.5 mg/dL | 0 Participants |
| 300 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Creatine Kinase (U/L) >= 10xULN | 1 Participants |
| 300 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | ALT (SGPT) (U/L) > 3xULN | 2 Participants |
| 300 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Glucose (mg/dL) Low < 40 mg/dL | 0 Participants |
| 300 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Creatinine (mg/dL) > 3xULN | 0 Participants |
| 300 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | BUN (mg/dL) > 5xULN | 0 Participants |
| 300 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Total Bilirubin (mg/dL) > 1.5xULN | 0 Participants |
| 300 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Glucose (mg/dL) High > 250 mg/dL | 0 Participants |
| 300 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Alkaline Phosphatase (U/L) > 1.5xULN | 1 Participants |
| 300 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | AST (SGOT) (U/L) > 3xULN | 1 Participants |
| 300 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Calcium (mg/dL) High > 12.5 mg/dL | 0 Participants |
| 300 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Potassium (mEq/L) Low < 2.5 mEq/L | 0 Participants |
| 300 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Sodium (mEq/L) high > 157 mEq/L | 0 Participants |
| 300 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Calcium (mg/dL) Low < 7 mg/dL | 0 Participants |
| 300 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Potassium (mEq/L) High > 6.5 mEq/L | 0 Participants |
| 300 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Sodium (mEq/L) low < 123 mEq/L | 0 Participants |
Primary
Part 1: Number of Participants With Potentially Clinically Significant Hematology Results by Treatment Group
Number of Participants with Potentially Clinically Significant Hematology Results by Treatment Group. Percentages based on number of patients with at least one non-missing post-baseline value in each treatment group. Patients are only counted once per criterion per laboratory test.
Time frame: 12 weeks
Population: Safety Population: Data from all enrolled subjects who were randomized in Part 1 and received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Part 1: Number of Participants With Potentially Clinically Significant Hematology Results by Treatment Group | Hemoglobin (g/dL) < 8 g/dL | 0 Participants |
| Placebo | Part 1: Number of Participants With Potentially Clinically Significant Hematology Results by Treatment Group | Neutrophils (x10^3/uL) < 1000/uL | 0 Participants |
| Placebo | Part 1: Number of Participants With Potentially Clinically Significant Hematology Results by Treatment Group | Platelets (x10^3/uL) < 50,000/uL | 0 Participants |
| Placebo | Part 1: Number of Participants With Potentially Clinically Significant Hematology Results by Treatment Group | Eosinophils (x10^3/uL) > 5000/uL | 0 Participants |
| Placebo | Part 1: Number of Participants With Potentially Clinically Significant Hematology Results by Treatment Group | White Blood Cell Count (x10^3/uL) < 2000/uL | 0 Participants |
| 50 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Hematology Results by Treatment Group | Eosinophils (x10^3/uL) > 5000/uL | 0 Participants |
| 50 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Hematology Results by Treatment Group | Hemoglobin (g/dL) < 8 g/dL | 0 Participants |
| 50 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Hematology Results by Treatment Group | Platelets (x10^3/uL) < 50,000/uL | 0 Participants |
| 50 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Hematology Results by Treatment Group | Neutrophils (x10^3/uL) < 1000/uL | 0 Participants |
| 50 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Hematology Results by Treatment Group | White Blood Cell Count (x10^3/uL) < 2000/uL | 0 Participants |
| 150 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Hematology Results by Treatment Group | Eosinophils (x10^3/uL) > 5000/uL | 0 Participants |
| 150 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Hematology Results by Treatment Group | White Blood Cell Count (x10^3/uL) < 2000/uL | 0 Participants |
| 150 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Hematology Results by Treatment Group | Neutrophils (x10^3/uL) < 1000/uL | 0 Participants |
| 150 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Hematology Results by Treatment Group | Hemoglobin (g/dL) < 8 g/dL | 0 Participants |
| 150 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Hematology Results by Treatment Group | Platelets (x10^3/uL) < 50,000/uL | 0 Participants |
| 300 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Hematology Results by Treatment Group | Hemoglobin (g/dL) < 8 g/dL | 0 Participants |
| 300 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Hematology Results by Treatment Group | Neutrophils (x10^3/uL) < 1000/uL | 0 Participants |
| 300 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Hematology Results by Treatment Group | White Blood Cell Count (x10^3/uL) < 2000/uL | 0 Participants |
| 300 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Hematology Results by Treatment Group | Eosinophils (x10^3/uL) > 5000/uL | 0 Participants |
| 300 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Hematology Results by Treatment Group | Platelets (x10^3/uL) < 50,000/uL | 0 Participants |
Primary
Part 1: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group
Number of Participants with Potentially Clinically Significant Vital Sign Measurements by Treatment Group. Percentages are based on the number of patients with at least one non-missing post-baseline value in each treatment group.
