A Study to Evaluate Efficacy, Safety and Tolerability of CK-2127107 in Patients With Amyotrophic Lateral Sclerosis (ALS) (FORTITUDE-ALS)

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ClinicalTrials.gov Identifier: NCT03160898

Recruitment Status : Completed

First Posted : May 19, 2017

Results First Posted : September 11, 2020

Last Update Posted : September 11, 2020

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Sponsor:

Collaborator:

Astellas Pharma Inc

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: Reldesemtiv Drug: Placebo
Enrollment	458

Participant Flow

Recruitment Details	Patients with familial or sporadic ALS were enrolled at 65 sites in Australia, Canada, Ireland, Netherlands, Spain, and the United States. The first patient was screened on 16 August 2017 and the last patient completed on 07 March 2019.
Pre-assignment Details	Eligible patients were male or female, ≥18 - ≤80 years of age, with familial or sporadic ALS diagnosed for ≤24 months. At screening, patients were to have upright slow vial capacity (SVC) ≥60% of predicted; must have been able to swallow tablets, perform reproducible pulmonary function tests; have normal lab tests; and have a caregiver (if needed).


Arm/Group Title	Placebo	Reldesemtiv 150 mg Twice Daily	Reldesemtiv 300 mg Twice Daily	Reldesemtiv 450 mg Twice Daily
Arm/Group Description	Patients in this group received pla...	Patients in this group received 150...	Patients in this group received 300...	Patients in this group received 450...
Arm/Group Description	Patients in this group received placebo twice daily for 12 weeks	Patients in this group received 150 mg reldesemtiv twice daily for 12 weeks	Patients in this group received 300 mg reldesemtiv twice daily for 12 weeks	Patients in this group received 450 mg reldesemtiv twice daily for 12 weeks
Period Title: Overall Study
Started	115	113 ^[1]	113	117
Completed	95	100	97	98
Not Completed	20	13	16	19
Reason Not Completed
Adverse Event	4	8	7	10
Death	1	0	0	1
Difficulty Traveling to Clinic Visits	3	0	0	1
Lost to Follow-up	1	1	1	2
Physician Decision	1	0	0	1
Progressive Disease	4	1	2	1
Protocol Violation	1	0	2	0
Sponsor Discretion	2	0	0	0
Withdrawal by Subject	1	3	2	1
Other	2	0	2	2
[1] 1 patient withdrew consent before study drug dosing and was therefore excluded from safety analysis

Baseline Characteristics

Arm/Group Title		Placebo	Reldesemtiv 150 mg Twice Daily	Reldesemtiv 300 mg Twice Daily	Reldesemtiv 450 mg Twice Daily	Total
Arm/Group Description		Patients in this group received pla...	Patients in this group received 150...	Patients in this group received 300...	Patients in this group received 450...	Total of all reporting groups
Arm/Group Description		Patients in this group received placebo twice daily for 12 weeks	Patients in this group received 150 mg reldesemtiv twice daily for 12 weeks	Patients in this group received 300 mg reldesemtiv twice daily for 12 weeks	Patients in this group received 450 mg reldesemtiv twice daily for 12 weeks	Total of all reporting groups
Overall Number of Baseline Participants		115	112	113	117	457
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	115 participants	112 participants	113 participants	117 participants	457 participants
		59.6 (10.60)	57.1 (10.91)	57.8 (10.17)	60.1 (11.00)	58.7 (10.72)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	115 participants	112 participants	113 participants	117 participants	457 participants
	Female	47 40.9%	41 36.6%	42 37.2%	50 42.7%	180 39.4%
	Male	68 59.1%	71 63.4%	71 62.8%	67 57.3%	277 60.6%
Race (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	115 participants	112 participants	113 participants	117 participants	457 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Asian	4 3.5%	2 1.8%	7 6.2%	1 0.9%	14 3.1%
	Native Hawaiian or Other Pacific Islander	0 0.0%	1 0.9%	0 0.0%	0 0.0%	1 0.2%
	Black or African American	1 0.9%	3 2.7%	6 5.3%	0 0.0%	10 2.2%
	White	107 93.0%	103 92.0%	100 88.5%	113 96.6%	423 92.6%
	More than one race	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	3 2.6%	3 2.7%	0 0.0%	3 2.6%	9 2.0%
Region of Enrollment Measure Type: Number Unit of measure: Participants	Number Analyzed	115 participants	112 participants	113 participants	117 participants	457 participants
Canada		24	22	27	27	100
Netherlands		4	2	1	4	11
United States		72	73	71	68	284
Ireland		2	2	0	0	4
Spain		8	9	10	11	38
Australia		5	4	4	7	20
Time since ALS symptom onset Mean (Standard Deviation) Unit of measure: Months
	Number Analyzed	115 participants	112 participants	113 participants	117 participants	457 participants
		22.13 (12.375)	23.87 (27.503)	22.52 (14.635)	22.69 (18.662)	22.80 (19.080)
Site of symptom onset Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	115 participants	112 participants	113 participants	117 participants	457 participants
	Upper limb	49 42.6%	52 46.4%	56 49.6%	44 37.6%	201 44.0%
	Lower limb	44 38.3%	42 37.5%	40 35.4%	43 36.8%	169 37.0%
	Bulbar	22 19.1%	18 16.1%	17 15.0%	30 25.6%	87 19.0%

