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Study of Safety, Tolerability & Efficacy of CK-2017357 in Amyotrophic Lateral Sclerosis (ALS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01709149
Recruitment Status : Completed
First Posted : October 18, 2012
Results First Posted : March 31, 2020
Last Update Posted : March 31, 2020
Sponsor:
Information provided by (Responsible Party):
Cytokinetics

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Amyotrophic Lateral Sclerosis
Interventions Drug: CK-2017357
Other: Placebo tablets
Drug: Riluzole
Enrollment 711
Recruitment Details Patients with familial or sporadic amyotrophic lateral sclerosis were enrolled at 73 sites in Canada, France, Germany, Ireland, Netherlands, Spain, the United Kingdom, and the United States. The first patient was screened on 23 October 2012 and the last subject completed follow-up on 21 March 2014.
Pre-assignment Details A total of 711 patients were enrolled in the study and began treatment with open-label tirasemtiv during the 7-day lead-in phase of the study. Patients who completed this phase were randomized (1:1) to receive either placebo (N=295) or tirasemtiv (N=301) in the double-blind treatment period.
Arm/Group Title Open-label lead-in Treatment: Tirasemtiv Double-blind Treatment: Placebo Double-blind Treatment: Tirasemtiv
Hide Arm/Group Description Tirasemtiv 125 mg oral capsules administered twice daily for 7 days prior to randomization to the Double-blind treatment period. Placebo oral capsules administered twice daily for a total of 12 weeks of double-blind dosing. Tirasemtiv 125 mg oral capsules administered twice daily. Minimum dose was 125 mg bid and patients were up- or down-titrated over 3 to 4 weeks to the patient's maximum tolerated dose (MTD) to a maximum of 250 mg twice daily. Patients then remained at their MTD for an additional 9 weeks, for a total of 12 weeks of double-blind dosing.
Period Title: Open-label Lead-in Phase
Started 711 0 0
Completed 596 0 0
Not Completed 115 0 0
Reason Not Completed
Adverse Event             109             0             0
Withdrawal by Subject             2             0             0
Death             1             0             0
Protocol Violation             3             0             0
Period Title: Double-blind, Placebo-controlled Phase
Started 0 295 301
Completed 0 269 204
Not Completed 0 26 97
Reason Not Completed
Adverse Event             0             12             78
Withdrawal by Subject             0             7             12
Physician Decision             0             2             5
Death             0             2             0
not defined             0             1             2
Lost to Follow-up             0             2             0
Arm/Group Title Did Not Complete Open-label Lead-in Treatment Double-blind Treatment: Placebo Double-blind Treatment: Tirasemtiv Total
Hide Arm/Group Description Tirasemtiv 125 mg oral capsules administered twice daily for 7 days. This group started open-label treatment but discontinued early and did not receive double-blind treatment. Placebo oral capsules administered twice daily for a total of 12 weeks of double-blind dosing. Tirasemtiv 125 mg oral capsules administered twice daily, which was up- or down-titrated over 3 to 4 weeks to the patient's maximum tolerated dose (MTD) to a maximum of 250 mg twice daily. Patients then remained at their MTD for an additional 9 weeks, for a total of 12 weeks of double-blind dosing. Total of all reporting groups
Overall Number of Baseline Participants 115 295 301 711
Hide Baseline Analysis Population Description
Safety Analysis Set (all patients who received any study drug)
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 115 participants 295 participants 301 participants 711 participants
60.0  (9.83) 56.9  (11.10) 57.0  (11.17) 57.5  (10.98)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 115 participants 295 participants 301 participants 711 participants
Female
52
  45.2%
88
  29.8%
86
  28.6%
226
  31.8%
Male
63
  54.8%
207
  70.2%
215
  71.4%
485
  68.2%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 115 participants 295 participants 301 participants 711 participants
American Indian or Alaska Native
0