Time frame: 12 weeks
Population: Safety Population: Data from all enrolled subjects who were randomized in Part 1 and received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Part 1: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group | Systolic Blood Pressure Decrease of < -20 mmHg from baseline and <= 90 mmHg | 2 Participants |
| Placebo | Part 1: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group | Diastolic Blood Pressure Increase of > 15 mmHg from baseline and >= 105 mmHg | 0 Participants |
| Placebo | Part 1: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group | Pulse Decrease of < -15 bpm from baseline and <= 50 | 0 Participants |
| Placebo | Part 1: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group | Body Weight Decrease of < -7% lbs from baseline | 3 Participants |
| Placebo | Part 1: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group | Pulse Increase of > 15 bpm from baseline and >= 120 | 0 Participants |
| Placebo | Part 1: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group | Diastolic Blood Pressure Decrease of < -15 mmHg from baseline and <= 50 mmHg | 1 Participants |
| Placebo | Part 1: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group | Body Weight Increase of > 7% lbs from baseline | 0 Participants |
| Placebo | Part 1: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group | Systolic Blood Pressure Increase of > 20 mmHg from baseline and >= 180mmHg | 0 Participants |
| 50 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group | Body Weight Increase of > 7% lbs from baseline | 0 Participants |
| 50 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group | Pulse Increase of > 15 bpm from baseline and >= 120 | 1 Participants |
| 50 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group | Pulse Decrease of < -15 bpm from baseline and <= 50 | 0 Participants |
| 50 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group | Systolic Blood Pressure Decrease of < -20 mmHg from baseline and <= 90 mmHg | 0 Participants |
| 50 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group | Systolic Blood Pressure Increase of > 20 mmHg from baseline and >= 180mmHg | 2 Participants |
| 50 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group | Diastolic Blood Pressure Increase of > 15 mmHg from baseline and >= 105 mmHg | 1 Participants |
| 50 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group | Body Weight Decrease of < -7% lbs from baseline | 2 Participants |
| 50 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group | Diastolic Blood Pressure Decrease of < -15 mmHg from baseline and <= 50 mmHg | 1 Participants |
| 150 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group | Pulse Decrease of < -15 bpm from baseline and <= 50 | 0 Participants |
| 150 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group | Body Weight Increase of > 7% lbs from baseline | 0 Participants |
| 150 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group | Body Weight Decrease of < -7% lbs from baseline | 0 Participants |
| 150 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group | Systolic Blood Pressure Decrease of < -20 mmHg from baseline and <= 90 mmHg | 0 Participants |
| 150 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group | Diastolic Blood Pressure Increase of > 15 mmHg from baseline and >= 105 mmHg | 0 Participants |
| 150 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group | Systolic Blood Pressure Increase of > 20 mmHg from baseline and >= 180mmHg | 0 Participants |
| 150 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group | Diastolic Blood Pressure Decrease of < -15 mmHg from baseline and <= 50 mmHg | 0 Participants |
| 150 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group | Pulse Increase of > 15 bpm from baseline and >= 120 | 0 Participants |
| 300 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group | Body Weight Decrease of < -7% lbs from baseline | 1 Participants |
| 300 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group | Systolic Blood Pressure Increase of > 20 mmHg from baseline and >= 180mmHg | 0 Participants |
| 300 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group | Systolic Blood Pressure Decrease of < -20 mmHg from baseline and <= 90 mmHg | 0 Participants |
| 300 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group | Diastolic Blood Pressure Increase of > 15 mmHg from baseline and >= 105 mmHg | 0 Participants |
| 300 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group | Diastolic Blood Pressure Decrease of < -15 mmHg from baseline and <= 50 mmHg | 0 Participants |
| 300 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group | Pulse Increase of > 15 bpm from baseline and >= 120 | 0 Participants |
| 300 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group | Pulse Decrease of < -15 bpm from baseline and <= 50 | 1 Participants |
| 300 mg/Day | Part 1: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group | Body Weight Increase of > 7% lbs from baseline | 0 Participants |
Primary
Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group
Number of Participants with Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group. Percentages are based on the number of patients with at least one non-missing post-baseline value in each treatment group.
Time frame: 12 weeks
Population: Safety Population: Data from all enrolled subjects who were randomized in Part 1 and received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Myocardial Ischemia/Infarction Old Myocardial Infarction | 1 Participants |
| Placebo | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Rhythm Supraventricular | 0 Participants |
| Placebo | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Rhythm Atrial Flutter | 0 Participants |
| Placebo | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Rhythm Junctional Rhythm | 0 Participants |
| Placebo | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Conduction 3rd Degree A-V Block | 0 Participants |
| Placebo | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Rhythm Tachycardia > 100 bpm | 0 Participants |
| Placebo | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Rhythm Sinus Tachycardia > 120 bpm | 0 Participants |
| Placebo | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Conduction 2nd Degree A-V Block | 0 Participants |
| Placebo | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Rhythm Atrial Fibrillation | 0 Participants |
| Placebo | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Rhythm Torsades de Pointes | 0 Participants |
| Placebo | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Myocardial Ischemia/Infarction Acute or Subacute Myocardial Infarction | 0 Participants |
| Placebo | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Conduction 1st Degree A-V Block | 0 Participants |
| Placebo | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Rhythm Sinus Block/Sinus Arrest | 0 Participants |
| Placebo | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Myocardial Ischemia/Infarction Possible Myocardial Ischemia | 0 Participants |
| Placebo | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Conduction Pre-excitation (PR < 120 msec) | 0 Participants |
| Placebo | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Conduction Prolonged QTcF | 0 Participants |
| Placebo | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Myocardial Ischemia/Infarction Possible Myocardial Infarction | 3 Participants |
| Placebo | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Conduction Prolonged QTcB | 3 Participants |
| Placebo | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Conduction Right Bundle Branch Block | 0 Participants |
| Placebo | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Myocardial Ischemia/Infarction Myocardial Ischemia | 0 Participants |
| Placebo | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | U Wave Abnormal U wave present | 0 Participants |
| Placebo | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Rhythm Sinus Bradycardia < 40 bpm | 0 Participants |
| Placebo | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Conduction Left Bundle Branch Block | 0 Participants |
| Placebo | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Rhythm Other Ventricular Rhythm | 0 Participants |
| 50 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Conduction Left Bundle Branch Block | 0 Participants |
| 50 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Myocardial Ischemia/Infarction Myocardial Ischemia | 1 Participants |
| 50 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Myocardial Ischemia/Infarction Possible Myocardial Ischemia | 0 Participants |