Outcome Measures

1.Primary Outcome


Title	Change From Baseline to Week 12 in the Percent Predicted Slow Vital Capacity (SVC)
Description	Slow vital capacity was measured using a spirometer (in units of liter...
Description	Slow vital capacity was measured using a spirometer (in units of liters). Following 3 to 5 breaths at rest, 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 percent predicted values using the Global Lung Initiative equation (ie, the test result as a percent of predicted values for patients of similar demographic and baseline characteristics [eg, height, age, sex]).
Time Frame	Baseline to Week 12

Outcome Measure Data

Analysis Population Description

The outcome measure was analyzed for the Full Analysis Set, which consisted of all randomized patients who received any amount of study drug and had a baseline and at least 1 postbaseline efficacy assessment during double-blind treatment.


Arm/Group Title	Placebo	Reldesemtiv 150 mg Twice Daily	Reldesemtiv 300 mg Twice Daily	Reldesemtiv 450 mg Twice Daily	Reldesemtiv 300 mg & 450 mg
Arm/Group Description:	Patients in this group received pla...	Patients in this group received 150...	Patients in this group received 300...	Patients in this group received 450...	For analysis purposes, the results ...
Arm/Group Description:	Patients in this group received placebo twice daily for 12 weeks	Patients in this group received 150 mg reldesemtiv twice daily for 12 weeks	Patients in this group received 300 mg reldesemtiv twice daily for 12 weeks	Patients in this group received 450 mg reldesemtiv twice daily for 12 weeks	For analysis purposes, the results from the reldesemtiv 300 mg group and the 450 mg group were pooled.
Overall Number of Participants Analyzed	114	112	113	117	230
Least Squares Mean (Standard Error) Unit of Measure: percent predicted
	-6.46 (0.964)	-4.97 (0.952)	-4.62 (0.963)	-4.58 (0.927)	-4.60 (0.701)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Reldesemtiv 150 mg Twice Daily, Reldesemtiv 300 mg Twice Daily, Reldesemtiv 450 mg Twice Daily
	Comments	The statistical null hypothesis was as follows: there was no assumed dose-response relationship in percent predicted SVC change from baseline to Week 12 among all three active doses and placebo, expressed as: H0: -5 x µ placebo - 1 x µ 150 mg twice daily + 3 x µ 300 mg twice daily + 3 x µ 450 mg twice daily = 0 where µ was the mean of the efficacy endpoint for the designated group.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.1095
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	Analyzed by an MMRM with contrast (-5, -1, 3, 3) to reflect the assumed relationship for the 4 groups: placebo, 150, 300, and 450 mg twice daily.

