Spinal Muscular Atrophy
Conditions
Keywords
Reldesemtiv
Brief summary
This study will evaluate the pharmacodynamic (PD) effect of CK-2127107 (hereafter referred to as reldesemtiv) versus placebo on measures of skeletal muscle function or fatigability in patients with Type II, III, or IV spinal muscular atrophy (SMA).
Detailed description
CY 5021 is a Phase 2, double-blind, randomized, placebo-controlled, multiple dose study of reldesemtiv in 2 sequential ascending dose cohorts of patients with SMA. Patients will be randomized 2:1 to receive reldesemtiv or placebo twice daily for 8 weeks. Patients randomized to reldesemtiv in Cohort 1 will receive a dose of 150 mg twice daily and patients randomized to reldesemtiv in Cohort 2 will receive 450 mg twice daily. Within each cohort, randomization will be stratified by ambulatory status (ambulatory versus non ambulatory). The primary objective of the study is to determine the PD effects of reldesemtiv on measures of pulmonary function, respiratory function, muscle strength, and motor function. Other PD measures include changes in the timed up and go (TUG) test, a 6-minute walk test (6MWT), and patient and investigator global assessments. Secondary objectives include the safety of multiple doses of reldesemtiv and an evaluation of the pharmacokinetics of reldesemtiv.
Interventions
DRUGPlacebo
Granules for oral suspension (placebo)
DRUGReldesemtiv 150 mg
Granules for oral suspension, 18.7% reldesemtiv
DRUGReldesemtiv 450 mg
Granules for oral suspension, 56.0% reldesemtiv
Sponsors
Astellas Pharma Global Development, Inc.
Cytokinetics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Able to comprehend and willing to sign an Informed Consent Form (ICF) for patients 18 years of age and older. For patients less than 18 years of age, parent(s)/legal guardian(s) of patients must provide written informed consent prior to participation in the study and informed assent will be obtained from minors at least 12 years of age when required by regulation. * Males or females with genetically confirmed diagnosis of SMA who are Type II, III or IV and at least 12 years of age * Ambulatory patients, once having achieved a standing position independently, must be able to complete at least one lap in the 6-minute walk test (at least 50 meters) within 6 minutes without assistance. * Non-ambulatory patients (defined as individuals who are effectively requiring a wheelchair for all mobility needs; they may be able to stand or walk short distances, but unable to walk 50 meters without assistance in 6 minutes). Non-ambulatory patients must be able to tolerate an upright sitting position, with support, continuously for 3 hours * Hammersmith (HFMS-E) score ≥ 10 and ≤ 54 * Contracture of the elbow flexion and knee flexion ≤ 90 degrees * Pre-study clinical laboratory findings within the normal range or, if outside the normal range, deemed not clinically significant by the Investigator * Able to swallow an oral suspension and in the opinion of the Investigator, is expected to continue to be able to do so for the duration of the trial. Administration via a feeding tube is not allowed. * Forced vital capacity (FVC) \> 20% predicted * Male patients who have reached puberty must agree to do either of the following from Screening until 10 weeks after the last dose of the investigational product unless they have had a vasectomy and confirmed sperm count is zero: * Abstain from sexual intercourse, OR * If having heterosexual intercourse, must use a condom and their female partners who are of childbearing potential must use a highly effective contraception method\* * Female patients who have had their first period will be considered of childbearing potential unless they are anatomically and physiologically incapable of becoming pregnant. If of childbearing potential, the female patients must: * Have a negative urine/serum pregnancy test at Screening AND * Abstain from heterosexual intercourse from Screening until 10 weeks after the last dose of investigational product OR * If having heterosexual intercourse, must use a highly effective contraception method\* and require the male partners to use a condom from Screening until 10 weeks after the last dose of investigational product \*Highly effective contraception methods include: * Established use of oral, injected or implanted hormonal methods of contraception * Placement of an intrauterine device (IUD) or intrauterine system (IUS) * Male patients must agree to refrain from sperm donation from Screening until 10 weeks after the final study drug administration
Exclusion criteria