   0.0%
1
   0.3%
0
   0.0%
1
   0.1%
Asian
2
   1.7%
2
   0.7%
6
   2.0%
10
   1.4%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
1
   0.3%
1
   0.1%
Black or African American
3
   2.6%
8
   2.7%
9
   3.0%
20
   2.8%
White
102
  88.7%
250
  84.7%
259
  86.0%
611
  85.9%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
8
   7.0%
34
  11.5%
26
   8.6%
68
   9.6%
Time since ALS symptom onset  
Median (Full Range)
Unit of measure:  Months
Number Analyzed 115 participants 295 participants 301 participants 711 participants
24.0
(4 to 278)
21.0
(4 to 224)
23.0
(5 to 272)
22.0
(4 to 278)
Site of symptom onset  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 115 participants 295 participants 301 participants 711 participants
Lower limb
43
  37.4%
110
  37.3%
116
  38.5%
269
  37.8%
Upper limb
51
  44.3%
145
  49.2%
149
  49.5%
345
  48.5%
Bulbar
20
  17.4%
40
  13.6%
35
  11.6%
95
  13.4%
Respiratory
1
   0.9%
0
   0.0%
1
   0.3%
2
   0.3%
El Escorial Diagnostic Criteria for ALS   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 115 participants 295 participants 301 participants 711 participants
Possible
9
   7.8%
28
   9.5%
31
  10.3%
68
   9.6%
Probable, laboratory supported
15
  13.0%
57
  19.3%
63
  20.9%
135
  19.0%
Probable
46
  40.0%
119
  40.3%
103
  34.2%
268
  37.7%
Definite
45
  39.1%
91
  30.8%
104
  34.6%
240
  33.8%
[1]
Measure Description:

Per El Escorial criteria, ALS was diagnosed as: Possible (upper motor neuron [UMN] and lower motor neuron [LMN] signs in 1 region, or UMN signs in at least 2 regions, or UMN and LMN signs in 2 regions with no UMN signs rostral to LMN signs); Probable, Laboratory Supported (UMN signs in 1 or more regions and LMN signs defined by electromyography in at least 2 regions); Probable (UMN and LMN signs in 2 regions with some UMN signs rostral to the LMN signs); and Definite (UMN and LMN signs in 3 regions).

The El Escorial criteria do not relate to grading of ALS nor to outcome.

1.Primary Outcome
Title The Change From Baseline in ALS Functional Rating Scale-Revised (ALSFRS-R) Total Score to the Average of Values Obtained at the End of Weeks 8 and 12 of Double-blind Treatment
Hide Description The ALSFRS-R is used to measure the progression and severity of disease; it consists of 12 questions, assessing a patient's capability and independence in functional activities relevant to ALS, categorized in 4 domains: gross motor tasks, fine motor tasks, bulbar functions, and respiratory function. Each question is scored from 0 (indicating incapable or dependent) to 4 (normal). The total score ranges from 0 to 48, with higher scores reflecting more normal function and lower scores reflecting more impaired function.
Time Frame Baseline, 8 weeks, 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Modified Full Analysis Set
Arm/Group Title Placebo Tirasemtiv
Hide Arm/Group Description:
Placebo oral capsules administered twice daily for a total of 12 weeks of double-blind dosing.
Tirasemtiv 125 mg oral capsules administered twice daily, which was up- or down-titrated over 3 to 4 weeks to the patient's maximum tolerated dose (MTD) to a maximum of 250 mg twice daily. Patients then remained at their MTD for an additional 9 weeks, for a total of 12 weeks of double-blind dosing.
Overall Number of Participants Analyzed 210 178
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-2.40  (0.246) -2.98  (0.277)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Tirasemtiv
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1140
Comments [Not Specified]
Method Repeated-measures mixed model
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -0.58
Confidence Interval (2-Sided) 95%
-1.30 to 0.14
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.366
Estimation Comments Least squares mean difference: tirasemtiv minus placebo
2.Secondary Outcome
Title Change From Baseline in Maximum Voluntary Ventilation (MVV) to the Average of Values Obtained at the End of Weeks 8 and 12 of Double-blind Treatment
Hide Description MVV was measured as the volume (in liters) of air that could be exhaled during 12 seconds of rapid deep breathing; for analysis purposes, the measured volume was extrapolated to 1 minute (to give units of L/min).
