NCT01268280

Brief Summary

The primary objective of this early-stage clinical study is to demonstrate an effect of single doses of CK-2017357 on measures of skeletal muscle function and fatigability in patients with generalized myasthenia gravis (MG).

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
32

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Dec 2010

Geographic Reach
1 country

15 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

December 1, 2010

Completed
27 days until next milestone

First Submitted

Initial submission to the registry

December 28, 2010

Completed
2 days until next milestone

First Posted

Study publicly available on registry

December 30, 2010

Completed
1.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2012

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2012

Completed
Last Updated

September 24, 2019

Status Verified

September 1, 2019

Enrollment Period

1.8 years

First QC Date

December 28, 2010

Last Update Submit

September 18, 2019

Conditions

Outcome Measures

Primary Outcomes (3)

  • Quantitative Myasthenia Gravis score (QMG)

    A quantitative motor assessment of muscular weakness on a scale of 0 to 3 with 0 representing "none" and 3 representing "severe". Muscular assessments included in the overall score are effects on double vision, ptosis, facial muscles, swallowing, speech, outstretched arms and legs, forced vital capacity, hand grip strength, and ability to lift head.

    1 day

  • Pulmonary Function Test (VC in liters)

    Forced Vital Capacity

    1 day

  • Manual Muscle Test (MMT)

    Sum of strength or function values assessed by physician on the neck, shoulder, hip and ankle

    1 day

Secondary Outcomes (7)

  • Characterize dose and plasma concentrations of CK-2017357 and QMG

    2 days

  • Characterize dose and plasma concentrations of CK-2017357 and Forced Vital Capacity (FVC)

    2 days

  • Characterize dose and plasma concentrations of CK-2017357 and Manual Muscle Test (MMT)

    2 days

  • Number of patients with adverse events

    4 weeks

  • Modified MG Symptom Score

    2 days

  • +2 more secondary outcomes

Study Arms (6)

Treatment Sequence 1

EXPERIMENTAL

Dosing Period 1 Placebo; Dosing Period 2 CK-2017357 250 mg; Dosing Period 3 CK-2017357 500 mg

Drug: PlaceboDrug: 250 mg CK-2017357Drug: 500 mg CK-2017357

Treatment Sequence 2

EXPERIMENTAL

Dosing Period 1 Placebo; Dosing Period 2 CK-2017357 500 mg; Dosing Period 3 CK-2017357 250 mg

Drug: PlaceboDrug: 250 mg CK-2017357Drug: 500 mg CK-2017357

Treatment Sequence 3

EXPERIMENTAL

Dosing Period 1 CK-2017357 250 mg; Dosing Period 2 Placebo; Dosing Period 3 CK-2017357 500 mg

Drug: PlaceboDrug: 250 mg CK-2017357Drug: 500 mg CK-2017357

Treatment Sequence 4

EXPERIMENTAL

Dosing Period 1 CK-2017357 250 mg; Dosing Period 2 CK-2017357 500 mg; Dosing Period 3 Placebo

Drug: PlaceboDrug: 250 mg CK-2017357Drug: 500 mg CK-2017357

Treatment Sequence 5

EXPERIMENTAL

Dosing Period 1 CK-2017357 500 mg; Dosing Period 2 Placebo; Dosing Period 3 CK-2017357 250 mg

Drug: PlaceboDrug: 250 mg CK-2017357Drug: 500 mg CK-2017357

Treatment Sequence 6

EXPERIMENTAL

Dosing Period 1 CK-2017357 500 mg; Dosing Period 2 CK-2017357 250 mg; Dosing Period 3 Placebo

Drug: PlaceboDrug: 250 mg CK-2017357Drug: 500 mg CK-2017357

Interventions

Matching placebo in capsules administered as a single oral dose.

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

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

Also known as: tirasemtiv
Treatment Sequence 1Treatment Sequence 2Treatment Sequence 3Treatment Sequence 4Treatment Sequence 5Treatment Sequence 6

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

Also known as: tirasemitiv
Treatment Sequence 1Treatment Sequence 2Treatment Sequence 3Treatment Sequence 4Treatment Sequence 5Treatment Sequence 6

