Amyotrophic Lateral SclerosisPhase 2NCT01486849
Dose Titration Study to Test Safety and Effects of CK-2017357 in Patients With Amyotrophic Lateral Sclerosis (ALS)
A Phase 2 study testing CK-2017357 and Riluzole 50 MG in people with Amyotrophic Lateral Sclerosis, run by Cytokinetics at 11 sites in United States.
Trial summary
A Phase II, double-blind, randomized, placebo-controlled ascending dose titration study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamic effects of multiple ascending doses of CK-2017357 to an individual patient maximum tolerated dose (MTD), using a within-patient twice daily (BID)… 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 and Riluzole 50 MG
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 27 participants
- Where
- 11 sitesUnited States
- Study dates
- Nov 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)
- Able to swallow tablets with water
- Currently taking and tolerating a stable dose of 50 mg BID riluzole
Show all 11Show fewer
- Willing and able to reduce daily dose of riluzole to 50mg QD for 5 weeks
- Not currently taking or willing and able to remain off theophylline-containing medications during study participation
- Patient has a caregiver who is capable of observing and reporting patient status
- Upright Slow Vital Capacity (SVC) >50% of predicted for age, height, and sex
- Able to perform pulmonary function tests
Who cannot join
- Life expectancy <3 months
- Receipt of investigational study drug within 30 days or 5 half-lives of the prior agent, whichever is greater, prior to dosing
- Any prior treatment with CK-2017357
- Any use of non-invasive positive pressure ventilation (NIPPV), such as Continuous Positive Airway Pressure (CPAP) or Bilevel Positive Airway Pressure (BiPAP)
- Other protocol-defined inclusion/exclusion criteria may apply.
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
United States11 sites
Massachusetts General Hospital, Neurology Clinical Trials Unit
Charlestown, Massachusetts, 02129
Ohio State University, Department of Neurology
Columbus, Ohio, 43210
Duke University School of Medicine, Division of Neurology
Durham, North Carolina, 27710
University of California at San Francisco, Fresno Campus, Central California Neurological Institute
Fresno, California, 93701
Coordinated Clinical Research
La Jolla, California, 92037
Hospital for Special Care
New Britain, Connecticut, 06053
Cornell Faculty, Hospital for Special Surgery
New York, New York, 10021
University of California at Irvine, ALS and Neuromuscular Center
Orange, California, 92868
Providence ALS Center
Portland, Oregon, 97213
University of Texas Health Science Center, Department of Neurology
San Antonio, Texas, 78229
Washington University
St Louis, Missouri, 63110
About this study
Official title: A Phase II, Multicenter, Double-Blind, Randomized, Placebo-Controlled Dose Titration Study to Evaluate the Safety, Tolerability and Pharmacodynamic Effects of CK-2017357 in Patients With Amyotrophic Lateral Sclerosis (ALS)
A Phase II, double-blind, randomized, placebo-controlled ascending dose titration study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamic effects of multiple ascending doses of CK-2017357 to an individual patient maximum tolerated dose (MTD), using a within-patient twice daily (BID) dose-titration regimen in ALS patients on 50 mg riluzole once daily (QD).
Read the detailed description
Patients will be randomized to one of two dosing groups, active CK-2017357 or placebo, in a 3:1 ratio. Prior to study drug dosing, patients will be required to decrease their riluzole dose to 50 mg QD for 7 days; after this 7 day period patients will either receive placebo or start the titration on active CK-2017357 while continuing to take riluzole at 50 mg QD.
Potential patients will be screened to assess their eligibility to enter the study within 21 days prior to Day -7, when they will begin taking riluzole at the decreased dose of 50 mg QD. Patients will be randomized in a 3:1 ratio to CK-2017357 (Group 1) or placebo (Group 2). On Day 1, patients will begin taking a total daily dose of 250 mg (125 mg BID) of CK-2017357 or matching placebo tablets BID for 7 days. Then they will take a total daily dose of 375 mg (125 mg morning [AM] and 250 mg evening [PM]) of CK-2017357 or matching placebo tablets BID for 7 days, and finally, they will take a total daily dose of 500 mg (250 mg BID) of CK-2017357 or matching placebo tablets BID for 7 days. A final dose of 250 mg of CK-2017357 or placebo will be taken in the morning on Day 22 at the study site.
