Amyotrophic Lateral SclerosisPhase 2NCT01378676
A Study to Evaluate the Effects of Multiple Doses of CK-2017357 in Patients With Amyotrophic Lateral Sclerosis (ALS)
A Phase 2 study testing CK-2017357 (Part A), Riluzole 50 MG (Part B) and CK-2017357 (Part B) in people with Amyotrophic Lateral Sclerosis, run by Cytokinetics at 9 sites in United States.
Trial summary
The study will generate data on safety, tolerability and pharmacokinetics after multiple daily doses of CK-2017357 in patients with ALS. Patients will be randomized into one of four different treatment groups, receiving daily oral doses of either placebo, 125 mg, 250 mg, or 375 mg of CK-2017357 for 14 days. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Amyotrophic Lateral Sclerosis
- What is being tested?
- CK-2017357 (Part A), Riluzole 50 MG (Part B) and CK-2017357 (Part B)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 49 participants
- Where
- 9 sitesUnited States
- Study dates
- Jun 2011to Mar 2012
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Able to comprehend and willing to sign an Informed Consent Form (ICF)
- Males or females 18 years of age or older
- A 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)
- Maximum voluntary grip strength in at least one hand between 10 \& 40 pounds (females) and 10 \& 60 pounds (males)
- Upright Slow Vital Capacity (SVC) >50% of predicted for age, height, and sex
- Able to swallow tablets with water
Show all 13Show fewer
- Willing and able to remain off riluzole for 4 weeks (Part A only)
- Currently taking and tolerating a stable dose of 50 mg BID riluzole (Part B only)
- Willing and able to reduce daily dose of riluzole to 50 mg for 4 weeks (Part B only)
- Willing and able to refrain from caffeine-containing products during study participation
- Willing and able to remain off warfarin and theophylline-containing medications during study participation
- Has a caregiver who is capable of observing and reporting patient status, and also assisting in the proper use of nocturnal oximetry equipment
- Able to perform pulmonary function tests
Who cannot join
- Life expectancy <3 months
- Participation in any trial in which receipt of investigational study drug occurred within 30 days or 5 half-lives of the prior agent, whichever is greater, prior to dosing
- Any prior treatment with CK-2017357
- Use of non-invasive positive pressure ventilation (NIPPV) for any part of the day or night
- Other protocol-defined inclusion/exclusion criteria may apply.
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United States9 sites
Johns Hopkins Hospital
Baltimore, Maryland, 21287
Carolinas Neuromuscular ALS-MND Center
Charlotte, North Carolina, 28207
Penn State Hershey Medical Center
Hershey, Pennsylvania, 17033
Mayo Florida
Jacksonville, Florida, 32224
University of Kansas
Kansas City, Kansas, 06053
Columbia University Medical Center
New York, New York, 10032
Drexel University College of Medicine
Philadelphia, Pennsylvania, 19107
California Pacific Medical Center
San Francisco, California, 94115
SUNY Upstate Medical Center
Syracuse, New York, 13210
About this study
Official title: A Phase II, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Effects of Multiple Doses of CK-2017357 in Patients With Amyotrophic Lateral Sclerosis (ALS)
The study will generate data on safety, tolerability and pharmacokinetics after multiple daily doses of CK-2017357 in patients with ALS. Patients will be randomized into one of four different treatment groups, receiving daily oral doses of either placebo, 125 mg, 250 mg, or 375 mg of CK-2017357 for 14 days.
Read the detailed description
In Part A, approximately 24 patients will be randomized to one of four different treatment groups. After a 7-day washout of riluzole, patients in each treatment group will receive daily oral doses of placebo, 125 mg, 250 mg, or 375 mg of CK-2017357 for 14 days. Patients will take daily doses of CK-2017357 or placebo (Day 1 through Day 14) and will return to the study site on Day 2, Day 8 and Day 15. All patients will return for a follow-up visit 7 days (± 2 days) after their last dose.
