A Study of CK-2017357 in Patients With Amyotrophic Lateral Sclerosis (ALS)

NCT01089010 | Completed Phase 2

• 1 other identifier: CY 4021
• Study Type: interventional
• Target: 67
• Locations: 1 country
• Sites: 15

Brief Summary

The primary objective of this study is to demonstrate a pharmacodynamic effect of CK 2017357 on measures of skeletal muscle function or fatigability in patients with ALS.

Conditions

Amyotrophic Lateral Sclerosis

Outcome Measures

Primary Outcomes (9)

• 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.

  2 days

• Maximum grip strength

  Measured using the DynEx Electronic Hand Dynamometer. Patients asked to squeeze the device with the maximum possible force to establish the maximum voluntary contraction.

  2 days

• Maximum grip strength fatigability

  Handgrip fatigue is measured using the DynEx Electronic Hand Dynamometer. Patient is asked to squeeze the device until they can no longer stay above 60% of target or 120 seconds.

  2 days

• Shoulder extension fatigue

  Patient is asked to hold one arm outstretched in front of them at a 90 degree angle. The time the arm falls below 90 degrees for \> 2 seconds will be recorded, up to a total evaluation time of 2 minutes. This is then repeated with the other arm.

  2 days

• Slow Vital Capacity (SVC)

  SVC is measured using the Puritan Bennett Renaissance II Spirometry System and accessories.

  2 days

• Maximum Voluntary Ventilation (MVV)

  MVV is the volume of air that can be exhaled during 12 seconds of rapid deep breathing. The actual volume is extrapolated to one minute. the Puritan Bennett Renaissance II Spirometry System and accessories is used for this measurement.

  2 days

• Sniff Inspiratory Pressure (SNIP)

  SNIP is measured at Functional Residual Capacity, the bottom of the tidal breathing cycle, through one plugged nostril while the other remains open using the Micro Medical MicroRPM Respiratory Pressure Meter

  2 days

• Maximum Voluntary Muscle Contraction (MVC)

  MVC is measured using the MicroFET 2 HHD.

  2 days

• Repeated Sub-Maximum Grip Strength Fatigability

  Sub-Maximum Grip Strength Fatigability is measured using the DynEx Electronic Hand. Dynamometer

  2 days

Secondary Outcomes (12)

• Characterize the relationship, if any, between the plasma concentration of CK-2017357 and ALSFRS-R.

  2 days

• Characterize the relationship, if any, between the plasma concentration of CK-2017357 and maximum grip strength

  2 days

• Characterize the relationship, if any, between the plasma concentration of CK-2017357 and maximum grip strength fatigability

  2 days

• Characterize the relationship, if any, between the plasma concentration of CK-2017357 and shoulder extension fatigue

  2 days

• Characterize the relationship, if any, between the plasma concentration of CK-2017357 and slow vital capacity

  2 days

Study Arms (6)

Treatment Sequence 1

EXPERIMENTAL

Treatment sequence 1 consisted of three dosing periods in which patients received single oral doses of placebo, 250 mg, and 500 mg of CK-2017357, in that order, with approximately one week between each dose. Each patient acted as their own control, as all doses were represented in each treatment sequence.

Drug: Placebo; Drug: 250 mg CK-2017357; Drug: 500 mg CK-2017357

Treatment Sequence 2

EXPERIMENTAL

Treatment sequence 2 consisted of three dosing periods in which patients received single oral doses of placebo, 500 mg, and 250 mg of CK-2017357, in that order, with approximately one week between each dose. Each patient acted as their own control, as all doses were represented in each treatment sequence.

Drug: Placebo; Drug: 250 mg CK-2017357; Drug: 500 mg CK-2017357

Treatment Sequence 3

EXPERIMENTAL

Treatment sequence 3 consisted of three dosing periods in which patients received single oral doses of 250 mg, placebo and 500 mg of CK-2017357, in that order, with approximately one week between each dose. Each patient acted as their own control, as all doses were represented in each treatment sequence.

Drug: Placebo; Drug: 250 mg CK-2017357; Drug: 500 mg CK-2017357

Treatment Sequence 4

EXPERIMENTAL

Treatment sequence 4 consisted of three dosing periods in which patients received single oral doses of 250 mg, 500 mg and placebo of CK-2017357, in that order, with approximately one week between each dose. Each patient acted as their own control, as all doses were represented in each treatment sequence.

Drug: Placebo; Drug: 250 mg CK-2017357; Drug: 500 mg CK-2017357

Treatment Sequence 5

EXPERIMENTAL

Treatment sequence 5 consisted of three dosing periods in which patients received single oral doses of 500 mg, placebo, and 250 mg of CK-2017357, in that order, with approximately one week between each dose. Each patient acted as their own control, as all doses were represented in each treatment sequence.

Drug: Placebo; Drug: 250 mg CK-2017357; Drug: 500 mg CK-2017357

Treatment Sequence 6

EXPERIMENTAL

Treatment sequence6 consisted of three dosing periods in which patients received single oral doses of 500 mg, 250 mg, and placebo of CK-2017357, in that order, with approximately one week between each dose. Each patient acted as their own control, as all doses were represented in each treatment sequence.