* History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator * Hospitalization within 2 months of Screening * History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs (appendectomy, hernia repair, and/or cholecystectomy will be allowed) * A clinically significant illness within 4 weeks of Screening * History of alcoholism or drug addiction within 2 years prior to Screening * History of smoking more than 10 cigarettes (or equivalent amount of tobacco) per day within 3 months prior to Screening * Patient has used a strong CYP3A4 inhibitor within 7 days prior to first dose of study drug or a strong CYP3A4 inducer within 14 days prior to first dose of study drug * Any other medical condition that would interfere with performance of testing including (but not limited to) significant joint pain or arthritis limiting mobility, and chronic neuromuscular pain sufficient to require ongoing analgesic medication * Participation by two people at the same time that are living in the same household * Participation in any other investigational study drug trial in which receipt of an investigational study drug occurred within 30 days or five half-lives of the other investigational study drug, whichever is greater, prior to Screening * An ALT or AST greater than 2-fold the upper limit of normal (ULN) or has total bilirubin greater than the ULN at screening. These assessments may be repeated once at the investigator's discretion (within the screening window) * Currently taking nusinersen, or has taken it in the past, or plans to take it during the course the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Investigator Global Assessment at the End of Week 8 | 8 weeks | The Investigator assessed whether patient appeared the same, better, or worse than prior to dosing on Day 1. |
| Change From Baseline to Week 8 in the 6MWT | baseline and 8 weeks | The 6MWT measured the distance (in meters) a patient walked in 6 minutes. |
| Patient Global Assessment at the End of Week 8 | 8 weeks | Patients assessed whether they felt the same, better, or worse than prior to dosing on Day 1. |
| Change From Baseline to Week 8 in Forced Vital Capacity (FVC) | baseline and 8 weeks | FVC was measured using a calibrated spirometer (in units of liters). Patients were instructed to take as deep an inspiration as possible followed by a maximum exhalation (blowing out all the air in their lungs). |
| Change From Baseline to Week 8 in Maximum Inspiratory Pressure (MIP) | baseline and 8 weeks | MIP was measured (in units of cm H20) using a calibrated spirometer with an inspiratory pressure valve attached. For the test, patients were asked to inhale as forcefully as possible, to their maximum pressure. |
| Change From Baseline to Week 8 in Maximum Expiratory Pressure (MEP) | baseline and 8 weeks | MEP was measured (in units of cm H20) using a calibrated spirometer with an exspiratory pressure valve attached. For the test, patients were asked to maximally inhale then perform a forced exhalation with as forcefully as possible. |
| Muscle Strength Mega-Score at Week 8 | baseline and 8 weeks | Muscle strength of 3 muscle groups (elbow flexion, knee extension, and shoulder abduction) were measured bilaterally using a hand-held dynamometer. Muscle strength was measured twice for each body location; if the variability between the 2 measures was \> 15%, a third measure was obtained. The maximum muscle strength of the 2 measurements was identified and transformed as a percent change from baseline using the equation: (\[postbaseline value - baseline value\] / baseline value) × 100. The mega-score was a composite score that averaged strength across the 3 muscle groups. It was calculated as the mean of the non-missing transformed muscle strength scores among the 3 muscle groups each measure bilaterally (totaling 6 body locations). |
| Change From Baseline to Week 8 in the Hammersmith Functional Motor Scale-Expanded (HFMS-E) | baseline and 8 weeks | The HFMS-E evaluated the level of independent mobility and motor skills through assessment of 33 test-items, each scored from 0 (worse) to 2 (better). The total score was calculated as the sum of the scores among the 33 test items, and has a range from 0 to 66. |
| Change From Baseline to Week 8 in Revised Upper Limb Module (RULM) | baseline and 8 weeks | The RULM assessed motor function in the upper limbs (specifically shoulder, elbow, wrist, and hand function) that related to activities of everyday life. The RULM consisted of 20 items, 1 of which was scored on a 7-point scale (from 0 to 6), 18 were scored on a 3-point scale (from 0 to 2), and 1 was scored on a 2-point scale (0 or 1). The total score was the sum of each response and could range from a minimum of 0 to a maximum of 43 points. Higher scores reflected better motor function. |
| Change From Baseline to Week 8 in the TUG Test | baseline and 8 weeks | The TUG test measured the time (in seconds) it took for a patient to rise from a chair, walk 3 meters, turn around, walk back to the chair and sit down. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Reldesemtiv Area Under the Plasma Concentration-time Curve From 0 to 12 Hours (AUC0-12) | End of Week 8 | Determined by evaluation of reldesemtiv plasma concentrations from blood samples collected prior to dosing and at 1, 3, and 6 hours following dosing |
| Reldesemtiv Maximum Observed Plasma Concentration (Cmax) | End of Week 8 | Determined by evaluation of reldesemtiv plasma concentrations from blood samples collected prior to dosing and at 1, 3, and 6 hours following dosing |
Countries
Canada, United States
Participant flow
Recruitment details
Patients with SMA were enrolled at 18 sites in Canada and the United States. The first patient was enrolled on 14 January 2016 and the last patient completed on 31 May 2018.