In Part B, approximately additional 24 patients will be randomized to one of four different treatment groups as in Part A. Patients in Part B will be required to decrease their riluzole dose to 50 mg once a day (QD) for 7 days prior to randomization. After this 7 day period, patients will take riluzole at 50 mg QD concurrently with their morning dose of blinded study drug.
- Conditions
- Amyotrophic Lateral Sclerosis
- Being tested
- Placebo (Part A), CK-2017357 (Part A), Riluzole 50 MG (Part B), Placebo (Part B), CK-2017357 (Part B)
- Medical subject headings
- Amyotrophic Lateral Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Placebo (Part A)Drug
Placebo tablets once daily for 14 days (Part A)
CK-2017357 (Part A)Drug
Also called tirasemtiv
One 125 mg CK-2017357 tablet once daily for 14 days (Part A)
CK-2017357 (Part A)Drug
Also called tirasemtiv
Two 125 mg CK-2017357 tablets once daily for 14 days (Part A)
CK-2017357 (Part A)Drug
Also called tirasemtiv
Three 125 mg CK-2017357 tablets once daily for 14 days (Part A)
Riluzole 50 MG (Part B)Drug
One 50 mg tablet once daily for 14 days (Part B)
Placebo (Part B)Drug
Placebo tablets once daily for 14 days (Part B)
CK-2017357 (Part B)Drug
Also called tirasemtiv
One 125 mg tablet once daily for 14 days (Part B)
CK-2017357 (Part B)Drug
Also called tirasemtiv
Two 125 mg tablets once daily for 14 days (Part B)
CK-2017357 (Part B)Drug
Also called tirasemtiv
Three 125 mg tablets once daily for 14 days (Part B)
| Study group | Role | What they receive |
|---|---|---|
| Matching Placebo | Placebo comparator | Not described Receives: Drug: Placebo (Part A); Drug: Riluzole 50 MG (Part B); Drug: Placebo (Part B) |
| Active Drug Low Dose (CK-2017357 125 mg) | Experimental | Not described Receives: Drug: Placebo (Part A); Drug: CK-2017357 (Part A); Drug: Riluzole 50 MG (Part B); Drug: Placebo (Part B); Drug: CK-2017357 (Part B) |
| Active Drug Mid Dose (CK-2017357 250 mg) | Experimental | Not described Receives: Drug: Placebo (Part A); Drug: CK-2017357 (Part A); Drug: Riluzole 50 MG (Part B); Drug: Placebo (Part B); Drug: CK-2017357 (Part B) |
| Active Drug High Dose (CK-2017357 375 mg) | Experimental | Not described Receives: Drug: CK-2017357 (Part A); Drug: Riluzole 50 MG (Part B); Drug: CK-2017357 (Part B) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Safety and tolerability of CK-2017357 after multiple oral doses to steady state in patients with ALS
Measured: 21 days
Secondary outcomes (8)
Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R)
An instrument for evaluating the functional status of patients with ALS. Minimum score is 0 and maximum score is 40. The higher the score the more function is retained.
Measured: 21 days
Measurement of Grip Strength and Handgrip Fatigue
Measured using the DynEx Electronic Hand Dynamometer. Patients asked to squeeze the device with the maximum possible force to establish the maximum voluntary contraction. Handgrip fatigue is then measured. Patient is asked to squeeze the device until they can no longer stay above 60% of target or 120 seconds.
Measured: 21 days
Measurement of muscle strength
Muscle strength is measured using Hand Held Dynamometry. A series of assessments are done on different muscle groups.
Measured: 21 days
Measurement of Slow Vital Capacity (SVC)
SVC will be measured using the ndd EasyOne Spirometer System at Screening, Day -7, Day 1, Day 2, Day 8, Day 15 and at the Follow-Up Visit
Measured: 21 days
Measurement of Sniff Nasal Inspiratory Pressure (SNIP)
SNIP will be measured using the Micro Medical Respiratory Pressure Meter (MicroRPM) at Screening, Day -7, Day 1, Day 2, Day 8, Day 15 and at the Follow-Up Visit
Measured: 21 days
Measurement of Maximum Voluntary Ventilation (MVV)
MVV will be measured using the EasyOne Spirometer System at Screening, Day -7, Day 1, Day 2, Day 8, Day 15 and at the Follow-Up Visit
Measured: 21 days
Patient global assessment
Patients will be asked to assess whether they feel the same, better or worse as compared to how they felt at pre-dose on Day 1
Measured: 15 days
Investigator global assessment
Investigator will assess whether the patient appears the same, better or worse as compared to the patient's status at pre-dose on Day 1.