Time Frame Baseline, 8 weeks, 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Modified Full Analysis Set
Arm/Group Title Placebo Tirasemtiv
Hide Arm/Group Description:
Placebo oral capsules administered twice daily for a total of 12 weeks of double-blind dosing.
Tirasemtiv 125 mg oral capsules administered twice daily, which was up- or down-titrated over 3 to 4 weeks to the patient's maximum tolerated dose (MTD) to a maximum of 250 mg twice daily. Patients then remained at their MTD for an additional 9 weeks, for a total of 12 weeks of double-blind dosing.
Overall Number of Participants Analyzed 210 178
Least Squares Mean (Standard Error)
Unit of Measure: L/min
-4.27  (1.332) -3.79  (1.497)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Tirasemtiv
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8083
Comments [Not Specified]
Method Repeated-measures mixed model
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value 0.48
Confidence Interval (2-Sided) 95%
-3.38 to 4.34
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.963
Estimation Comments Least squares mean difference: tirasemtiv minus placebo
3.Secondary Outcome
Title Change From Baseline in Sniff Nasal Inspiratory Pressure (SNIP) to the Average of Values Obtained at the End of Weeks 8 and 12 of Double-blind Treatment
Hide Description SNIP was measured at functional residual capacity, the bottom of the tidal breathing cycle, through 1 plugged nostril while the other remained open. Inspiratory pressure is a negative number where a larger negative number represents . . . A forceful, maximal inspiratory sniff was performed and a peak pressure value reported. The best result (ie, the highest number) from 5 tests was recorded as the SNIP.
Time Frame Baseline, 8 weeks, 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Modified Full Analysis Set
Arm/Group Title Placebo Tirasemtiv
Hide Arm/Group Description:
Placebo oral capsules administered twice daily for a total of 12 weeks of double-blind dosing.
Tirasemtiv 125 mg oral capsules administered twice daily, which was up- or down-titrated over 3 to 4 weeks to the patient's maximum tolerated dose (MTD) to a maximum of 250 mg twice daily. Patients then remained at their MTD for an additional 9 weeks, for a total of 12 weeks of double-blind dosing.
Overall Number of Participants Analyzed 210 178
Least Squares Mean (Standard Error)
Unit of Measure: cm H2O
-0.89  (1.103) -4.29  (1.243)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Tirasemtiv
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0372
Comments [Not Specified]
Method Repeated-measures mixed model
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -3.40
Confidence Interval (2-Sided) 95%
-6.60 to -0.20
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.627
Estimation Comments Least squares mean difference: tirasemtiv minus placebo
4.Secondary Outcome
Title Change From Baseline in Slow Vital Capacity (SVC) to the Average of Values Obtained at the End of Weeks 8 and 12 of Double-blind Treatment
Hide Description SVC was measured using a spirometer (in units of liters). Following 3 to 5 breaths at rest, the patients were instructed to take as deep an inspiration as possible followed by a maximum exhalation (blowing out all the air in their lungs). Values obtained were converted to % predicted values (ie, the test result as a percent of predicted values for the patients of similar demographic and baseline characteristics [eg, height, age, sex]).
Time Frame Baseline, 8 weeks, 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Modified Full Analysis Set
Arm/Group Title Placebo Tirasemtiv
Hide Arm/Group Description:
Placebo oral capsules administered twice daily for a total of 12 weeks of double-blind dosing.
Tirasemtiv 125 mg oral capsules administered twice daily, which was up- or down-titrated over 3 to 4 weeks to the patient's maximum tolerated dose (MTD) to a maximum of 250 mg twice daily. Patients then remained at their MTD for an additional 9 weeks, for a total of 12 weeks of double-blind dosing.