Pre-assignment details
Eligible patients were male or female, ≥12 y of age and had a genetically confirmed diagnosis of SMA. Ambulatory patients were able to walk ≥50 m in 6 min; and non-ambulatory patients were able to tolerate upright sitting with support for 3 h. Patients had an FVC \>20% predicted, an HFMS-E score ≥10 and ≤54, and elbow and knee flexion ≤90 degrees.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Patients randomized to this treatment arm received a placebo suspension twice daily for 8 weeks. | 26 |
| Reldesemtiv 150 mg Twice Daily Patient randomized to this treatment arm received reldesemtiv suspension at a dose of 150 mg, twice daily for 8 weeks. | 24 |
| Reldesemtiv 450 mg Twice Daily Patients randomized to this treatment arm received reldesemtiv suspension at a dose of 450 mg, twice daily for 8 weeks. | 20 |
| Total | 70 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 | 1 |
| Overall Study | Protocol Violation | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo | Reldesemtiv 150 mg Twice Daily | Reldesemtiv 450 mg Twice Daily | Total |
|---|---|---|---|---|
| Age, Continuous | 28.5 years STANDARD_DEVIATION 16.03 | 27.8 years STANDARD_DEVIATION 11.96 | 32.6 years STANDARD_DEVIATION 17.92 | 29.4 years STANDARD_DEVIATION 15.27 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 1 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 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 |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 22 Participants | 23 Participants | 18 Participants | 63 Participants |
| Sex: Female, Male Female | 11 Participants | 10 Participants | 8 Participants | 29 Participants |
| Sex: Female, Male Male | 15 Participants | 14 Participants | 12 Participants | 41 Participants |
| Time since genetically confirmed diagnosis | 139.2 months STANDARD_DEVIATION 75.09 | 138.8 months STANDARD_DEVIATION 81.45 | 101.4 months STANDARD_DEVIATION 82.27 | 128.2 months STANDARD_DEVIATION 80.06 |
| Time since SMA symptom onset | 302.5 months STANDARD_DEVIATION 170.11 | 246.8 months STANDARD_DEVIATION 105.93 | 299.8 months STANDARD_DEVIATION 174.32 | 282.6 months STANDARD_DEVIATION 152.56 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 26 | 0 / 24 | 0 / 20 |
| other Total, other adverse events | 24 / 26 | 20 / 24 | 17 / 20 |
| serious Total, serious adverse events | 0 / 26 | 2 / 24 | 2 / 20 |
Outcome results
Primary
Change From Baseline to Week 8 in Forced Vital Capacity (FVC)
FVC was measured using a calibrated spirometer (in units of liters). Patients were instructed to take as deep an inspiration as possible followed by a maximum exhalation (blowing out all the air in their lungs).
Time frame: baseline and 8 weeks
Population: The analysis population includes patients who received at least 1 dose of reldesemtiv and had results from the relevant outcome measure at Week 8.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 8 in Forced Vital Capacity (FVC) | -0.02 liters | Standard Error 0.042 |
| Reldesemtiv 150 mg Twice Daily | Change From Baseline to Week 8 in Forced Vital Capacity (FVC) | -0.03 liters | Standard Error 0.043 |
| Reldesemtiv 450 mg Twice Daily | Change From Baseline to Week 8 in Forced Vital Capacity (FVC) | -0.07 liters | Standard Error 0.05 |
p-value: 0.908695% CI: [-0.13, 0.11]Mixed Models Analysis
p-value: 0.436195% CI: [-0.18, 0.08]Mixed Models Analysis
Primary
Change From Baseline to Week 8 in Maximum Expiratory Pressure (MEP)
MEP was measured (in units of cm H20) using a calibrated spirometer with an exspiratory pressure valve attached. For the test, patients were asked to maximally inhale then perform a forced exhalation with as forcefully as possible.