| 50 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Myocardial Ischemia/Infarction Old Myocardial Infarction | 1 Participants |
| 50 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Myocardial Ischemia/Infarction Acute or Subacute Myocardial Infarction | 0 Participants |
| 50 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Rhythm Atrial Fibrillation | 0 Participants |
| 50 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Myocardial Ischemia/Infarction Possible Myocardial Infarction | 2 Participants |
| 50 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | U Wave Abnormal U wave present | 0 Participants |
| 50 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Rhythm Sinus Bradycardia < 40 bpm | 0 Participants |
| 50 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Rhythm Supraventricular | 0 Participants |
| 50 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Rhythm Tachycardia > 100 bpm | 0 Participants |
| 50 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Rhythm Sinus Tachycardia > 120 bpm | 0 Participants |
| 50 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Rhythm Torsades de Pointes | 0 Participants |
| 50 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Rhythm Other Ventricular Rhythm | 0 Participants |
| 50 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Rhythm Sinus Block/Sinus Arrest | 0 Participants |
| 50 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Conduction 1st Degree A-V Block | 1 Participants |
| 50 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Conduction 2nd Degree A-V Block | 0 Participants |
| 50 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Conduction 3rd Degree A-V Block | 0 Participants |
| 50 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Rhythm Junctional Rhythm | 0 Participants |
| 50 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Conduction Right Bundle Branch Block | 0 Participants |
| 50 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Conduction Pre-excitation (PR < 120 msec) | 0 Participants |
| 50 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Conduction Prolonged QTcB | 3 Participants |
| 50 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Conduction Prolonged QTcF | 0 Participants |
| 50 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Rhythm Atrial Flutter | 0 Participants |
| 150 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Rhythm Sinus Bradycardia < 40 bpm | 0 Participants |
| 150 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Conduction Prolonged QTcF | 0 Participants |
| 150 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Conduction 3rd Degree A-V Block | 0 Participants |
| 150 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Rhythm Supraventricular | 0 Participants |
| 150 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | U Wave Abnormal U wave present | 0 Participants |
| 150 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Rhythm Atrial Fibrillation | 0 Participants |
| 150 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Conduction Left Bundle Branch Block | 0 Participants |
| 150 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Conduction Prolonged QTcB | 1 Participants |
| 150 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Myocardial Ischemia/Infarction Possible Myocardial Infarction | 3 Participants |
| 150 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Rhythm Atrial Flutter | 0 Participants |
| 150 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Conduction Right Bundle Branch Block | 1 Participants |
| 150 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Rhythm Junctional Rhythm | 0 Participants |
| 150 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Myocardial Ischemia/Infarction Acute or Subacute Myocardial Infarction | 0 Participants |
| 150 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Myocardial Ischemia/Infarction Myocardial Ischemia | 0 Participants |
| 150 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Rhythm Other Ventricular Rhythm | 0 Participants |
| 150 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Conduction Pre-excitation (PR < 120 msec) | 0 Participants |
| 150 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Rhythm Torsades de Pointes | 0 Participants |
| 150 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Myocardial Ischemia/Infarction Old Myocardial Infarction | 0 Participants |
| 150 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Conduction 1st Degree A-V Block | 0 Participants |
| 150 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Rhythm Sinus Block/Sinus Arrest | 0 Participants |
| 150 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Rhythm Tachycardia > 100 bpm | 0 Participants |
| 150 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Myocardial Ischemia/Infarction Possible Myocardial Ischemia | 0 Participants |
| 150 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Conduction 2nd Degree A-V Block | 0 Participants |
| 150 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Rhythm Sinus Tachycardia > 120 bpm | 0 Participants |
| 300 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | U Wave Abnormal U wave present | 0 Participants |
| 300 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Rhythm Sinus Tachycardia > 120 bpm | 0 Participants |
| 300 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Rhythm Sinus Bradycardia < 40 bpm | 0 Participants |
| 300 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Rhythm Sinus Block/Sinus Arrest | 0 Participants |
| 300 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Rhythm Junctional Rhythm | 0 Participants |
| 300 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Rhythm Atrial Flutter | 0 Participants |
| 300 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Rhythm Atrial Fibrillation | 1 Participants |
| 300 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Rhythm Supraventricular | 0 Participants |
| 300 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Rhythm Tachycardia > 100 bpm | 0 Participants |
| 300 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Rhythm Torsades de Pointes | 0 Participants |
| 300 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Rhythm Other Ventricular Rhythm | 0 Participants |
| 300 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Conduction 1st Degree A-V Block | 0 Participants |
| 300 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Conduction 2nd Degree A-V Block | 0 Participants |
| 300 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Conduction 3rd Degree A-V Block | 0 Participants |
| 300 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Conduction Left Bundle Branch Block | 0 Participants |
| 300 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Conduction Right Bundle Branch Block | 0 Participants |
| 300 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Conduction Pre-excitation (PR < 120 msec) | 0 Participants |
| 300 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Conduction Prolonged QTcB | 3 Participants |
| 300 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Conduction Prolonged QTcF | 1 Participants |
| 300 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Myocardial Ischemia/Infarction Myocardial Ischemia | 0 Participants |
| 300 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Myocardial Ischemia/Infarction Possible Myocardial Ischemia | 1 Participants |
| 300 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Myocardial Ischemia/Infarction Old Myocardial Infarction | 0 Participants |
| 300 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Myocardial Ischemia/Infarction Acute or Subacute Myocardial Infarction | 0 Participants |
| 300 mg/Day | Part 1: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Myocardial Ischemia/Infarction Possible Myocardial Infarction | 0 Participants |
Secondary
Part 1: Slope of ALSFRS-R (ALS Functional Rating Scale With Respiratory Component) From Baseline to Week 12 by Treatment Group
The ALSFRS-R (ALS functional rating scale with respiratory component) is a validated scale which measures 4 functional domains, comprising respiratory function, bulbar function, gross motor skills, and fine motor skills. There are a total of 12 questions, each scored from 0 to 4 for a total possible score of 48, with higher scores representing better function. Slope is calculated using a linear mixed effects model with x-axis time in months and y-axis ALSFRS-R score. Units for slope are change per month in units on the ALSFRS-R scale.