Dose-escalation of CK-2017357 or placebo may be stopped, or the dose reduced to a lower level, based on tolerability. All patients who return to a lower dose will stay on that dose for the remainder of the study.
Patients will remain on the decreased dose of riluzole until the follow-up visit approximately 7 days after Day 22.
- Conditions
- Amyotrophic Lateral Sclerosis
- Being tested
- CK-2017357, Placebo, Riluzole 50 MG
- 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.
CK-2017357Drug
Also called tirasemtiv
Total daily oral dose of 250 mg (125 mg BID) of CK-2017357 for 7 days followed by total daily oral dose of 375 mg (125 mg AM and 250 mg PM) for 7 days followed by total daily oral dose of 500 mg (250 mg BID) of CK-2017357 for 7 days
PlaceboDrug
Matching placebo tablets BID for 21 days
Riluzole 50 MGDrug
| Study group | Role | What they receive |
|---|---|---|
| Dose Titration of CK-2017357 (Group 1) | Experimental | Dose titration of active drug as add-on therapy to riluzole Receives: Drug: CK-2017357; Drug: Riluzole 50 MG |
| Matching Placebo (Group 2) | Placebo comparator | Placebo as add-on therapy to riluzole Receives: Drug: Placebo; Drug: Riluzole 50 MG |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with adverse events
Measured: approximately 29 days
Secondary outcomes (11)
Change from baseline in score on the 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. This will be administered at Screening, Day -7, Day 1, Day 15 and Day 22.
Measured: 22 days
Change from baseline in scores on tests of maximum handgrip 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. This will be measured at Screening, Day -7, Day 1, Day 15 and Day 22.
Measured: 22 days
Change from baseline in scores on tests of muscle strength
Muscle strength is measured using Hand Held Dynamometry. A series of assessments are done on different muscle groups. This will be measured at Day -7, Day 1, and Day 22.
Measured: 22 days
Change from baseline in scores on tests of Timed Up and Go
TUG is measured by timing how long it takes for a subject to stand up from a chair, walk 10 feet, turn around, walk back to the chair and sit down. This will be measured at Day -7, Day 1, and Day 22.
Measured: 22 days
Change from baseline in scores on tests 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 15 and Day 22.
Measured: 22 days
Change from baseline in scores on tests of Slow Vital Capacity (SVC)
SVC will be measured using the ndd EasyOne Spirometer System at Screening, Day -7, Day 1, Day 15 and Day 22.
Measured: 22 days
Change from baseline in scores on tests of Maximum Voluntary Ventilation (MVV)
MVV will be measured using the EasyOne Spirometer System at Screening, Day -7, Day 1, Day 15 and Day 22.
Measured: 21 days
Change from baseline in 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: 22 days
Change from baseline in 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: 22 days
Evaluate the pharmacokinetics of CK-2017357
Plasma levels of CK-2017357 will be measured at pre-dose, and at 2 and 4 hours post AM dose
Measured: Day 1, Day 15, and Day 22
Evaluate the pharmacokinetics of riluzole in patients receiving CK-2017357
Plasma levels of riluzole will be measured at pre-dose and at 2 and 4 hours post AM dose
Measured: Day 1, Day 15, and Day 22
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Dec 2011 (estimated)
- Study startNov 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.
- 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
- 27 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
- NCT01486849
- Sponsor's protocol ID
- CY 4025
- Status last verified
- Apr 2019
- First submitted
- 23 Nov 2011
- Last updated
- 3 May 2019
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Multicenter, Double-Blind, Randomized, Placebo-Controlled Dose Titration Study to Evaluate the Safety, Tolerability and Pharmacodynamic Effects of CK-2017357 in Patients With Amyotrophic Lateral Sclerosis (ALS)
- ClinicalTrials.gov ID
- NCT01486849
- Acronym / sponsor ID
- CY 4025
- Conditions
- Amyotrophic Lateral Sclerosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- CytokineticsIndustry (pharma, biotech, devices)
- Study start
- Nov 2011
- Primary completion
- Mar 2012 (actual)
- Study completion
- Mar 2012 (actual)
- First posted
- 7 Dec 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.
A Phase II, double-blind, randomized, placebo-controlled ascending dose titration study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamic effects of multiple ascending doses of CK-2017357 to an individual patient maximum tolerated dose (MTD), using a within-patient twice daily (BID) dose-titration regimen in ALS patients on 50 mg riluzole once daily (QD).