Time frame: baseline and 8 weeks
Population: The analysis population includes patients who received at least 1 dose of reldesemtiv and had results from the relevant outcome measure at Week 8.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 8 in Maximum Expiratory Pressure (MEP) | -4.22 cm H2O | Standard Error 3.843 |
| Reldesemtiv 150 mg Twice Daily | Change From Baseline to Week 8 in Maximum Expiratory Pressure (MEP) | 7.47 cm H2O | Standard Error 3.941 |
| Reldesemtiv 450 mg Twice Daily | Change From Baseline to Week 8 in Maximum Expiratory Pressure (MEP) | 8.93 cm H2O | Standard Error 4.517 |
p-value: 0.037895% CI: [0.68, 22.7]Mixed Models Analysis
p-value: 0.029895% CI: [1.33, 24.97]Mixed Models Analysis
Primary
Change From Baseline to Week 8 in Maximum Inspiratory Pressure (MIP)
MIP was measured (in units of cm H20) using a calibrated spirometer with an inspiratory pressure valve attached. For the test, patients were asked to inhale as forcefully as possible, to their maximum pressure.
Time frame: baseline and 8 weeks
Population: The analysis population includes patients who received at least 1 dose of reldesemtiv and had results from the relevant outcome measure at Week 8.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 8 in Maximum Inspiratory Pressure (MIP) | -2.62 cm H2O | Standard Error 3.317 |
| Reldesemtiv 150 mg Twice Daily | Change From Baseline to Week 8 in Maximum Inspiratory Pressure (MIP) | -5.56 cm H2O | Standard Error 3.401 |
| Reldesemtiv 450 mg Twice Daily | Change From Baseline to Week 8 in Maximum Inspiratory Pressure (MIP) | -1.63 cm H2O | Standard Error 3.901 |
p-value: 0.538295% CI: [-12.43, 6.55]Mixed Models Analysis
p-value: 0.846495% CI: [-9.19, 11.18]Mixed Models Analysis
Primary
Change From Baseline to Week 8 in Revised Upper Limb Module (RULM)
The RULM assessed motor function in the upper limbs (specifically shoulder, elbow, wrist, and hand function) that related to activities of everyday life. The RULM consisted of 20 items, 1 of which was scored on a 7-point scale (from 0 to 6), 18 were scored on a 3-point scale (from 0 to 2), and 1 was scored on a 2-point scale (0 or 1). The total score was the sum of each response and could range from a minimum of 0 to a maximum of 43 points. Higher scores reflected better motor function.
Time frame: baseline and 8 weeks
Population: The analysis population includes patients who received at least 1 dose of reldesemtiv and had results from the relevant outcome measure at Week 8.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 8 in Revised Upper Limb Module (RULM) | 0.54 score on a scale | Standard Error 0.397 |
| Reldesemtiv 150 mg Twice Daily | Change From Baseline to Week 8 in Revised Upper Limb Module (RULM) | 1.15 score on a scale | Standard Error 0.406 |
| Reldesemtiv 450 mg Twice Daily | Change From Baseline to Week 8 in Revised Upper Limb Module (RULM) | 0.43 score on a scale | Standard Error 0.468 |
p-value: 0.287895% CI: [-0.53, 1.75]Mixed Models Analysis
p-value: 0.851295% CI: [-1.34, 1.11]Mixed Models Analysis
Primary
Change From Baseline to Week 8 in the 6MWT
The 6MWT measured the distance (in meters) a patient walked in 6 minutes.
Time frame: baseline and 8 weeks
Population: This test was evaluated in ambulatory patients only.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 8 in the 6MWT | 1.39 meters | Standard Error 7.692 |
| Reldesemtiv 150 mg Twice Daily | Change From Baseline to Week 8 in the 6MWT | 9.11 meters | Standard Error 6.826 |
| Reldesemtiv 450 mg Twice Daily | Change From Baseline to Week 8 in the 6MWT | 26.28 meters | Standard Error 9.641 |
p-value: 0.468495% CI: [-13.86, 29.3]Mixed Models Analysis
p-value: 0.058495% CI: [-0.95, 50.74]Mixed Models Analysis
Primary
Change From Baseline to Week 8 in the Hammersmith Functional Motor Scale-Expanded (HFMS-E)
The HFMS-E evaluated the level of independent mobility and motor skills through assessment of 33 test-items, each scored from 0 (worse) to 2 (better). The total score was calculated as the sum of the scores among the 33 test items, and has a range from 0 to 66.
