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

Amyotrophic Lateral Sclerosis Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01378676
• Other study ID #: CY 4024
• Status: Completed
• Phase: Phase 2
• Start date: June 2011
• Est. completion date: March 2012

Study information

• Verified date: May 2019
• Source: Cytokinetics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: March 2012
• Est. primary completion date: March 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease
• Sclerosis

Intervention

Drug:
• Placebo (Part A)
Placebo tablets once daily for 14 days (Part A)
• CK-2017357 (Part A)
One 125 mg CK-2017357 tablet once daily for 14 days (Part A)
• CK-2017357 (Part A)
Two 125 mg CK-2017357 tablets once daily for 14 days (Part A)
• CK-2017357 (Part A)
Three 125 mg CK-2017357 tablets once daily for 14 days (Part A)
• Riluzole 50 MG (Part B)
One 50 mg tablet once daily for 14 days (Part B)
• Placebo (Part B)
Placebo tablets once daily for 14 days (Part B)
• CK-2017357 (Part B)
One 125 mg tablet once daily for 14 days (Part B)
• CK-2017357 (Part B)
Two 125 mg tablets once daily for 14 days (Part B)
• CK-2017357 (Part B)
Three 125 mg tablets once daily for 14 days (Part B)

Locations

Country	Name	City	State
United States	Johns Hopkins Hospital	Baltimore	Maryland
United States	Carolinas Neuromuscular ALS-MND Center	Charlotte	North Carolina
United States	Penn State Hershey Medical Center	Hershey	Pennsylvania
United States	Mayo Florida	Jacksonville	Florida
United States	University of Kansas	Kansas City	Kansas
United States	Columbia University Medical Center	New York	New York
United States	Drexel University College of Medicine	Philadelphia	Pennsylvania
United States	California Pacific Medical Center	San Francisco	California
United States	SUNY Upstate Medical Center	Syracuse	New York

Sponsors (1)

Lead Sponsor	Collaborator
Cytokinetics

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	21 days
Secondary	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.	21 days
Secondary	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.	21 days
Secondary	Measurement of muscle strength	Muscle strength is measured using Hand Held Dynamometry. A series of assessments are done on different muscle groups.	21 days
Secondary	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	21 days
Secondary	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	21 days
Secondary	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	21 days
Secondary	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	15 days
Secondary	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.	15 days