Dose Titration Study to Test Safety and Effects of CK-2017357 in Patients With Amyotrophic Lateral Sclerosis (ALS)

NCT ID: NCT01486849

Last Updated: 2019-05-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

27 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-11-30

Study Completion Date

2012-03-31

Brief Summary

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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

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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

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Amyotrophic Lateral Sclerosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Dose Titration of CK-2017357 (Group 1)

Dose titration of active drug as add-on therapy to riluzole

Group Type EXPERIMENTAL

CK-2017357

Intervention Type DRUG

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

Riluzole 50 MG

Intervention Type DRUG

Matching Placebo (Group 2)

Placebo as add-on therapy to riluzole

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Matching placebo tablets BID for 21 days

Riluzole 50 MG

Intervention Type DRUG

Interventions

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CK-2017357

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

Intervention Type DRUG

Placebo

Matching placebo tablets BID for 21 days

Intervention Type DRUG

Riluzole 50 MG

Intervention Type DRUG

Other Intervention Names

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tirasemtiv

Eligibility Criteria

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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. Able to swallow tablets with water
6. Currently taking and tolerating a stable dose of 50 mg BID riluzole
7. Willing and able to reduce daily dose of riluzole to 50mg QD for 5 weeks
8. Not currently taking or willing and able to remain off theophylline-containing medications during study participation
9. Patient has a caregiver who is capable of observing and reporting patient status
10. Upright Slow Vital Capacity (SVC) \>50% of predicted for age, height, and sex
11. Able to perform pulmonary function tests

Exclusion Criteria

1. Life expectancy \<3 months
2. Receipt of investigational study drug 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. Any use of non-invasive positive pressure ventilation (NIPPV), such as Continuous Positive Airway Pressure (CPAP) or Bilevel Positive Airway Pressure (BiPAP)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Cytokinetics

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jeremy Shefner, MD, PhD

Role: STUDY_CHAIR

State University of New York - Upstate Medical University

Locations

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University of California at San Francisco, Fresno Campus, Central California Neurological Institute

Fresno, California, United States

Site Status

Coordinated Clinical Research

La Jolla, California, United States

Site Status

University of California at Irvine, ALS and Neuromuscular Center

Orange, California, United States

Site Status

Hospital for Special Care

New Britain, Connecticut, United States

Site Status

Massachusetts General Hospital, Neurology Clinical Trials Unit

Charlestown, Massachusetts, United States

Site Status

Washington University

St Louis, Missouri, United States

Site Status

Cornell Faculty, Hospital for Special Surgery

New York, New York, United States

Site Status

Duke University School of Medicine, Division of Neurology

Durham, North Carolina, United States

Site Status

Ohio State University, Department of Neurology

Columbus, Ohio, United States

Site Status

Providence ALS Center

Portland, Oregon, United States

Site Status

University of Texas Health Science Center, Department of Neurology

San Antonio, Texas, United States

Site Status

Countries

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United States

Other Identifiers

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CY 4025

Identifier Type: -

Identifier Source: org_study_id

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