Detailed description
Patients will be randomized to one of two dosing groups, active CK-2017357 or placebo, in a 3:1 ratio. Prior to study drug dosing, patients will be required to decrease their riluzole dose to 50 mg QD for 7 days; after this 7 day period patients will either receive placebo or start the titration on active CK-2017357 while continuing to take riluzole at 50 mg QD.
Potential patients will be screened to assess their eligibility to enter the study within 21 days prior to Day -7, when they will begin taking riluzole at the decreased dose of 50 mg QD. Patients will be randomized in a 3:1 ratio to CK-2017357 (Group 1) or placebo (Group 2). On Day 1, patients will begin taking a total daily dose of 250 mg (125 mg BID) of CK-2017357 or matching placebo tablets BID for 7 days. Then they will take a total daily dose of 375 mg (125 mg morning [AM] and 250 mg evening [PM]) of CK-2017357 or matching placebo tablets BID for 7 days, and finally, they will take a total daily dose of 500 mg (250 mg BID) of CK-2017357 or matching placebo tablets BID for 7 days. A final dose of 250 mg of CK-2017357 or placebo will be taken in the morning on Day 22 at the study site.
Dose-escalation of CK-2017357 or placebo may be stopped, or the dose reduced to a lower level, based on tolerability. All patients who return to a lower dose will stay on that dose for the remainder of the study.
Patients will remain on the decreased dose of riluzole until the follow-up visit approximately 7 days after Day 22.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dose Titration of CK-2017357 (Group 1) | Experimental | Drug: CK-2017357, Drug: Riluzole 50 MGDose titration of active drug as add-on therapy to riluzole |
| Matching Placebo (Group 2) | Placebo comparator | Drug: Placebo, Drug: Riluzole 50 MGPlacebo as add-on therapy to riluzole |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 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)
- Able to swallow tablets with water
Key exclusion criteria (5 listed)
- Life expectancy <3 months
- Receipt of investigational study drug within 30 days or 5 half-lives of the prior agent, whichever is greater, prior to dosing
- Any prior treatment with CK-2017357
- Any use of non-invasive positive pressure ventilation (NIPPV), such as Continuous Positive Airway Pressure (CPAP) or Bilevel Positive Airway Pressure (BiPAP)
- 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 |
|---|---|---|
| CK-2017357Also: tirasemtivTotal daily oral dose of 250 mg (125 mg BID) of CK-2017357 for 7 days followed by total daily oral dose of 375 mg (125 mg AM and 250 mg PM) for 7 days followed by total daily oral dose of 500 mg (250 mg BID) of CK-2017357 for 7 days | Drug | Dose Titration of CK-2017357 (Group 1) |
| PlaceboMatching placebo tablets BID for 21 days | Drug | Matching Placebo (Group 2) |
| Riluzole 50 MG | Drug | Dose Titration of CK-2017357 (Group 1), Matching Placebo (Group 2) |
Primary outcome
Number of participants with adverse events
Time frame: approximately 29 days
11 secondary outcomes
Change from baseline in score on the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R)
Time frame: 22 days
Change from baseline in scores on tests of maximum handgrip strength and handgrip fatigue
Time frame: 22 days
Change from baseline in scores on tests of muscle strength
Time frame: 22 days
Change from baseline in scores on tests of Timed Up and Go
Time frame: 22 days
Change from baseline in scores on tests of Sniff Nasal Inspiratory Pressure (SNIP)
Time frame: 22 days
Change from baseline in scores on tests of Slow Vital Capacity (SVC)
Time frame: 22 days
Change from baseline in scores on tests of Maximum Voluntary Ventilation (MVV)
Time frame: 21 days
Change from baseline in Patient Global Assessment
Time frame: 22 days
Change from baseline in Investigator Global Assessment
Time frame: 22 days
Evaluate the pharmacokinetics of CK-2017357
Time frame: Day 1, Day 15, and Day 22
Evaluate the pharmacokinetics of riluzole in patients receiving CK-2017357
Time frame: Day 1, Day 15, and Day 22
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 3 May 2019.
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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
11 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 and Riluzole 50 MG in people with Amyotrophic Lateral Sclerosis, run by Cytokinetics at 11 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 11 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 3 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 11 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 (time frame: approximately 29 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 3 May 2019.