Method of Estimation	Estimation Parameter	least squares mean treatment difference
	Estimated Value	1.61
	Confidence Interval	(2-Sided) 95% -0.36 to 3.58
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.003
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Reldesemtiv 150 mg Twice Daily
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.2501
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	1.49
	Confidence Interval	(2-Sided) 95% -1.05 to 4.03
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.291
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Reldesemtiv 300 mg Twice Daily
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.1549
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	1.84
	Confidence Interval	(2-Sided) 95% -0.7 to 4.38
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.29
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Reldesemtiv 450 mg Twice Daily
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.1417
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	1.88
	Confidence Interval	(2-Sided) 95% -0.63 to 4.38
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.274
	Estimation Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Reldesemtiv 300 mg & 450 mg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.0964
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	1.86
	Confidence Interval	(2-Sided) 95% -0.33 to 4.05
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.115
	Estimation Comments	[Not Specified]

2.Secondary Outcome


Title	Change From Baseline to Week 12 in the ALS Functional Rating Scale - Revised (ALSFRS-R) Total Score
Description	The ALSFRS-R is used to measure the progression and severity of disabi...
Description	The ALSFRS-R is used to measure the progression and severity of disability in patients with ALS. The ALSFRS-R consists of 12 questions, assessing a patient's capability and independence in functional activities relevant to ALS, categorized in the following 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. Higher scores reflect more normal function and lower scores reflect more impaired function.
Time Frame	Baseline to Week 12

Outcome Measure Data

Analysis Population Description


Arm/Group Title	Placebo	Reldesemtiv 150 mg Twice Daily	Reldesemtiv 300 mg Twice Daily	Reldesemtiv 450 mg Twice Daily	Reldesemtiv 300 mg & 450 mg
Arm/Group Description:	Patients in this group received pla...	Patients in this group received 150...	Patients in this group received 300...	Patients in this group received 450...	For analysis purposes, the results ...
Arm/Group Description:	Patients in this group received placebo twice daily for 12 weeks	Patients in this group received 150 mg reldesemtiv twice daily for 12 weeks	Patients in this group received 300 mg reldesemtiv twice daily for 12 weeks	Patients in this group received 450 mg reldesemtiv twice daily for 12 weeks	For analysis purposes, the results from the reldesemtiv 300 mg group and the 450 mg group were pooled.
Overall Number of Participants Analyzed	114	112	113	117	230
Least Squares Mean (Standard Error) Unit of Measure: change in score
	-3.53 (0.313)	-2.40 (0.311)	-2.62 (0.317)	-2.94 (0.307)	-2.78 (0.228)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Reldesemtiv 150 mg Twice Daily, Reldesemtiv 300 mg Twice Daily, Reldesemtiv 450 mg Twice Daily
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.0930
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	Analyzed by an MMRM with contrast (-5, -1, 3, 3) to reflect the assumed relationship for the 4 groups: placebo, 150, 300, and 450 mg twice daily.

Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	0.56
	Confidence Interval	(2-Sided) 95% -0.09 to 1.22
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.335
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Reldesemtiv 150 mg Twice Daily
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.0087
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	1.13
	Confidence Interval	(2-Sided) 95% 0.29 to 1.97
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.427
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Reldesemtiv 300 mg Twice Daily
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.0351
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	0.91
	Confidence Interval	(2-Sided) 95% 0.06 to 1.75
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.43
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Reldesemtiv 450 mg Twice Daily
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.1642
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	0.59
	Confidence Interval	(2-Sided) 95% -0.24 to 1.43
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.425
	Estimation Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Reldesemtiv 300 mg & 450 mg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.0435
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	0.75
	Confidence Interval	(2-Sided) 95% 0.02 to 1.48
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.371
	Estimation Comments	[Not Specified]

3.Secondary Outcome


Title	Slope of Muscle Strength Mega-score From Baseline to Week 12
Description	A hand-held dynamometer, with a scale of 0 to 300 pounds, was used to ...
Description	A hand-held dynamometer, 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, wrist extension, first dorsal interosseous, hip flexion, knee extension, and ankle dorsiflexion; all muscle groups were evaluated bilaterally. For each postbaseline assessment of muscle strength, the percent change from baseline was calculated for each muscle group and handgrip strength, using the following equation: ([postbaseline value - baseline value] / baseline value) × 100. The muscle-strength mega-score was calculated as the average of the changes (ie, percent change from baseline) observed for each of the muscle groups as well as handgrip strength. For this endpoint, negative values indicate a decline in muscle strength.
Time Frame	Baseline to Week 12