Overall Number of Participants Analyzed 210 178
Least Squares Mean (Standard Error)
Unit of Measure: % predicted
-7.24  (0.691) -2.98  (0.780)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Repeated-measures mixed model
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value 4.25
Confidence Interval (2-Sided) 95%
2.23 to 6.28
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.030
Estimation Comments Least squares mean difference: tirasemtiv minus placebo
5.Secondary Outcome
Title Change From Baseline in Maximum Handgrip Strength in the Weaker Hand to the Average of Values Obtained at the End of Weeks 8 and 12 of Double-blind Treatment
Hide Description Maximum handgrip strength was measured using an electronic hand dynamometer; patients were asked to squeeze the device with the maximum possible force.
Time Frame Baseline, 8 weeks, 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo Tirasemtiv
Hide Arm/Group Description:
Placebo oral capsules administered twice daily for a total of 12 weeks of double-blind dosing.
Tirasemtiv 125 mg oral capsules administered twice daily, which was up- or down-titrated over 3 to 4 weeks to the patient's maximum tolerated dose (MTD) to a maximum of 250 mg twice daily. Patients then remained at their MTD for an additional 9 weeks, for a total of 12 weeks of double-blind dosing.
Overall Number of Participants Analyzed 210 178
Least Squares Mean (Standard Error)
Unit of Measure: pounds
-3.54  (0.640) -2.78  (0.714)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Tirasemtiv
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4328
Comments [Not Specified]
Method Repeated-measures mixed model
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value 0.75
Confidence Interval (2-Sided) 95%
-1.13 to 2.63
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.956
Estimation Comments Least squares mean difference: tirasemtiv minus placebo
6.Secondary Outcome
Title Change From Baseline in Handgrip Fatigability (at 60% of Target in the Weaker Hand) to the Average of Values Obtained at the End of Weeks 8 and 12 of Double-blind Treatment
Hide Description Handgrip fatigability was measured immediately following determination of maximum handgrip strength (via an electronic hand dynamometer). Once maximum handgrip strength was achieved, the force of the grip was timed for 2 minutes or until the grip strength had dropped to 60% of the maximum, whichever came first.
Time Frame Baseline, 8 weeks, 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Modified Full Analysis Set
Arm/Group Title Placebo Tirasemtiv
Hide Arm/Group Description:
Placebo oral capsules administered twice daily for a total of 12 weeks of double-blind dosing.
Tirasemtiv 125 mg oral capsules administered twice daily, which was up- or down-titrated over 3 to 4 weeks to the patient's maximum tolerated dose (MTD) to a maximum of 250 mg twice daily. Patients then remained at their MTD for an additional 9 weeks, for a total of 12 weeks of double-blind dosing.
Overall Number of Participants Analyzed 210 178
Least Squares Mean (Standard Error)
Unit of Measure: seconds
1.76  (2.863) 2.01  (3.331)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Tirasemtiv
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9546
Comments [Not Specified]
Method Repeated-measures mixed model
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value 0.25
Confidence Interval (2-Sided) 95%
-8.40 to 8.90
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.399
Estimation Comments Least squares mean difference: tirasemtiv minus placebo
7.Secondary Outcome
Title Change From Baseline in Muscle Strength Mega-Score Based on Percent Change in Muscle Strength Measurements to the Average at the End of Weeks 8 and 12 of Double-blind Treatment
Hide Description A hand-held dynamometer (HHD), with a scale of 0 to 300 pounds, was used to measure muscle strength and handgrip strength (bilateral); the muscle groups tested were: elbow flexion (bilateral), wrist extension (bilateral), knee extension (bilateral), and ankle dorsiflexion (bilateral). For each assessment time point, the percent change from baseline was calculated for each muscle group and handgrip strength. The muscle strength mega-score was calculated as the average of the changes (ie, percent change from baseline) observed for each muscle groups as well as handgrip strength. For this endpoint, negative values indicate a decline in muscle strength.
Time Frame Baseline, 8 weeks, 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo Tirasemtiv
Hide Arm/Group Description:
Placebo oral capsules administered twice daily for a total of 12 weeks of double-blind dosing.