Time frame: baseline and 8 weeks
Population: The analysis population includes patients who received at least 1 dose of reldesemtiv and had results from the relevant outcome measure at Week 8.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 8 in the Hammersmith Functional Motor Scale-Expanded (HFMS-E) | 1.40 score on a scale | Standard Error 0.637 |
| Reldesemtiv 150 mg Twice Daily | Change From Baseline to Week 8 in the Hammersmith Functional Motor Scale-Expanded (HFMS-E) | 1.02 score on a scale | Standard Error 0.675 |
| Reldesemtiv 450 mg Twice Daily | Change From Baseline to Week 8 in the Hammersmith Functional Motor Scale-Expanded (HFMS-E) | 0.39 score on a scale | Standard Error 0.748 |
p-value: 0.684995% CI: [-2.23, 1.48]Mixed Models Analysis
p-value: 0.309195% CI: [-2.96, 0.95]Mixed Models Analysis
Primary
Change From Baseline to Week 8 in the TUG Test
The TUG test measured the time (in seconds) it took for a patient to rise from a chair, walk 3 meters, turn around, walk back to the chair and sit down.
Time frame: baseline and 8 weeks
Population: This test was evaluated in ambulatory patients only.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 8 in the TUG Test | 0.24 seconds | Standard Error 1.837 |
| Reldesemtiv 150 mg Twice Daily | Change From Baseline to Week 8 in the TUG Test | -0.54 seconds | Standard Error 1.708 |
| Reldesemtiv 450 mg Twice Daily | Change From Baseline to Week 8 in the TUG Test | -2.87 seconds | Standard Error 2.675 |
p-value: 0.761295% CI: [-6.08, 4.52]Mixed Models Analysis
p-value: 0.350295% CI: [-9.91, 3.7]Mixed Models Analysis
Primary
Investigator Global Assessment at the End of Week 8
The Investigator assessed whether patient appeared the same, better, or worse than prior to dosing on Day 1.
Time frame: 8 weeks
Population: The analysis population includes patients who received at least 1 dose of reldesemtiv and had results from the relevant outcome measure at Week 8.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Investigator Global Assessment at the End of Week 8 | Same as pre-dose | 18 Participants |
| Placebo | Investigator Global Assessment at the End of Week 8 | Better than pre-dose | 6 Participants |
| Placebo | Investigator Global Assessment at the End of Week 8 | Worse than pre-dose | 0 Participants |
| Reldesemtiv 150 mg Twice Daily | Investigator Global Assessment at the End of Week 8 | Same as pre-dose | 17 Participants |
| Reldesemtiv 150 mg Twice Daily | Investigator Global Assessment at the End of Week 8 | Better than pre-dose | 7 Participants |
| Reldesemtiv 150 mg Twice Daily | Investigator Global Assessment at the End of Week 8 | Worse than pre-dose | 0 Participants |
| Reldesemtiv 450 mg Twice Daily | Investigator Global Assessment at the End of Week 8 | Better than pre-dose | 6 Participants |
| Reldesemtiv 450 mg Twice Daily | Investigator Global Assessment at the End of Week 8 | Worse than pre-dose | 0 Participants |
| Reldesemtiv 450 mg Twice Daily | Investigator Global Assessment at the End of Week 8 | Same as pre-dose | 11 Participants |
Comparison: Odds ratio of active vs placebo comparison of the patients' global assessment of better than pre-dose vs same or worse than pre-dosep-value: 0.765595% CI: [0.34, 4.4]Regression, Logistic
Comparison: Odds ratio of active vs placebo comparison of the patients' global assessment of better than pre-dose vs same or worse than pre-dosep-value: 0.49295% CI: [0.41, 6.25]Regression, Logistic
Primary
Muscle Strength Mega-Score at Week 8
Muscle strength of 3 muscle groups (elbow flexion, knee extension, and shoulder abduction) were measured bilaterally using a hand-held dynamometer. Muscle strength was measured twice for each body location; if the variability between the 2 measures was \> 15%, a third measure was obtained. The maximum muscle strength of the 2 measurements was identified and transformed as a percent change from baseline using the equation: (\[postbaseline value - baseline value\] / baseline value) × 100. The mega-score was a composite score that averaged strength across the 3 muscle groups. It was calculated as the mean of the non-missing transformed muscle strength scores among the 3 muscle groups each measure bilaterally (totaling 6 body locations).