Time frame: 12 weeks
Population: Randomized subjects who had at least 1 post-baseline clinical status evaluation within 7 days of discontinuing study drug
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Part 1: Slope of ALSFRS-R (ALS Functional Rating Scale With Respiratory Component) From Baseline to Week 12 by Treatment Group | -1.278 slope |
| 50 mg/Day | Part 1: Slope of ALSFRS-R (ALS Functional Rating Scale With Respiratory Component) From Baseline to Week 12 by Treatment Group | -1.885 slope |
| 150 mg/Day | Part 1: Slope of ALSFRS-R (ALS Functional Rating Scale With Respiratory Component) From Baseline to Week 12 by Treatment Group | -1.165 slope |
| 300 mg/Day | Part 1: Slope of ALSFRS-R (ALS Functional Rating Scale With Respiratory Component) From Baseline to Week 12 by Treatment Group | -0.878 slope |
p-value: 0.138595% CI: [-1.41, 0.19]Mixed Models Analysis
p-value: 0.771895% CI: [-0.65, 0.88]Mixed Models Analysis
p-value: 0.314695% CI: [-0.38, 1.18]Mixed Models Analysis
Secondary
Part 1: Slope of Upright Vital Capacity From Baseline to Week 12 by Treatment Group
Slope of change in Upright Vital Capacity (percent predicted upright vital capacity) from Baseline to Week 12. A negative change/slope indicates clinical worsening. Slope is calculated using a linear mixed effects model with x-axis time in months and y-axis as percent predicted upright vital capacity. Units for slope are change per month in percent predicted upright vital capacity.
Time frame: 12 weeks
Population: Randomized subjects who had at least 1 post-baseline clinical status evaluation with 7 days of discontinuing study drug
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Part 1: Slope of Upright Vital Capacity From Baseline to Week 12 by Treatment Group | -4.398 slope |
| 50 mg/Day | Part 1: Slope of Upright Vital Capacity From Baseline to Week 12 by Treatment Group | -4.003 slope |
| 150 mg/Day | Part 1: Slope of Upright Vital Capacity From Baseline to Week 12 by Treatment Group | -2.389 slope |
| 300 mg/Day | Part 1: Slope of Upright Vital Capacity From Baseline to Week 12 by Treatment Group | -3.947 slope |
p-value: 0.797395% CI: [-2.61, 3.4]Mixed Models Analysis
p-value: 0.173295% CI: [-0.87, 4.89]Mixed Models Analysis
p-value: 0.763595% CI: [-2.48, 3.39]Mixed Models Analysis
Secondary
Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group
Number of Participants with Potentially Clinically Significant Blood Chemistry Results by Treatment Group. Percentages based on number of patients with at least one non-missing post-baseline value in each treatment group. Patients are only counted once per criterion per parameter.
Time frame: up to 76 weeks
Population: Safety Population: Data from all enrolled subjects who were randomized in Part 1 and received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Alkaline Phosphatase (U/L) > 1.5xULN | 1 Participants |
| Placebo | Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Sodium (mEq/L) high > 157 mEq/L | 1 Participants |
| Placebo | Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Total Bilirubin (mg/dL) > 1.5xULN | 0 Participants |
| Placebo | Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Potassium (mEq/L) Low < 2.5 mEq/L | 0 Participants |
| Placebo | Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | BUN (mg/dL) > 5xULN | 0 Participants |
| Placebo | Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Potassium (mEq/L) High > 6.5 mEq/L | 0 Participants |
| Placebo | Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | AST (SGOT) (U/L) > 3xULN | 1 Participants |
| Placebo | Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Glucose (mg/dL) Low < 40 mg/dL | 0 Participants |
| Placebo | Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Creatinine (mg/dL) > 3xULN | 0 Participants |
| Placebo | Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Glucose (mg/dL) High > 250 mg/dL | 1 Participants |
| Placebo | Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | ALT (SGPT) (U/L) > 3xULN | 1 Participants |
| Placebo | Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Calcium (mg/dL) Low < 7 mg/dL | 0 Participants |
| Placebo | Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Sodium (mEq/L) low < 123 mEq/L | 0 Participants |
| Placebo | Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Calcium (mg/dL) High > 12.5 mg/dL | 0 Participants |
| Placebo | Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Creatine Kinase (U/L) >= 10xULN | 0 Participants |
| 50 mg/Day | Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Calcium (mg/dL) High > 12.5 mg/dL | 0 Participants |
| 50 mg/Day | Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Creatine Kinase (U/L) >= 10xULN | 0 Participants |
| 50 mg/Day | Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Total Bilirubin (mg/dL) > 1.5xULN | 0 Participants |
| 50 mg/Day | Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | ALT (SGPT) (U/L) > 3xULN | 2 Participants |
| 50 mg/Day | Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | AST (SGOT) (U/L) > 3xULN | 0 Participants |
| 50 mg/Day | Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Alkaline Phosphatase (U/L) > 1.5xULN | 1 Participants |
| 50 mg/Day | Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | BUN (mg/dL) > 5xULN | 0 Participants |
| 50 mg/Day | Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Creatinine (mg/dL) > 3xULN | 0 Participants |
| 50 mg/Day | Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Sodium (mEq/L) low < 123 mEq/L | 0 Participants |
| 50 mg/Day | Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Sodium (mEq/L) high > 157 mEq/L | 0 Participants |
| 50 mg/Day | Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Potassium (mEq/L) Low < 2.5 mEq/L | 1 Participants |
| 50 mg/Day | Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Potassium (mEq/L) High > 6.5 mEq/L | 0 Participants |
| 50 mg/Day | Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Glucose (mg/dL) Low < 40 mg/dL | 0 Participants |
| 50 mg/Day | Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Glucose (mg/dL) High > 250 mg/dL | 1 Participants |
| 50 mg/Day | Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group | Calcium (mg/dL) Low < 7 mg/dL | 1 Participants |
Secondary
Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Hematology Results by Treatment Group
Number of Participants with Potentially Clinically Significant Hematology Results by Treatment Group. Percentages based on number of patients with at least one non-missing post-baseline value in each treatment group. Patients are only counted once per criterion per parameter.
