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A Study to Evaluate the Effects of Multiple Doses of CK-2017357 in Patients With Amyotrophic Lateral Sclerosis (ALS)

Primary Purpose

Amyotrophic Lateral Sclerosis

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Placebo (Part A)
CK-2017357 (Part A)
CK-2017357 (Part A)
CK-2017357 (Part A)
Riluzole 50 MG (Part B)
Placebo (Part B)
CK-2017357 (Part B)
CK-2017357 (Part B)
CK-2017357 (Part B)
Sponsored by
Cytokinetics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Amyotrophic Lateral Sclerosis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Key Inclusion Criteria:

  1. Able to comprehend and willing to sign an Informed Consent Form (ICF)
  2. Males or females 18 years of age or older
  3. 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)
  4. Maximum voluntary grip strength in at least one hand between 10 & 40 pounds (females) and 10 & 60 pounds (males)
  5. Upright Slow Vital Capacity (SVC) >50% of predicted for age, height, and sex
  6. Able to swallow tablets with water
  7. Willing and able to remain off riluzole for 4 weeks (Part A only)
  8. Currently taking and tolerating a stable dose of 50 mg BID riluzole (Part B only)
  9. Willing and able to reduce daily dose of riluzole to 50 mg for 4 weeks (Part B only)
  10. Willing and able to refrain from caffeine-containing products during study participation
  11. Willing and able to remain off warfarin and theophylline-containing medications during study participation
  12. Has a caregiver who is capable of observing and reporting patient status, and also assisting in the proper use of nocturnal oximetry equipment
  13. Able to perform pulmonary function tests

Key Exclusion Criteria:

  1. Life expectancy <3 months
  2. 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
  3. Any prior treatment with CK-2017357
  4. Use of non-invasive positive pressure ventilation (NIPPV) for any part of the day or night

Other protocol-defined inclusion/exclusion criteria may apply.

Sites / Locations

  • California Pacific Medical Center
  • Mayo Florida
  • University of Kansas
  • Johns Hopkins Hospital
  • Columbia University Medical Center
  • SUNY Upstate Medical Center
  • Carolinas Neuromuscular ALS-MND Center
  • Penn State Hershey Medical Center
  • Drexel University College of Medicine

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Placebo Comparator

Experimental

Experimental

Experimental

Arm Label

Matching Placebo

Active Drug Low Dose (CK-2017357 125 mg)

Active Drug Mid Dose (CK-2017357 250 mg)

Active Drug High Dose (CK-2017357 375 mg)

Arm Description

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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.
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.
Measurement of muscle strength
Muscle strength is measured using Hand Held Dynamometry. A series of assessments are done on different muscle groups.
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
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
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
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
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.

Full Information

First Posted
June 20, 2011
Last Updated
May 2, 2019
Sponsor
Cytokinetics
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1. Study Identification

Unique Protocol Identification Number
NCT01378676
Brief Title
A Study to Evaluate the Effects of Multiple Doses of CK-2017357 in Patients With Amyotrophic Lateral Sclerosis (ALS)
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)
Study Type
Interventional

2. Study Status

Record Verification Date
May 2019
Overall Recruitment Status
Completed
Study Start Date
June 2011 (undefined)
Primary Completion Date
March 2012 (Actual)
Study Completion Date
March 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cytokinetics

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Amyotrophic Lateral Sclerosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
49 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Matching Placebo
Arm Type
Placebo Comparator
Arm Title
Active Drug Low Dose (CK-2017357 125 mg)
Arm Type
Experimental
Arm Title
Active Drug Mid Dose (CK-2017357 250 mg)
Arm Type
Experimental
Arm Title
Active Drug High Dose (CK-2017357 375 mg)
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Placebo (Part A)
Intervention Description
Placebo tablets once daily for 14 days (Part A)
Intervention Type
Drug
Intervention Name(s)
CK-2017357 (Part A)
Other Intervention Name(s)
tirasemtiv
Intervention Description
One 125 mg CK-2017357 tablet once daily for 14 days (Part A)
Intervention Type
Drug
Intervention Name(s)
CK-2017357 (Part A)
Other Intervention Name(s)
tirasemtiv
Intervention Description
Two 125 mg CK-2017357 tablets once daily for 14 days (Part A)
Intervention Type
Drug
Intervention Name(s)
CK-2017357 (Part A)
Other Intervention Name(s)
tirasemtiv
Intervention Description
Three 125 mg CK-2017357 tablets once daily for 14 days (Part A)
Intervention Type
Drug
Intervention Name(s)
Riluzole 50 MG (Part B)
Intervention Description
One 50 mg tablet once daily for 14 days (Part B)
Intervention Type
Drug
Intervention Name(s)
Placebo (Part B)
Intervention Description
Placebo tablets once daily for 14 days (Part B)
Intervention Type
Drug
Intervention Name(s)
CK-2017357 (Part B)
Other Intervention Name(s)
tirasemtiv
Intervention Description
One 125 mg tablet once daily for 14 days (Part B)
Intervention Type
Drug
Intervention Name(s)
CK-2017357 (Part B)
Other Intervention Name(s)
tirasemtiv
Intervention Description
Two 125 mg tablets once daily for 14 days (Part B)
Intervention Type
Drug
Intervention Name(s)
CK-2017357 (Part B)
Other Intervention Name(s)
tirasemtiv
Intervention Description
Three 125 mg tablets once daily for 14 days (Part B)
Primary Outcome Measure Information:
Title
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Description
Safety and tolerability of CK-2017357 after multiple oral doses to steady state in patients with ALS
Time Frame
21 days
Secondary Outcome Measure Information:
Title
Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R)
Description
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.
Time Frame
21 days
Title
Measurement of Grip Strength and Handgrip Fatigue
Description
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.
Time Frame
21 days
Title
Measurement of muscle strength
Description
Muscle strength is measured using Hand Held Dynamometry. A series of assessments are done on different muscle groups.
Time Frame
21 days
Title
Measurement of Slow Vital Capacity (SVC)
Description
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
Time Frame
21 days
Title
Measurement of Sniff Nasal Inspiratory Pressure (SNIP)
Description
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
Time Frame
21 days
Title
Measurement of Maximum Voluntary Ventilation (MVV)
Description
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
Time Frame
21 days
Title
Patient global assessment
Description
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
Time Frame
15 days
Title
Investigator global assessment
Description
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.
Time Frame
15 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria: 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 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 Key Exclusion Criteria: 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jeremy Shefner, MD, PhD
Organizational Affiliation
State University of New York - Upstate Medical University
Official's Role
Study Chair
Facility Information:
Facility Name
California Pacific Medical Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
Facility Name
Mayo Florida
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Facility Name
University of Kansas
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
06053
Country
United States
Facility Name
Johns Hopkins Hospital
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
SUNY Upstate Medical Center
City
Syracuse
State/Province
New York
ZIP/Postal Code
13210
Country
United States
Facility Name
Carolinas Neuromuscular ALS-MND Center
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28207
Country
United States
Facility Name
Penn State Hershey Medical Center
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033
Country
United States
Facility Name
Drexel University College of Medicine
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
23952636
Citation
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.
Results Reference
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A Study to Evaluate the Effects of Multiple Doses of CK-2017357 in Patients With Amyotrophic Lateral Sclerosis (ALS)

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