Outcome Measure Data

Analysis Population Description


Arm/Group Title	Placebo	Reldesemtiv 150 mg Twice Daily	Reldesemtiv 300 mg Twice Daily	Reldesemtiv 450 mg Twice Daily	Reldesemtiv 300 mg & 450 mg
Arm/Group Description:	Patients in this group received pla...	Patients in this group received 150...	Patients in this group received 300...	Patients in this group received 450...	For analysis purposes, the results ...
Arm/Group Description:	Patients in this group received placebo twice daily for 12 weeks	Patients in this group received 150 mg reldesemtiv twice daily for 12 weeks	Patients in this group received 300 mg reldesemtiv twice daily for 12 weeks	Patients in this group received 450 mg reldesemtiv twice daily for 12 weeks	For analysis purposes, the results from the reldesemtiv 300 mg group and the 450 mg group were pooled.
Overall Number of Participants Analyzed	114	112	113	117	230
Least Squares Mean (Standard Error) Unit of Measure: change in mega-score per day
	-0.1444 (0.02492)	-0.1198 (0.02463)	-0.1299 (0.02474)	-0.0956 (0.02421)	-0.1127 (0.01731)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Reldesemtiv 150 mg Twice Daily, Reldesemtiv 300 mg Twice Daily, Reldesemtiv 450 mg Twice Daily
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.3134
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	Analyzed by an MMRM with contrast (-5, -1, 3, 3) to reflect the assumed relationship for the 4 groups: placebo, 150, 300, and 450 mg twice daily.

Method of Estimation	Estimation Parameter	Slope difference
	Estimated Value	0.0276
	Confidence Interval	(2-Sided) 95% -0.0261 to 0.0813
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.02734
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Reldesemtiv 150 mg Twice Daily
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.4824
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	0.0246
	Confidence Interval	(2-Sided) 95% -0.0442 to 0.0935
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Reldesemtiv 300 mg Twice Daily
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.6787
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	0.0146
	Confidence Interval	(2-Sided) 95% -0.0544 to 0.0835
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Reldesemtiv 450 mg Twice Daily
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.1604
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	0.0488
	Confidence Interval	(2-Sided) 95% -0.0194 to 0.1171
	Estimation Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Reldesemtiv 300 mg & 450 mg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.2966
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	0.0317
	Confidence Interval	(2-Sided) 95% -0.0279 to 0.0913
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	Adverse events (AEs) were collected from administration of the first dose of study drug through 4 weeks after the last dose of study drug.
Adverse Event Reporting Description	An AE was treatment-emergent if it started or worsened (eg, increased in severity) during or after the first dose of study drug. AEs and SAEs were summarized for the Safety Analysis Set, which consisted of all randomized patients who received at least 1 dose or portion of a dose of study drug.