Time frame: baseline and 8 weeks
Population: The analysis population includes patients who received at least 1 dose of reldesemtiv and had results from the relevant outcome measure at Week 8.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Muscle Strength Mega-Score at Week 8 | 14.34 percent change | Standard Error 5.298 |
| Reldesemtiv 150 mg Twice Daily | Muscle Strength Mega-Score at Week 8 | 9.76 percent change | Standard Error 5.393 |
| Reldesemtiv 450 mg Twice Daily | Muscle Strength Mega-Score at Week 8 | -0.88 percent change | Standard Error 6.247 |
p-value: 0.546195% CI: [-19.69, 10.52]Mixed Models Analysis
p-value: 0.067295% CI: [-31.56, 1.11]Mixed Models Analysis
Primary
Patient Global Assessment at the End of Week 8
Patients assessed whether they felt the same, better, or worse than prior to dosing on Day 1.
Time frame: 8 weeks
Population: The analysis population includes patients who received at least 1 dose of reldesemtiv and had results from the relevant outcome measure at Week 8.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Patient Global Assessment at the End of Week 8 | Same as pre-dose | 13 Participants |
| Placebo | Patient Global Assessment at the End of Week 8 | Better than pre-dose | 12 Participants |
| Placebo | Patient Global Assessment at the End of Week 8 | Worse than pre-dose | 0 Participants |
| Reldesemtiv 150 mg Twice Daily | Patient Global Assessment at the End of Week 8 | Same as pre-dose | 15 Participants |
| Reldesemtiv 150 mg Twice Daily | Patient Global Assessment at the End of Week 8 | Better than pre-dose | 7 Participants |
| Reldesemtiv 150 mg Twice Daily | Patient Global Assessment at the End of Week 8 | Worse than pre-dose | 2 Participants |
| Reldesemtiv 450 mg Twice Daily | Patient Global Assessment at the End of Week 8 | Better than pre-dose | 7 Participants |
| Reldesemtiv 450 mg Twice Daily | Patient Global Assessment at the End of Week 8 | Worse than pre-dose | 0 Participants |
| Reldesemtiv 450 mg Twice Daily | Patient Global Assessment at the End of Week 8 | Same as pre-dose | 11 Participants |
Comparison: Odds ratio of active vs placebo comparison of the patients' global assessment of better than pre-dose vs same or worse than pre-dosep-value: 0.168695% CI: [0.13, 1.43]Regression, Logistic
Comparison: Odds ratio of active vs placebo comparison of the patients' global assessment of better than pre-dose vs same or worse than pre-dosep-value: 0.525995% CI: [0.2, 2.3]Regression, Logistic
Secondary
Reldesemtiv Area Under the Plasma Concentration-time Curve From 0 to 12 Hours (AUC0-12)
Determined by evaluation of reldesemtiv plasma concentrations from blood samples collected prior to dosing and at 1, 3, and 6 hours following dosing
Time frame: End of Week 8
Population: The analysis population includes patients who had an evaluable reldesemtiv AUC0-12 value at Week 8.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Reldesemtiv Area Under the Plasma Concentration-time Curve From 0 to 12 Hours (AUC0-12) | 9.0 hour x microgram/milliliter | Geometric Coefficient of Variation 49.38 |
| Reldesemtiv 150 mg Twice Daily | Reldesemtiv Area Under the Plasma Concentration-time Curve From 0 to 12 Hours (AUC0-12) | 25.0 hour x microgram/milliliter | Geometric Coefficient of Variation 52.19 |
Secondary
Reldesemtiv Maximum Observed Plasma Concentration (Cmax)
Determined by evaluation of reldesemtiv plasma concentrations from blood samples collected prior to dosing and at 1, 3, and 6 hours following dosing
Time frame: End of Week 8
Population: The analysis population includes all patients who had an evaluable reldesemtiv Cmax value at Week 8.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Reldesemtiv Maximum Observed Plasma Concentration (Cmax) | 1.40 microgram/milliliter | Geometric Coefficient of Variation 43.18 |
| Reldesemtiv 150 mg Twice Daily | Reldesemtiv Maximum Observed Plasma Concentration (Cmax) | 3.34 microgram/milliliter | Geometric Coefficient of Variation 48.77 |