Tirasemtiv 125 mg oral capsules administered twice daily, which was up- or down-titrated over 3 to 4 weeks to the patient's maximum tolerated dose (MTD) to a maximum of 250 mg twice daily. Patients then remained at their MTD for an additional 9 weeks, for a total of 12 weeks of double-blind dosing.
Overall Number of Participants Analyzed 210 178
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-10.71  (2.108) -9.10  (2.425)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Tirasemtiv
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6166
Comments [Not Specified]
Method Repeated-measures mixed model
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value 1.61
Confidence Interval (2-Sided) 95%
-4.70 to 7.91
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.207
Estimation Comments Least squares mean difference: tirasemtiv minus placebo
Time Frame AEs were collected from the first dose of open-label study drug through 30 days after the last dose of study drug or Week 16, whichever was earlier.
Adverse Event Reporting Description An AE was treatment-emergent if it started or worsened in severity after the first dose of study drug (in either the open-label or double-blind periods). For the double-blind period, if the AE started in the open-label period and continued into the double-blind period for more than 96 hours, it was assigned an onset of 96 hours after the first dose of double-blind study drug.
 
Arm/Group Title Open-label lead-in Treatment: Tirasemtiv Double-blind Treatment: Placebo Double-blind Treatment: Tirasemtiv
Hide Arm/Group Description Tirasemtiv 125 mg oral capsules administered twice daily for 7 days prior to randomization to the Double-blind treatment period. Placebo oral capsules administered twice daily for a total of 12 weeks of double-blind dosing. Tirasemtiv 125 mg oral capsules administered twice daily, which was up- or down-titrated over 3 to 4 weeks to the patient's maximum tolerated dose (MTD) to a maximum of 250 mg twice daily. Patients then remained at their MTD for an additional 9 weeks, for a total of 12 weeks of double-blind dosing.
All-Cause Mortality
Open-label lead-in Treatment: Tirasemtiv Double-blind Treatment: Placebo Double-blind Treatment: Tirasemtiv
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/711 (0.28%)   3/295 (1.02%)   2/301 (0.66%) 
Hide Serious Adverse Events
Open-label lead-in Treatment: Tirasemtiv Double-blind Treatment: Placebo Double-blind Treatment: Tirasemtiv
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   13/711 (1.83%)   16/295 (5.42%)   27/301 (8.97%) 
Blood and lymphatic system disorders       
Coagulopathy  1  0/711 (0.00%)  0/295 (0.00%)  1/301 (0.33%) 
Cardiac disorders       
Angina pectoris  1  0/711 (0.00%)  1/295 (0.34%)  1/301 (0.33%) 
Atrial fibrillation  1  0/711 (0.00%)  1/295 (0.34%)  1/301 (0.33%) 
Myocardial infarction  1  0/711 (0.00%)  1/295 (0.34%)  1/301 (0.33%) 
Tachycardia paroxysmal  1  1/711 (0.14%)  0/295 (0.00%)  0/301 (0.00%) 
Acute coronary syndrome  1  0/711 (0.00%)  0/295 (0.00%)  1/301 (0.33%) 