Time frame: up to 76 weeks
Population: Safety Population: Data from all enrolled subjects who were randomized in Part 1 and received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Hematology Results by Treatment Group | Neutrophils (x10^3/uL) < 1000/uL | 0 Participants |
| Placebo | Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Hematology Results by Treatment Group | Hemoglobin (g/dL) < 8 g/dL | 0 Participants |
| Placebo | Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Hematology Results by Treatment Group | Eosinophils (x10^3/uL) > 5000/uL | 0 Participants |
| Placebo | Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Hematology Results by Treatment Group | Platelets (x10^3/uL) < 50,000/uL | 0 Participants |
| Placebo | Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Hematology Results by Treatment Group | White Blood Cell Count (x10^3/uL) < 2000/uL | 0 Participants |
| 50 mg/Day | Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Hematology Results by Treatment Group | Platelets (x10^3/uL) < 50,000/uL | 0 Participants |
| 50 mg/Day | Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Hematology Results by Treatment Group | White Blood Cell Count (x10^3/uL) < 2000/uL | 0 Participants |
| 50 mg/Day | Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Hematology Results by Treatment Group | Neutrophils (x10^3/uL) < 1000/uL | 0 Participants |
| 50 mg/Day | Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Hematology Results by Treatment Group | Eosinophils (x10^3/uL) > 5000/uL | 0 Participants |
| 50 mg/Day | Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Hematology Results by Treatment Group | Hemoglobin (g/dL) < 8 g/dL | 1 Participants |
Secondary
Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group
Number of Participants with Potentially Clinically Significant Vital Sign Measurements by Treatment Group. Percentages based on number of patients with at least one non-missing post-baseline value in each treatment group. Patients are only counted once per criterion per parameter.
Time frame: up to 76 weeks
Population: Safety Population: Data from all enrolled subjects who were randomized in Part 1, received at least 1 dose of study drug, and had at least one post baseline evaluation.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group | Systolic Blood Pressure Increase of > 20 mmHg from baseline and >= 180mmHg | 0 Participants |
| Placebo | Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group | Systolic Blood Pressure Decrease of < -20 mmHg from baseline and <= 90 mmHg | 0 Participants |
| Placebo | Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group | Diastolic Blood Pressure Increase of > 15 mmHg from baseline and >= 105 mmHg | 2 Participants |
| Placebo | Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group | Diastolic Blood Pressure Decrease of < -15 mmHg from baseline and <= 50 mmHg | 3 Participants |
| Placebo | Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group | Pulse Increase of > 15 bpm from baseline and >= 120 | 1 Participants |
| Placebo | Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group | Pulse Decrease of < -15 bpm from baseline and <= 50 | 0 Participants |
| Placebo | Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group | Body Weight Increase of > 7% lbs from baseline | 1 Participants |
| Placebo | Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group | Body Weight Decrease of < -7% lbs from baseline | 14 Participants |
| 50 mg/Day | Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group | Body Weight Decrease of < -7% lbs from baseline | 16 Participants |
| 50 mg/Day | Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group | Systolic Blood Pressure Increase of > 20 mmHg from baseline and >= 180mmHg | 0 Participants |
| 50 mg/Day | Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group | Pulse Increase of > 15 bpm from baseline and >= 120 | 2 Participants |
| 50 mg/Day | Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group | Systolic Blood Pressure Decrease of < -20 mmHg from baseline and <= 90 mmHg | 1 Participants |
| 50 mg/Day | Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group | Body Weight Increase of > 7% lbs from baseline | 1 Participants |
| 50 mg/Day | Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group | Diastolic Blood Pressure Increase of > 15 mmHg from baseline and >= 105 mmHg | 1 Participants |
| 50 mg/Day | Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group | Pulse Decrease of < -15 bpm from baseline and <= 50 | 0 Participants |
| 50 mg/Day | Part 2 Double-Blind Treatment: Number of Participants With Potentially Clinically Significant Vital Sign Measurements by Treatment Group | Diastolic Blood Pressure Decrease of < -15 mmHg from baseline and <= 50 mmHg | 1 Participants |
Secondary
Part 2 Double-Blind Treatment: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group
Number of Participants with Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group. Percentages based on number of patients with at least one non-missing post-baseline value in each treatment group. Patients are only counted once per criterion per parameter.
Time frame: up to 76 weeks
Population: Safety Population: Data from all enrolled subjects who were randomized in Part 2, received at least 1 dose of study drug, and had at least one evaluation post baseline.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Part 2 Double-Blind Treatment: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Rhythm Supraventricular | 0 Participants |
| Placebo | Part 2 Double-Blind Treatment: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Rhythm Sinus Bradycardia < 40 bpm | 0 Participants |
| Placebo | Part 2 Double-Blind Treatment: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Rhythm Sinus Block/Sinus Arrest | 0 Participants |
| Placebo | Part 2 Double-Blind Treatment: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Rhythm Junctional Rhythm | 0 Participants |
| Placebo | Part 2 Double-Blind Treatment: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Rhythm Atrial Flutter | 0 Participants |
| Placebo | Part 2 Double-Blind Treatment: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Rhythm Atrial Fibrillation | 0 Participants |
| Placebo | Part 2 Double-Blind Treatment: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Rhythm Sinus Tachycardia > 120 bpm | 2 Participants |
| Placebo | Part 2 Double-Blind Treatment: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Rhythm Tachycardia > 100 bpm | 0 Participants |
| Placebo | Part 2 Double-Blind Treatment: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Rhythm Torsades de Pointes | 0 Participants |
| Placebo | Part 2 Double-Blind Treatment: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Rhythm Other Ventricular Rhythm | 0 Participants |
| Placebo | Part 2 Double-Blind Treatment: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Conduction 1st Degree A-V Block | 2 Participants |
| Placebo | Part 2 Double-Blind Treatment: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Conduction 2nd Degree A-V Block | 0 Participants |
| Placebo | Part 2 Double-Blind Treatment: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Conduction 3rd Degree A-V Block | 0 Participants |