Measured: 15 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jun 2011 (estimated)
- Study startJun 2011
- Primary completionMar 2012
- Study completionMar 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Amyotrophic Lateral SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cytokinetics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jeremy Shefner, MD, PhD, Study chair, State University of New York - Upstate Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01378676
- Sponsor's protocol ID
- CY 4024
- Status last verified
- May 2019
- First submitted
- 20 Jun 2011
- Last updated
- 7 May 2019
- Results posted
- No
- Data monitoring committee
- No
Publications
Shefner JM, Watson ML, Meng L, Wolff AA; Neals/Cytokinetics STUDY Team. A study to evaluate safety and tolerability of repeated doses of tirasemtiv in patients with amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener. 2013 Dec;14(7-8):574-81. doi: 10.3109/21678421.2013.822517. Epub 2013 Aug 19.
PubMed 23952636
Study at a glance
From the registry record, last updated by the sponsor on 7 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Effects of Multiple Doses of CK-2017357 in Patients With Amyotrophic Lateral Sclerosis (ALS)
- ClinicalTrials.gov ID
- NCT01378676
- Acronym / sponsor ID
- CY 4024
- Conditions
- Amyotrophic Lateral Sclerosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 49 participants (actual)
- Lead sponsor
- CytokineticsIndustry (pharma, biotech, devices)
- Study start
- Jun 2011
- Primary completion
- Mar 2012 (actual)
- Study completion
- Mar 2012 (actual)
- First posted
- 22 Jun 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study will generate data on safety, tolerability and pharmacokinetics after multiple daily doses of CK-2017357 in patients with ALS. Patients will be randomized into one of four different treatment groups, receiving daily oral doses of either placebo, 125 mg, 250 mg, or 375 mg of CK-2017357 for 14 days.
Detailed description
In Part A, approximately 24 patients will be randomized to one of four different treatment groups. After a 7-day washout of riluzole, patients in each treatment group will receive daily oral doses of placebo, 125 mg, 250 mg, or 375 mg of CK-2017357 for 14 days. Patients will take daily doses of CK-2017357 or placebo (Day 1 through Day 14) and will return to the study site on Day 2, Day 8 and Day 15. All patients will return for a follow-up visit 7 days (± 2 days) after their last dose.
In Part B, approximately additional 24 patients will be randomized to one of four different treatment groups as in Part A. Patients in Part B will be required to decrease their riluzole dose to 50 mg once a day (QD) for 7 days prior to randomization. After this 7 day period, patients will take riluzole at 50 mg QD concurrently with their morning dose of blinded study drug.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Matching Placebo | Placebo comparator | Drug: Placebo (Part A), Drug: Riluzole 50 MG (Part B), Drug: Placebo (Part B) |
| Active Drug Low Dose (CK-2017357 125 mg) | Experimental | Drug: Placebo (Part A), Drug: CK-2017357 (Part A), Drug: Riluzole 50 MG (Part B), Drug: Placebo (Part B), Drug: CK-2017357 (Part B) |
| Active Drug Mid Dose (CK-2017357 250 mg) | Experimental | Drug: Placebo (Part A), Drug: CK-2017357 (Part A), Drug: Riluzole 50 MG (Part B), Drug: Placebo (Part B), Drug: CK-2017357 (Part B) |
| Active Drug High Dose (CK-2017357 375 mg) | Experimental | Drug: CK-2017357 (Part A), Drug: Riluzole 50 MG (Part B), Drug: CK-2017357 (Part B) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Able to comprehend and willing to sign an Informed Consent Form (ICF)
- Males or females 18 years of age or older
- A 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)
- Maximum voluntary grip strength in at least one hand between 10 \& 40 pounds (females) and 10 \& 60 pounds (males)