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Ability to comprehend and willing to sign an Informed Consent Form (ICF)
  • Ability to understand written and oral English language
  • Males and females between 18 and 80 years of age, inclusive
  • Patient's signs and symptoms not better explained by another disease process
  • Established diagnosis of MG defined as clinical evidence of muscle weakness and positive AChR-binding antibody titer (\>0.02 nmol/L)
  • Myasthenia Gravis Foundation of America (MGFA) clinical classification II or III
  • Stable MG disease for 4 weeks prior to randomization
  • Ability to refrain from IVIg treatments during the course of the study
  • Ability to refrain from cholinesterase-inhibitors (e.g. pyridostigmine) for 12 hours before each dose
  • Ability to perform all elements of the QMG
  • Grade of 2 or 3 in two or more of the following muscle groups as measured by QMG: right or left arm flexion, head lift, and right or left leg raise at 45° Note: Patients may re-screen if they fail due to inadequate weakness from taking pyridostigmine within 12 hours of screening
  • Body mass index (BMI) of 18.0 to 36.0 kg/m2, inclusive
  • Pre-study clinical laboratory findings (including troponin I \[TnI\] and creatine phosphokinase \[CPK\]) within the normal range, or if outside of the normal range, deemed not clinically significant by the Investigator
  • For female patients only: Agreement to use a double barrier during sexual intercourse (1 hormonal, plus 1 barrier method, or 2 simultaneous barrier methods) birth control (birth control pills, male condom, female condom, intrauterine device, Norplant, tubal ligation, or other sterilization procedures)
  • For male patients only: Agreement either 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) for the duration of the study and 10 weeks after the end of the study or to abstain from sexual intercourse for the duration of the study and 10 weeks after the end of the study

You may not qualify if:

  • History of chronic degenerative, psychiatric, or neurologic disorder other than MG that can produce weakness or fatigue
  • Other major chronic or debilitating illnesses within six months prior to study entry
  • Hepatic insufficiency (defined as ALT or AST \> 3x ULN, or total bilirubin \> 3 mg/dL)
  • Renal insufficiency (defined as serum creatinine \> 2.5 mg/dL or receiving dialysis)
  • Other myasthenic syndromes (e.g. Lambert Eaton syndrome; inherited myasthenic syndrome)
  • Female patients who are premenopausal and are: (a) pregnant on the basis of a serum pregnancy test, (b) breast-feeding, or (c) not using an effective method of double barrier (1 hormonal plus 1 barrier method or 2 simultaneous barrier methods) birth control (birth control pills, male condom, female condom, intrauterine device, Norplant, tubal ligation, or other sterilization procedures)
  • Receipt of IVIg or plasmapheresis treatment within 6 weeks prior to the first dose of study drug
  • Changes to immunosuppressive treatments (i.e., prednisone) within 6 weeks prior to the first dose of study drug
  • Rituxan treatment within 3 months prior to study entry
  • Participation in any other investigational study drug or device trial in which receipt of an investigational study drug or device occurred within 30 days prior to dosing
  • Any prior treatment with CK-2017357
  • Recent history of alcoholism or drug abuse, or significant behavioral or psychiatric problems, or other conditions which in the Investigator's opinion may impair ability to adequately comply with the requirements of the study

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (15)

UCSF - Fresno

Fresno, California, 93721, United States

Location

University of California - Irvine

Orange, California, 92868, United States

Location

California Pacific Medical Center

San Francisco, California, 94115, United States

Location

Stanford University

Stanford, California, 94305, United States

Location

Hospital for Special Care

New Britain, Connecticut, 06053, United States

Location

The University of Kansas Medical Center

Kansas City, Kansas, 26506, United States

Location

Johns Hopkins

Baltimore, Maryland, 21205, United States

Location

Neurocare Center for Research

Newton, Massachusetts, 02459, United States

Location

University of North Carolina

Chapel Hill, North Carolina, 27599, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

Drexel University College of Medicine

Philadelphia, Pennsylvania, 19107, United States

Location

West Penn Allegheny Health System

Pittsburgh, Pennsylvania, 15212, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

University of Texas Health Science Center

San Antonio, Texas, 78229, United States

Location

University of Virginia Health System

Charlottesville, Virginia, 22908, United States

Location

Related Publications (1)

  • Sanders DB, Rosenfeld J, Dimachkie M, Meng L, Malik FI. A Study to Evaluate Efficacy, Safety and Tolerability of Single Doses of Tirasemtiv in Patients with Myasthenia Gravis. 65th Annual Meeting of the American Academy of Neurology, San Diego, CA, March 2013

    RESULT

MeSH Terms

Conditions

Myasthenia Gravis

Interventions

CK-2017357

Condition Hierarchy (Ancestors)

Paraneoplastic Syndromes, Nervous SystemNervous System NeoplasmsNeoplasms by SiteNeoplasmsParaneoplastic SyndromesAutoimmune Diseases of the Nervous SystemNervous System DiseasesNeurodegenerative DiseasesNeuromuscular Junction DiseasesNeuromuscular DiseasesAutoimmune DiseasesImmune System Diseases

Study Officials

  • Andrew Wolff, MD, FACC

    Cytokinetics, Inc.

    STUDY DIRECTOR

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

December 28, 2010

First Posted

December 30, 2010

Study Start

December 1, 2010

Primary Completion

October 1, 2012

Study Completion

October 1, 2012

Last Updated

September 24, 2019

Record last verified: 2019-09

Locations