| Placebo | Part 2 Double-Blind Treatment: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Conduction Left Bundle Branch Block | 0 Participants |
| Placebo | Part 2 Double-Blind Treatment: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Conduction Right Bundle Branch Block | 1 Participants |
| Placebo | Part 2 Double-Blind Treatment: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Conduction Pre-excitation (PR < 120 msec) | 0 Participants |
| Placebo | Part 2 Double-Blind Treatment: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Conduction Prolonged QTcB | 6 Participants |
| Placebo | Part 2 Double-Blind Treatment: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Conduction Prolonged QTcF | 1 Participants |
| Placebo | Part 2 Double-Blind Treatment: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Myocardial Ischemia/Infarction Myocardial Ischemia | 0 Participants |
| Placebo | Part 2 Double-Blind Treatment: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Myocardial Ischemia/Infarction Possible Myocardial Ischemia | 1 Participants |
| Placebo | Part 2 Double-Blind Treatment: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Myocardial Ischemia/Infarction Old Myocardial Infarction | 3 Participants |
| Placebo | Part 2 Double-Blind Treatment: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Myocardial Ischemia/Infarction Acute or Subacute Myocardial Infarction | 0 Participants |
| Placebo | Part 2 Double-Blind Treatment: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Myocardial Ischemia/Infarction Possible Myocardial Infarction | 4 Participants |
| Placebo | Part 2 Double-Blind Treatment: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | U Wave Abnormal U wave present | 0 Participants |
| 50 mg/Day | Part 2 Double-Blind Treatment: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Myocardial Ischemia/Infarction Possible Myocardial Infarction | 2 Participants |
| 50 mg/Day | Part 2 Double-Blind Treatment: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Rhythm Sinus Tachycardia > 120 bpm | 0 Participants |
| 50 mg/Day | Part 2 Double-Blind Treatment: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Conduction 3rd Degree A-V Block | 0 Participants |
| 50 mg/Day | Part 2 Double-Blind Treatment: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Rhythm Sinus Bradycardia < 40 bpm | 0 Participants |
| 50 mg/Day | Part 2 Double-Blind Treatment: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Myocardial Ischemia/Infarction Myocardial Ischemia | 0 Participants |
| 50 mg/Day | Part 2 Double-Blind Treatment: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Rhythm Sinus Block/Sinus Arrest | 0 Participants |
| 50 mg/Day | Part 2 Double-Blind Treatment: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Conduction Left Bundle Branch Block | 0 Participants |
| 50 mg/Day | Part 2 Double-Blind Treatment: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Rhythm Junctional Rhythm | 1 Participants |
| 50 mg/Day | Part 2 Double-Blind Treatment: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Myocardial Ischemia/Infarction Acute or Subacute Myocardial Infarction | 0 Participants |
| 50 mg/Day | Part 2 Double-Blind Treatment: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Rhythm Atrial Flutter | 0 Participants |
| 50 mg/Day | Part 2 Double-Blind Treatment: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Conduction Right Bundle Branch Block | 2 Participants |
| 50 mg/Day | Part 2 Double-Blind Treatment: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Rhythm Atrial Fibrillation | 1 Participants |
| 50 mg/Day | Part 2 Double-Blind Treatment: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Myocardial Ischemia/Infarction Possible Myocardial Ischemia | 0 Participants |
| 50 mg/Day | Part 2 Double-Blind Treatment: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Rhythm Supraventricular | 0 Participants |
| 50 mg/Day | Part 2 Double-Blind Treatment: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Conduction Pre-excitation (PR < 120 msec) | 0 Participants |
| 50 mg/Day | Part 2 Double-Blind Treatment: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Rhythm Tachycardia > 100 bpm | 0 Participants |
| 50 mg/Day | Part 2 Double-Blind Treatment: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | U Wave Abnormal U wave present | 0 Participants |
| 50 mg/Day | Part 2 Double-Blind Treatment: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Rhythm Torsades de Pointes | 0 Participants |
| 50 mg/Day | Part 2 Double-Blind Treatment: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Conduction Prolonged QTcB | 3 Participants |
| 50 mg/Day | Part 2 Double-Blind Treatment: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Rhythm Other Ventricular Rhythm | 0 Participants |
| 50 mg/Day | Part 2 Double-Blind Treatment: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Myocardial Ischemia/Infarction Old Myocardial Infarction | 2 Participants |
| 50 mg/Day | Part 2 Double-Blind Treatment: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Conduction 1st Degree A-V Block | 2 Participants |
| 50 mg/Day | Part 2 Double-Blind Treatment: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Conduction Prolonged QTcF | 1 Participants |
| 50 mg/Day | Part 2 Double-Blind Treatment: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group | Conduction 2nd Degree A-V Block | 0 Participants |
Secondary
Part 2 Double-Blind Treatment: Slope of Percent Predicted Upright Vital Capacity From Baseline by Treatment Group
Slope of Upright Vital Capacity (percent predicted) through Week 28. A negative change indicates clinical worsening. Slope is calculated using a linear mixed effects model with x-axis time in months and y-axis percent predicted upright vital capacity. Units for slope are change per month in percent predicted upright vital capacity.
Time frame: Baseline of randomized phase of Part 2 to week 28 of randomized phase of Part 2
Population: Randomized subjects who had at least 1 post-baseline clinical status evaluation with 7 days of discontinuing study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Part 2 Double-Blind Treatment: Slope of Percent Predicted Upright Vital Capacity From Baseline by Treatment Group | -2.452 slope |
| 50 mg/Day | Part 2 Double-Blind Treatment: Slope of Percent Predicted Upright Vital Capacity From Baseline by Treatment Group | -3.067 slope |
p-value: 0.402595% CI: [-2.06, 0.83]Mixed Models Analysis
Secondary
Part 2 Double-Blind Treatment: Slope of the ALSFRS-R (ALS Functional Rating Scale With Respiratory Component) From Baseline to Week 28 by Treatment Group
The ALSFRS-R (ALS functional rating scale with respiratory component) is a validated scale which measures 4 functional domains, comprising respiratory function, bulbar function, gross motor skills, and fine motor skills. There are a total of 12 questions, each scored from 0 to 4 for a total possible score of 48, with higher scores representing better function. Slope is calculated using a linear mixed effects model with x-axis time in months and y-axis ALSFRS-R score. Units for slope are change per month n units on the ALSFRS-R scale.