- Upright Slow Vital Capacity (SVC) >50% of predicted for age, height, and sex
Key exclusion criteria (5 listed)
- Life expectancy <3 months
- Participation in any trial in which receipt of investigational study drug occurred within 30 days or 5 half-lives of the prior agent, whichever is greater, prior to dosing
- Any prior treatment with CK-2017357
- Use of non-invasive positive pressure ventilation (NIPPV) for any part of the day or night
- Other protocol-defined inclusion/exclusion criteria may apply.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Placebo (Part A)Placebo tablets once daily for 14 days (Part A) | Drug | Active Drug Low Dose (CK-2017357 125 mg), Active Drug Mid Dose (CK-2017357 250 mg), Matching Placebo |
| CK-2017357 (Part A)Also: tirasemtivOne 125 mg CK-2017357 tablet once daily for 14 days (Part A) | Drug | Active Drug Low Dose (CK-2017357 125 mg) |
| CK-2017357 (Part A)Also: tirasemtivTwo 125 mg CK-2017357 tablets once daily for 14 days (Part A) | Drug | Active Drug Mid Dose (CK-2017357 250 mg) |
| CK-2017357 (Part A)Also: tirasemtivThree 125 mg CK-2017357 tablets once daily for 14 days (Part A) | Drug | Active Drug High Dose (CK-2017357 375 mg) |
| Riluzole 50 MG (Part B)One 50 mg tablet once daily for 14 days (Part B) | Drug | Active Drug High Dose (CK-2017357 375 mg), Active Drug Low Dose (CK-2017357 125 mg), Active Drug Mid Dose (CK-2017357 250 mg), Matching Placebo |
| Placebo (Part B)Placebo tablets once daily for 14 days (Part B) | Drug | Active Drug Low Dose (CK-2017357 125 mg), Active Drug Mid Dose (CK-2017357 250 mg), Matching Placebo |
| CK-2017357 (Part B)Also: tirasemtivOne 125 mg tablet once daily for 14 days (Part B) | Drug | Active Drug Low Dose (CK-2017357 125 mg) |
| CK-2017357 (Part B)Also: tirasemtivTwo 125 mg tablets once daily for 14 days (Part B) | Drug | Active Drug Mid Dose (CK-2017357 250 mg) |
| CK-2017357 (Part B)Also: tirasemtivThree 125 mg tablets once daily for 14 days (Part B) | Drug | Active Drug High Dose (CK-2017357 375 mg) |
Primary outcome
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Time frame: 21 days
Safety and tolerability of CK-2017357 after multiple oral doses to steady state in patients with ALS
8 secondary outcomes
Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R)
Time frame: 21 days
Measurement of Grip Strength and Handgrip Fatigue
Time frame: 21 days
Measurement of muscle strength
Time frame: 21 days
Measurement of Slow Vital Capacity (SVC)
Time frame: 21 days
Measurement of Sniff Nasal Inspiratory Pressure (SNIP)
Time frame: 21 days
Measurement of Maximum Voluntary Ventilation (MVV)
Time frame: 21 days
Patient global assessment
Time frame: 15 days
Investigator global assessment
Time frame: 15 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 May 2019.
- Results publication: PubMed 23952636Shefner JM, Watson ML, Meng L, Wolff AA; Neals/Cytokinetics STUDY Team. A study to evaluate safety and tolerability of repeated doses of tirasemtiv in patients with amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener. 2013 Dec;14(7-8):574-81. doi: 10.3109/21678421.2013.822517. Epub 2013 Aug 19.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jeremy Shefner, MD, PhD study chair
State University of New York - Upstate Medical University
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing CK-2017357 (Part A), Riluzole 50 MG (Part B) and CK-2017357 (Part B) in people with Amyotrophic Lateral Sclerosis, run by Cytokinetics at 9 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 May 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants with Adverse Events as a Measure of Safety and Tolerability (time frame: 21 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01378676, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 May 2019.