Drug: Placebo; Drug: 250 mg CK-2017357; Drug: 500 mg CK-2017357

Interventions

Placebo DRUG

Matching placebo in capsules administered as a single oral dose.

Treatment Sequence 1; Treatment Sequence 2; Treatment Sequence 3; Treatment Sequence 4; Treatment Sequence 5; Treatment Sequence 6

250 mg CK-2017357 DRUG

250 mg CK-2017357 in capsules administered as a single oral dose.

Also known as: tirasemtiv

Treatment Sequence 1; Treatment Sequence 2; Treatment Sequence 3; Treatment Sequence 4; Treatment Sequence 5; Treatment Sequence 6

500 mg CK-2017357 DRUG

500 mg CK-2017357 in capsules administered as a single oral dose.

Also known as: tirasemtiv

Treatment Sequence 1; Treatment Sequence 2; Treatment Sequence 3; Treatment Sequence 4; Treatment Sequence 5; Treatment Sequence 6

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• For enrollment, patients were required to satisfy all of the following criteria at baseline:
• \. Able to comprehend and willing to sign an Informed Consent Form (ICF)
• 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) (Brooks, Miller et al. 2000)
• Males or females 18 years of age or older
• Body Mass Index (BMI) of 18.0 to 30.0 kg/m2, inclusive
• Maximum voluntary grip strength in at least one hand between 10 and 40 pounds (females) or 10 and 60 pounds (males)
• Able to swallow capsules with water
• Upright Slow Vital Capacity (SVC) \> 40% of predicted for age, height, and sex \[See Appendix 16.6.1\]
• Able to perform pulmonary function tests
• Pre-study clinical laboratory findings (including troponin I \[TnI\] and creatine phosphokinase \[CPK\]) within normal range, or, if outside of the normal range, deemed not clinically significant by the Investigator
• For female patients only: The patient is post-menopausal (≥ 1 year) or sterilized, or if she is of childbearing potential, she is not breastfeeding, her pregnancy test is negative, she has no intention to become pregnant during the course of the study, and she is using contraceptive drugs or devices for the duration of the study and for 10 weeks after the end of the study.
• For male patients only: Male patients agree for the duration of the study and 10 weeks after the end of the study to use a condom during sexual intercourse with female partners who are of reproductive potential and to have female partners use an additional effective means of contraception (e.g., diaphragm plus spermicide or oral contraceptives) or the male patient must agree to abstain from sexual intercourse for 10 weeks after the end of the study.

You may not qualify if:

• Patients satisfying any of the following criteria at baseline were excluded from enrollment:
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 3 times the upper limit of normal (ULN)
• Life expectancy \< 3 months
• Participation in any trial in which receipt of investigational study drug occurred within 30 days prior to dosing
• Any prior treatment with CK-2017357
• In the opinion of the Investigator, the patient is not suitable to participate in the study

Sponsors & Collaborators

• Cytokinetics: lead

Study Sites (15)

Phoenix Neurological Associates, Ltd.

Phoenix, Arizona, 85018, United States

Location

University Neurology Associates

Fresno, California, 93701, United States

Location

California Pacific Medical Center

San Francisco, California, 94115, United States

Location

Mayo Clinic Florida

Jacksonville, Florida, 32224, United States

Location

University of Kentucky

Lexington, Kentucky, 40536, United States

Location

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

SUNY Upstate Medical Center

Syracuse, New York, 13210, United States

Location

Duke University

Durham, North Carolina, 27705, United States

Location

Providence ALS Center

Portland, Oregon, 97213, United States

Location

Drexel University College of Medicine, Dept of Neurology

Philadelphia, Pennsylvania, 19102, United States

Location

Penn State

University Park, Pennsylvania, 17033, United States

Location

The University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

Location

University of Vermont

Burlington, Vermont, 05401, United States

Location

Related Publications (1)

• Shefner J, Cedarbaum JM, Cudkowicz ME, Maragakis N, Lee J, Jones D, Watson ML, Mahoney K, Chen M, Saikali K, Mao J, Russell AJ, Hansen RL, Malik F, Wolff AA; Neals/Cytokinetics Study Team. Safety, tolerability and pharmacodynamics of a skeletal muscle activator in amyotrophic lateral sclerosis. Amyotroph Lateral Scler. 2012 Sep;13(5):430-8. doi: 10.3109/17482968.2012.684214. Epub 2012 May 16.

  PMID: 22591195 RESULT

Related Links

• Safety, tolerability and pharmacodynamics of a skeletal muscle activator in amyotrophic lateral sclerosis.

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Interventions

CK-2017357

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Jeremy M Shefner, MD, PhD

  State University of New York - Upstate Medical University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 16, 2010
• First Posted: March 18, 2010
• Study Start: March 1, 2010
• Primary Completion: November 1, 2010
• Study Completion: November 1, 2010
• Last Updated: May 10, 2019

Record last verified: 2019-05

Locations

US (15)