Arm/Group Title	Placebo		Reldesemtiv 150 mg Twice Daily		Reldesemtiv 300 mg Twice Daily		Reldesemtiv 450 mg Twice Daily
Arm/Group Description	Patients in this group received pla...		Patients in this group received 150...		Patients in this group received 300...		Patients in this group received 450...
Arm/Group Description	Patients in this group received placebo twice daily for 12 weeks		Patients in this group received 150 mg reldesemtiv twice daily for 12 weeks		Patients in this group received 300 mg reldesemtiv twice daily for 12 weeks		Patients in this group received 450 mg reldesemtiv twice daily for 12 weeks
All-Cause Mortality
	Placebo		Reldesemtiv 150 mg Twice Daily		Reldesemtiv 300 mg Twice Daily		Reldesemtiv 450 mg Twice Daily
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	2/115 (1.74%)		0/112 (0.00%)		0/113 (0.00%)		1/117 (0.85%)
Serious Adverse Events Serious Adverse Events
	Placebo		Reldesemtiv 150 mg Twice Daily		Reldesemtiv 300 mg Twice Daily		Reldesemtiv 450 mg Twice Daily
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/115 (8.70%)		8/112 (7.14%)		8/113 (7.08%)		8/117 (6.84%)
Cardiac disorders
Cardiac failure ^† 1	0/115 (0.00%)	0	0/112 (0.00%)	0	1/113 (0.88%)	1	0/117 (0.00%)	0
Palpitations ^† 1	0/115 (0.00%)	0	0/112 (0.00%)	0	1/113 (0.88%)	1	0/117 (0.00%)	0
Acute myocardial infarction ^† 1	1/115 (0.87%)	1	0/112 (0.00%)	0	0/113 (0.00%)	0	0/117 (0.00%)	0
Gastrointestinal disorders
Dysphagia ^† 1	0/115 (0.00%)	0	2/112 (1.79%)	2	0/113 (0.00%)	0	0/117 (0.00%)	0
Oesophagitis ^† 1	0/115 (0.00%)	0	1/112 (0.89%)	1	0/113 (0.00%)	0	0/117 (0.00%)	0
Rectal prolapse ^† 1	1/115 (0.87%)	1	0/112 (0.00%)	0	0/113 (0.00%)	0	0/117 (0.00%)	0
General disorders
Pain ^† 1	0/115 (0.00%)	0	1/112 (0.89%)	1	0/113 (0.00%)	0	0/117 (0.00%)	0
Hepatobiliary disorders
Hepatotoxicity ^† 1	0/115 (0.00%)	0	0/112 (0.00%)	0	1/113 (0.88%)	1	1/117 (0.85%)	1
Infections and infestations
Urinary tract infection ^† 1	1/115 (0.87%)	1	1/112 (0.89%)	1	1/113 (0.88%)	1	0/117 (0.00%)	0
Appendicitis ^† 1	0/115 (0.00%)	0	1/112 (0.89%)	1	0/113 (0.00%)	0	0/117 (0.00%)	0
Device related sepsis ^† 1	0/115 (0.00%)	0	0/112 (0.00%)	0	1/113 (0.88%)	1	0/117 (0.00%)	0
Parainfluenzae virus infection ^† 1	0/115 (0.00%)	0	0/112 (0.00%)	0	1/113 (0.88%)	1	0/117 (0.00%)	0
Pneumonia ^† 1	1/115 (0.87%)	1	0/112 (0.00%)	0	0/113 (0.00%)	0	0/117 (0.00%)	0
Urosepsis ^† 1	1/115 (0.87%)	1	0/112 (0.00%)	0	0/113 (0.00%)	0	0/117 (0.00%)	0
Injury, poisoning and procedural complications
Head injury ^† 1	0/115 (0.00%)	0	0/112 (0.00%)	0	0/113 (0.00%)	0	1/117 (0.85%)	1
Joint dislocation ^† 1	0/115 (0.00%)	0	1/112 (0.89%)	1	0/113 (0.00%)	0	0/117 (0.00%)	0
Traumatic fracture ^† 1	0/115 (0.00%)	0	0/112 (0.00%)	0	1/113 (0.88%)	1	0/117 (0.00%)	0
Investigations
Alanine aminotransferase increased ^† 1	0/115 (0.00%)	0	0/112 (0.00%)	0	0/113 (0.00%)	0	2/117 (1.71%)	2
Aspartate aminotransferase increased ^† 1	0/115 (0.00%)	0	0/112 (0.00%)	0	0/113 (0.00%)	0	1/117 (0.85%)	1
Blood creatine phosphokinase increased ^† 1	0/115 (0.00%)	0	0/112 (0.00%)	0	0/113 (0.00%)	0	1/117 (0.85%)	1
Glomerular filtration rate decreased ^† 1	0/115 (0.00%)	0	0/112 (0.00%)	0	0/113 (0.00%)	0	1/117 (0.85%)	1
Weight decreased ^† 1	1/115 (0.87%)	1	1/112 (0.89%)	1	0/113 (0.00%)	0	0/117 (0.00%)	0
Nervous system disorders
Amyotrophic lateral sclerosis ^† 1	0/115 (0.00%)	0	0/112 (0.00%)	0	0/113 (0.00%)	0	1/117 (0.85%)	1
Dizziness ^† 1	0/115 (0.00%)	0	0/112 (0.00%)	0	1/113 (0.88%)	2	0/117 (0.00%)	0
Muscle contractions involuntary ^† 1	0/115 (0.00%)	0	1/112 (0.89%)	1	0/113 (0.00%)	0	0/117 (0.00%)	0
Transient ischaemic attack ^† 1	0/115 (0.00%)	0	0/112 (0.00%)	0	0/113 (0.00%)	0	1/117 (0.85%)	1
Renal and urinary disorders