Bradycardia  1  0/711 (0.00%)  0/295 (0.00%)  1/301 (0.33%) 
Gastrointestinal disorders       
Dysphagia  1  0/711 (0.00%)  1/295 (0.34%)  2/301 (0.66%) 
Abdominal pain upper  1  0/711 (0.00%)  1/295 (0.34%)  0/301 (0.00%) 
Faeces discoloured  1  0/711 (0.00%)  1/295 (0.34%)  0/301 (0.00%) 
Infections and infestations       
Pneumonia  1  1/711 (0.14%)  1/295 (0.34%)  2/301 (0.66%) 
Kidney infection  1  0/711 (0.00%)  0/295 (0.00%)  1/301 (0.33%) 
Parainfluenzae virus infection  1  0/711 (0.00%)  1/295 (0.34%)  0/301 (0.00%) 
Post procedural infection  1  0/711 (0.00%)  1/295 (0.34%)  0/301 (0.00%) 
Respiratory tract infection  1  0/711 (0.00%)  1/295 (0.34%)  0/301 (0.00%) 
Injury, poisoning and procedural complications       
Humerus fracture  1  1/711 (0.14%)  0/295 (0.00%)  0/301 (0.00%) 
Joint dislocation  1  1/711 (0.14%)  0/295 (0.00%)  0/301 (0.00%) 
Face injury  1  0/711 (0.00%)  1/295 (0.34%)  0/301 (0.00%) 
Musculoskeletal and connective tissue disorders       
Spinal column stenosis  1  0/711 (0.00%)  0/295 (0.00%)  1/301 (0.33%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Lung neoplasm malignant  1  1/711 (0.14%)  0/295 (0.00%)  0/301 (0.00%) 
Prostate cancer  1  0/711 (0.00%)  0/295 (0.00%)  1/301 (0.33%) 
Nervous system disorders       
cerebral haemorrhage  1  1/711 (0.14%)  0/295 (0.00%)  0/301 (0.00%) 
Cerebrovascular accident  1  0/711 (0.00%)  0/295 (0.00%)  1/301 (0.33%) 
Dysarthria  1  0/711 (0.00%)  0/295 (0.00%)  1/301 (0.33%) 
Paresis  1  0/711 (0.00%)  0/295 (0.00%)  1/301 (0.33%) 
Spinal haematoma  1  0/711 (0.00%)  0/295 (0.00%)  1/301 (0.33%) 
Tremor  1  0/711 (0.00%)  0/295 (0.00%)  1/301 (0.33%) 
Psychiatric disorders       
Confusional state  1  2/711 (0.28%)  0/295 (0.00%)  2/301 (0.66%) 
Depression  1  2/711 (0.28%)  0/295 (0.00%)  0/301 (0.00%) 
Delirium  1  0/711 (0.00%)  0/295 (0.00%)  2/301 (0.66%) 
Agitation  1  0/711 (0.00%)  0/295 (0.00%)  1/301 (0.33%) 
Suicidal ideation  1  0/711 (0.00%)  0/295 (0.00%)  1/301 (0.33%) 
Renal and urinary disorders       
Urinary retention  1  0/711 (0.00%)  1/295 (0.34%)  0/301 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Pulmonary embolism  1  2/711 (0.28%)  1/295 (0.34%)  1/301 (0.33%) 
Respiratory failure  1  0/711 (0.00%)  3/295 (1.02%)  1/301 (0.33%) 
Pneumonia aspiration  1  1/711 (0.14%)  1/295 (0.34%)  1/301 (0.33%) 
Hypercapnia  1  1/711 (0.14%)  1/295 (0.34%)  0/301 (0.00%) 
Acute respiratory failure  1  0/711 (0.00%)  0/295 (0.00%)  1/301 (0.33%) 
Vascular disorders       
Deep vein thrombosis  1  0/711 (0.00%)  1/295 (0.34%)  1/301 (0.33%) 
1
Term from vocabulary, MedDRA (15.1)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Open-label lead-in Treatment: Tirasemtiv Double-blind Treatment: Placebo Double-blind Treatment: Tirasemtiv
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   525/711 (73.84%)   258/295 (87.46%)   291/301 (96.68%) 
Gastrointestinal disorders       
Nausea  1  77/711 (10.83%)  23/295 (7.80%)  66/301 (21.93%) 