Time frame: 28 weeks
Population: Randomized subjects who had at least 1 post-baseline clinical status evaluation with 7 days of discontinuing study drug
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Part 2 Double-Blind Treatment: Slope of the ALSFRS-R (ALS Functional Rating Scale With Respiratory Component) From Baseline to Week 28 by Treatment Group | -1.284 slope |
| 50 mg/Day | Part 2 Double-Blind Treatment: Slope of the ALSFRS-R (ALS Functional Rating Scale With Respiratory Component) From Baseline to Week 28 by Treatment Group | -1.021 slope |
p-value: 0.177295% CI: [-0.12, 0.64]Mixed Models Analysis
Secondary
Part 2 Placebo Washout: Absolute Change in ALSFRS-R Total Score
The ALSFRS-R (ALS functional rating scale with respiratory component) is a validated scale which measures 4 functional domains, comprising respiratory function, bulbar function, gross motor skills, and fine motor skills. There are a total of 12 questions, each scored from 0 to 4 for a total possible score of 48, with higher scores representing better function. Units are points on the ALSFRS-R score as an absolute change from the baseline of the placebo washout to week 4 of the placebo washout.
Time frame: 4 weeks
Population: Randomized subjects who had at least 1 post-baseline clinical status evaluation with 7 days of discontinuing study drug
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Part 2 Placebo Washout: Absolute Change in ALSFRS-R Total Score | -1.2 units on a scale | Standard Error 0.27 |
Secondary
Part 2 Placebo Washout: Absolute Change in Upright Vital Capacity (Percent Predicted) From Baseline to End of Placebo Washout (Week 4)
Absolute change in Upright Vital Capacity From Baseline to Week 4. Units are percent of predicted Upright Vital Capacity. A negative change indicates clinical worsening.
Time frame: 4 weeks
Population: Randomized subjects who had at least 1 post-baseline clinical status evaluation with 7 days of discontinuing study drug
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Part 2 Placebo Washout: Absolute Change in Upright Vital Capacity (Percent Predicted) From Baseline to End of Placebo Washout (Week 4) | -3.1 units on a scale | Standard Error 0.95 |
Secondary
Part 2 Placebo Washout: Number of Participants With Potentially Clinically Significant Blood Chemistry Results
Number of Participants with Potentially Clinically Significant Blood Chemistry Results by Treatment Group. Percentages based on number of patients with at least one non-missing post-baseline value in each treatment group. Patients are only counted once per criterion per laboratory test.
Time frame: 4 weeks
Population: Safety Population: Data from all enrolled subjects who were randomized in Part 2, received at least 1 dose of study drug, and had one post BL evaluation during the placebo washout.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Part 2 Placebo Washout: Number of Participants With Potentially Clinically Significant Blood Chemistry Results | Total Bilirubin (mg/dL) > 1.5xULN | 0 Participants |
| Placebo | Part 2 Placebo Washout: Number of Participants With Potentially Clinically Significant Blood Chemistry Results | Creatine Kinase (U/L) >= 10xULN | 0 Participants |
| Placebo | Part 2 Placebo Washout: Number of Participants With Potentially Clinically Significant Blood Chemistry Results | ALT (SGPT) (U/L) > 3xULN | 0 Participants |
| Placebo | Part 2 Placebo Washout: Number of Participants With Potentially Clinically Significant Blood Chemistry Results | AST (SGOT) (U/L) > 3xULN | 0 Participants |
| Placebo | Part 2 Placebo Washout: Number of Participants With Potentially Clinically Significant Blood Chemistry Results | Alkaline Phosphatase (U/L) > 1.5xULN | 0 Participants |
| Placebo | Part 2 Placebo Washout: Number of Participants With Potentially Clinically Significant Blood Chemistry Results | BUN (mg/dL) > 5xULN | 0 Participants |
| Placebo | Part 2 Placebo Washout: Number of Participants With Potentially Clinically Significant Blood Chemistry Results | Creatinine (mg/dL) > 3xULN | 0 Participants |
| Placebo | Part 2 Placebo Washout: Number of Participants With Potentially Clinically Significant Blood Chemistry Results | Sodium (mEq/L) low < 123 mEq/L | 0 Participants |
| Placebo | Part 2 Placebo Washout: Number of Participants With Potentially Clinically Significant Blood Chemistry Results | Sodium (mEq/L) high > 157 mEq/L | 0 Participants |
| Placebo | Part 2 Placebo Washout: Number of Participants With Potentially Clinically Significant Blood Chemistry Results | Potassium (mEq/L) Low < 2.5 mEq/L | 0 Participants |
| Placebo | Part 2 Placebo Washout: Number of Participants With Potentially Clinically Significant Blood Chemistry Results | Potassium (mEq/L) High > 6.5 mEq/L | 0 Participants |
| Placebo | Part 2 Placebo Washout: Number of Participants With Potentially Clinically Significant Blood Chemistry Results | Glucose (mg/dL) Low < 40 mg/dL | 0 Participants |
| Placebo | Part 2 Placebo Washout: Number of Participants With Potentially Clinically Significant Blood Chemistry Results | Glucose (mg/dL) High > 250 mg/dL | 0 Participants |
| Placebo | Part 2 Placebo Washout: Number of Participants With Potentially Clinically Significant Blood Chemistry Results | Calcium (mg/dL) Low < 7 mg/dL | 0 Participants |
| Placebo | Part 2 Placebo Washout: Number of Participants With Potentially Clinically Significant Blood Chemistry Results | Calcium (mg/dL) High > 12.5 mg/dL | 0 Participants |
Secondary
Part 2 Placebo Washout: Number of Participants With Potentially Clinically Significant Hematology
Number of Participants with Potentially Clinically Significant Hematology Results by Treatment Group. Percentages based on number of patients with at least one non-missing post-baseline value in each treatment group. Patients are only counted once per criterion per laboratory test.