Urinary retention ^† 1	0/115 (0.00%)	0	0/112 (0.00%)	0	1/113 (0.88%)	1	0/117 (0.00%)	0
Reproductive system and breast disorders
Prostatomegaly ^† 1	0/115 (0.00%)	0	0/112 (0.00%)	0	0/113 (0.00%)	0	1/117 (0.85%)	1
Haemorrhagic ovarian cyst ^† 1	1/115 (0.87%)	1	0/112 (0.00%)	0	0/113 (0.00%)	0	0/117 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnoea ^† 1	0/115 (0.00%)	0	1/112 (0.89%)	1	1/113 (0.88%)	1	1/117 (0.85%)	1
Respiratory distress ^† 1	0/115 (0.00%)	0	0/112 (0.00%)	0	1/113 (0.88%)	1	0/117 (0.00%)	0
Pneumonia aspiration ^† 1	2/115 (1.74%)	2	0/112 (0.00%)	0	0/113 (0.00%)	0	0/117 (0.00%)	0
Pulmonary embolism ^† 1	2/115 (1.74%)	2	0/112 (0.00%)	0	0/113 (0.00%)	0	0/117 (0.00%)	0
Vascular disorders
Jugular vein thrombosis ^† 1	1/115 (0.87%)	1	0/112 (0.00%)	0	0/113 (0.00%)	0	0/117 (0.00%)	0
Subclavian vein thrombosis ^† 1	1/115 (0.87%)	1	0/112 (0.00%)	0	0/113 (0.00%)	0	0/117 (0.00%)	0
1 Term from vocabulary, MedDRA 20.0 † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Placebo		Reldesemtiv 150 mg Twice Daily		Reldesemtiv 300 mg Twice Daily		Reldesemtiv 450 mg Twice Daily
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	95/115 (82.61%)		99/112 (88.39%)		97/113 (85.84%)		107/117 (91.45%)
Gastrointestinal disorders
Nausea ^† 1	14/115 (12.17%)	16	10/112 (8.93%)	13	13/113 (11.50%)	14	22/117 (18.80%)	23
Constipation ^† 1	5/115 (4.35%)	5	7/112 (6.25%)	8	13/113 (11.50%)	15	10/117 (8.55%)	10
Diarrhoea ^† 1	8/115 (6.96%)	8	12/112 (10.71%)	15	6/113 (5.31%)	6	4/117 (3.42%)	4
Dry mouth ^† 1	2/115 (1.74%)	2	2/112 (1.79%)	2	6/113 (5.31%)	6	1/117 (0.85%)	1
General disorders
Fatigue ^† 1	12/115 (10.43%)	14	14/112 (12.50%)	14	19/113 (16.81%)	20	20/117 (17.09%)	24
Infections and infestations
Viral upper respiratory tract infection ^† 1	9/115 (7.83%)	9	6/112 (5.36%)	6	10/113 (8.85%)	10	9/117 (7.69%)	9
Urinary tract infection ^† 1	8/115 (6.96%)	9	3/112 (2.68%)	5	5/113 (4.42%)	5	5/117 (4.27%)	7
Upper respiratory tract infection ^† 1	3/115 (2.61%)	4	7/112 (6.25%)	7	1/113 (0.88%)	1	1/117 (0.85%)	1
Injury, poisoning and procedural complications
Contusion ^† 1	15/115 (13.04%)	28	8/112 (7.14%)	15	14/113 (12.39%)	15	17/117 (14.53%)	26
Post-traumatic pain ^† 1	2/115 (1.74%)	2	6/112 (5.36%)	8	8/113 (7.08%)	11	6/117 (5.13%)	6
Skin abrasion ^† 1	5/115 (4.35%)	7	8/112 (7.14%)	10	3/113 (2.65%)	4	5/117 (4.27%)	7
Investigations
Cystatin C increased ^† 1	2/115 (1.74%)	2	7/112 (6.25%)	7	9/113 (7.96%)	9	20/117 (17.09%)	22
Glomerular filtration rate decreased ^† 1	1/115 (0.87%)	1	6/112 (5.36%)	6	6/113 (5.31%)	6	10/117 (8.55%)	11
Alanine aminotransferase increased ^† 1	1/115 (0.87%)	1	2/112 (1.79%)	2	5/113 (4.42%)	6	11/117 (9.40%)	14
Aspartate aminotransferase increased ^† 1	1/115 (0.87%)	1	2/112 (1.79%)	2	3/113 (2.65%)	3	9/117 (7.69%)	11
Metabolism and nutrition disorders
Decreased appetite ^† 1	4/115 (3.48%)	4	3/112 (2.68%)	3	7/113 (6.19%)	7	7/117 (5.98%)	8
Dehydration ^† 1	0/115 (0.00%)	0	1/112 (0.89%)	1	6/113 (5.31%)	6	6/117 (5.13%)	7
Musculoskeletal and connective tissue disorders
Arthralgia ^† 1	2/115 (1.74%)	2	8/112 (7.14%)	9	4/113 (3.54%)	5	8/117 (6.84%)	10
Pain in extremity ^† 1	5/115 (4.35%)	6	1/112 (0.89%)	1	3/113 (2.65%)	3	6/117 (5.13%)	7
Muscle spasms ^† 1	1/115 (0.87%)	1	6/112 (5.36%)	7	2/113 (1.77%)	2	1/117 (0.85%)	1
Nervous system disorders
Headache ^† 1	15/115 (13.04%)	18	16/112 (14.29%)	18	16/113 (14.16%)	19	12/117 (10.26%)	13
Dizziness ^† 1	11/115 (9.57%)	13	8/112 (7.14%)	12	11/113 (9.73%)	13	7/117 (5.98%)	7
Skin and subcutaneous tissue disorders
Pruritus ^† 1	2/115 (1.74%)	4	1/112 (0.89%)	1	2/113 (1.77%)	3	6/117 (5.13%)	6
1 Term from vocabulary, MedDRA 20.0 † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