Diarrhoea  1  10/711 (1.41%)  17/295 (5.76%)  22/301 (7.31%) 
Constipation  1  11/711 (1.55%)  17/295 (5.76%)  19/301 (6.31%) 
Dysphagia  1  6/711 (0.84%)  10/295 (3.39%)  16/301 (5.32%) 
General disorders       
Fatigue  1  111/711 (15.61%)  42/295 (14.24%)  100/301 (33.22%) 
Asthenia  1  40/711 (5.63%)  37/295 (12.54%)  48/301 (15.95%) 
Oedema peripheral  1  5/711 (0.70%)  17/295 (5.76%)  18/301 (5.98%) 
Infections and infestations       
Nasopharyngitis  1  7/711 (0.98%)  19/295 (6.44%)  19/301 (6.31%) 
Urinary tract infection  1  5/711 (0.70%)  14/295 (4.75%)  17/301 (5.65%) 
Upper respiratory tract infection  1  3/711 (0.42%)  15/295 (5.08%)  9/301 (2.99%) 
Injury, poisoning and procedural complications       
Contusion  1  6/711 (0.84%)  25/295 (8.47%)  22/301 (7.31%) 
Laceration  1  6/711 (0.84%)  11/295 (3.73%)  18/301 (5.98%) 
Excoriation  1  2/711 (0.28%)  15/295 (5.08%)  17/301 (5.65%) 
Metabolism and nutrition disorders       
Decreased appetite  1  23/711 (3.23%)  9/295 (3.05%)  30/301 (9.97%) 
Musculoskeletal and connective tissue disorders       
Muscle spasms  1  30/711 (4.22%)  16/295 (5.42%)  45/301 (14.95%) 
Muscular weakness  1  21/711 (2.95%)  20/295 (6.78%)  34/301 (11.30%) 
Back pain  1  9/711 (1.27%)  20/295 (6.78%)  15/301 (4.98%) 
Pain in extremity  1  8/711 (1.13%)  17/295 (5.76%)  14/301 (4.65%) 
Musculoskeletal pain  1  6/711 (0.84%)  17/295 (5.76%)  9/301 (2.99%) 
Nervous system disorders       
Dizziness  1  291/711 (40.93%)  58/295 (19.66%)  153/301 (50.83%) 
Headache  1  30/711 (4.22%)  33/295 (11.19%)  54/301 (17.94%) 
Somnolence  1  50/711 (7.03%)  11/295 (3.73%)  39/301 (12.96%) 
Dysarthria  1  13/711 (1.83%)  7/295 (2.37%)  23/301 (7.64%) 
Tremor  1  8/711 (1.13%)  7/295 (2.37%)  17/301 (5.65%) 
Muscle contractions involuntary  1  15/711 (2.11%)  8/295 (2.71%)  16/301 (5.32%) 
Balance disorder  1  10/711 (1.41%)  3/295 (1.02%)  15/301 (4.98%) 
Psychiatric disorders       
Confusional state  1  18/711 (2.53%)  3/295 (1.02%)  33/301 (10.96%) 
Insomnia  1  16/711 (2.25%)  12/295 (4.07%)  31/301 (10.30%) 
Anxiety  1  15/711 (2.11%)  13/295 (4.41%)  20/301 (6.64%) 
Depression  1  8/711 (1.13%)  10/295 (3.39%)  16/301 (5.32%) 
Respiratory, thoracic and mediastinal disorders       
Dyspnoea  1  11/711 (1.55%)  8/295 (2.71%)  25/301 (8.31%) 
Respiratory failure  1  1/711 (0.14%)  17/295 (5.76%)  19/301 (6.31%) 
Cough  1  6/711 (0.84%)  12/295 (4.07%)  15/301 (4.98%) 
Skin and subcutaneous tissue disorders       
Rash  1  3/711 (0.42%)  3/295 (1.02%)  17/301 (5.65%) 
1
Term from vocabulary, MedDRA (15.1)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: MD Cytokinetics
Organization: Cytokinetics, Inc.
Phone: 650-624-2929
EMail: medicalaffairs@cytokinetics.com
Layout table for additonal information
Responsible Party: Cytokinetics
ClinicalTrials.gov Identifier: NCT01709149    
Other Study ID Numbers: CY 4026
First Submitted: October 16, 2012
First Posted: October 18, 2012
Results First Submitted: January 30, 2020
Results First Posted: March 31, 2020
Last Update Posted: March 31, 2020