Time frame: 4 weeks
Population: Safety Population: Data from all enrolled subjects who were randomized in Part 1 and received at least 1 dose of study drug during the placebo washout.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Part 2 Placebo Washout: Number of Participants With Potentially Clinically Significant Hematology | White Blood Cell Count (x10^3/uL) < 2000/uL | 0 Participants |
| Placebo | Part 2 Placebo Washout: Number of Participants With Potentially Clinically Significant Hematology | Neutrophils (x10^3/uL) < 1000/uL | 0 Participants |
| Placebo | Part 2 Placebo Washout: Number of Participants With Potentially Clinically Significant Hematology | Eosinophils (x10^3/uL) > 5000/uL | 0 Participants |
| Placebo | Part 2 Placebo Washout: Number of Participants With Potentially Clinically Significant Hematology | Hemoglobin (g/dL) < 8 g/dL | 0 Participants |
| Placebo | Part 2 Placebo Washout: Number of Participants With Potentially Clinically Significant Hematology | Platelets (x10^3/uL) < 50,000/uL | 0 Participants |
Secondary
Part 2 Placebo Washout: Number of Participants With Potentially Clinically Significant Vital Sign Measurements
Number of Participants with Potentially Clinically Significant Vital Sign Measurements by Treatment Group. Percentages are based on the number of patients with at least one non-missing post-baseline value in each treatment group.
Time frame: 4 weeks
Population: Safety Population: Data from all enrolled subjects who were randomized in Part 1 and received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Part 2 Placebo Washout: Number of Participants With Potentially Clinically Significant Vital Sign Measurements | Systolic Blood Pressure Increase of > 20 mmHg from baseline and >= 180mmHg | 0 Participants |
| Placebo | Part 2 Placebo Washout: Number of Participants With Potentially Clinically Significant Vital Sign Measurements | Systolic Blood Pressure Decrease of < -20 mmHg from baseline and <= 90 mmHg | 0 Participants |
| Placebo | Part 2 Placebo Washout: Number of Participants With Potentially Clinically Significant Vital Sign Measurements | Diastolic Blood Pressure Increase of > 15 mmHg from baseline and >= 105 mmHg | 2 Participants |
| Placebo | Part 2 Placebo Washout: Number of Participants With Potentially Clinically Significant Vital Sign Measurements | Diastolic Blood Pressure Decrease of < -15 mmHg from baseline and <= 50 mmHg | 0 Participants |
| Placebo | Part 2 Placebo Washout: Number of Participants With Potentially Clinically Significant Vital Sign Measurements | Pulse Increase of > 15 bpm from baseline and >= 120 | 1 Participants |
| Placebo | Part 2 Placebo Washout: Number of Participants With Potentially Clinically Significant Vital Sign Measurements | Pulse Decrease of < -15 bpm from baseline and <= 50 | 1 Participants |
| Placebo | Part 2 Placebo Washout: Number of Participants With Potentially Clinically Significant Vital Sign Measurements | Body Weight Increase of > 7% lbs from baseline | 0 Participants |
| Placebo | Part 2 Placebo Washout: Number of Participants With Potentially Clinically Significant Vital Sign Measurements | Body Weight Decrease of < -7% lbs from baseline | 0 Participants |
Secondary
Part 2 Placebo Washout: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings
Number of Participants with Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings by Treatment Group. Percentages are based on the number of patients with at least one non-missing post-baseline value in each treatment group.
Time frame: 4 weeks
Population: Safety Population: Data from all enrolled subjects who were randomized in Part 1, received at least 1 dose of study drug, and have at least on evaluation post baseline.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Part 2 Placebo Washout: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings | Rhythm Sinus Tachycardia > 120 bpm | 0 Participants |
| Placebo | Part 2 Placebo Washout: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings | Rhythm Sinus Bradycardia < 40 bpm | 0 Participants |
| Placebo | Part 2 Placebo Washout: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings | Rhythm Sinus Block/Sinus Arrest | 0 Participants |
| Placebo | Part 2 Placebo Washout: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings | Rhythm Junctional Rhythm | 0 Participants |
| Placebo | Part 2 Placebo Washout: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings | Rhythm Atrial Flutter | 0 Participants |
| Placebo | Part 2 Placebo Washout: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings | Rhythm Atrial Fibrillation | 0 Participants |
| Placebo | Part 2 Placebo Washout: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings | Rhythm Supraventricular | 0 Participants |
| Placebo | Part 2 Placebo Washout: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings | Rhythm Tachycardia > 100 bpm | 0 Participants |
| Placebo | Part 2 Placebo Washout: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings | Rhythm Torsades de Pointes | 0 Participants |
| Placebo | Part 2 Placebo Washout: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings | Rhythm Other Ventricular Rhythm | 0 Participants |
| Placebo | Part 2 Placebo Washout: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings | Conduction 1st Degree A-V Block | 2 Participants |
| Placebo | Part 2 Placebo Washout: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings | Conduction 2nd Degree A-V Block | 0 Participants |
| Placebo | Part 2 Placebo Washout: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings | Conduction 3rd Degree A-V Block | 0 Participants |
| Placebo | Part 2 Placebo Washout: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings | Conduction Left Bundle Branch Block | 0 Participants |
| Placebo | Part 2 Placebo Washout: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings | Conduction Right Bundle Branch Block | 2 Participants |
| Placebo | Part 2 Placebo Washout: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings | Conduction Pre-excitation (PR < 120 msec) | 0 Participants |
| Placebo | Part 2 Placebo Washout: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings | Conduction Prolonged QTcB | 4 Participants |
| Placebo | Part 2 Placebo Washout: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings | Conduction Prolonged QTcF | 3 Participants |
| Placebo | Part 2 Placebo Washout: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings | Myocardial Ischemia/Infarction Myocardial Ischemia | 0 Participants |
| Placebo | Part 2 Placebo Washout: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings | Myocardial Ischemia/Infarction Possible Myocardial Ischemia | 2 Participants |
| Placebo | Part 2 Placebo Washout: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings | Myocardial Ischemia/Infarction Old Myocardial Infarction | 4 Participants |
| Placebo | Part 2 Placebo Washout: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings | Myocardial Ischemia/Infarction Acute or Subacute Myocardial Infarction | 0 Participants |
| Placebo | Part 2 Placebo Washout: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings | Myocardial Ischemia/Infarction Possible Myocardial Infarction | 4 Participants |
| Placebo | Part 2 Placebo Washout: Number of Participants With Treatment Emergent Potentially Clinically Significant Electrocardiogram (ECG) Findings | U Wave Abnormal U wave present | 0 Participants |