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

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Name/Title:	MD Cytokinetics
Organization:	Cytokinetics, Inc.
Phone:	650-624-2929
EMail:	medicalaffairs@cytokinetics.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Rudnicki SA, Andrews JA, Genge A, Jackson C, Lechtzin N, Miller TM, Cockroft BM, Malik FI, Meng L, Wei J, Wolff AA, Shefner JM; FORTITUDE-ALS STUDY GROUP. Prescription and acceptance of durable medical equipment in FORTITUDE-ALS, a study of reldesemtiv in ALS: post hoc analyses of a randomized, double-blind, placebo-controlled clinical trial. Amyotroph Lateral Scler Frontotemporal Degener. 2022 May;23(3-4):263-270. doi: 10.1080/21678421.2021.1946083. Epub 2021 Jul 5.

Shefner JM, Andrews JA, Genge A, Jackson C, Lechtzin N, Miller TM, Cockroft BM, Meng L, Wei J, Wolff AA, Malik FI, Bodkin C, Brooks BR, Caress J, Dionne A, Fee D, Goutman SA, Goyal NA, Hardiman O, Hayat G, Heiman-Patterson T, Heitzman D, Henderson RD, Johnston W, Karam C, Kiernan MC, Kolb SJ, Korngut L, Ladha S, Matte G, Mora JS, Needham M, Oskarsson B, Pattee GL, Pioro EP, Pulley M, Quan D, Rezania K, Schellenberg KL, Schultz D, Shoesmith C, Simmons Z, Statland J, Sultan S, Swenson A, Berg LHVD, Vu T, Vucic S, Weiss M, Whyte-Rayson A, Wymer J, Zinman L, Rudnicki SA. A Phase 2, Double-Blind, Randomized, Dose-Ranging Trial Of Reldesemtiv In Patients With ALS. Amyotroph Lateral Scler Frontotemporal Degener. 2021 May;22(3-4):287-299. doi: 10.1080/21678421.2020.1822410. Epub 2020 Sep 24.

Shefner JM, Cudkowicz ME, Hardiman O, Cockcroft BM, Lee JH, Malik FI, Meng L, Rudnicki SA, Wolff AA, Andrews JA; VITALITY-ALS Study Group. A phase III trial of tirasemtiv as a potential treatment for amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener. 2019;0(0):1-11. doi: 10.1080/21678421.2019.1612922. Erratum In: Amyotroph Lateral Scler Frontotemporal Degener. 2019 Jul 14;:1.

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Responsible Party:	Cytokinetics
ClinicalTrials.gov Identifier:	NCT03160898
Other Study ID Numbers:	CY 5022
First Submitted:	May 12, 2017
First Posted:	May 19, 2017
Results First Submitted:	August 5, 2020
Results First Posted:	September 11, 2020
Last Update Posted:	September 11, 2020

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