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

7 de mayo de 2019 actualizado por: Cytokinetics

A Phase II, Double-Blind, Randomized, Placebo-Controlled, Three-Way Crossover, Pharmacokinetic and Pharmacodynamic Study of CK-2017357 in Patients With Amyotrophic Lateral Sclerosis (ALS)

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.

Descripción general del estudio

Estado

Terminado

Condiciones

Intervención / Tratamiento

Descripción detallada

This study is a Phase II, double-blind, randomized, placebo-controlled, three-way crossover study of CK-2017357 in patients with ALS. 36 to 72 patients will be randomized to one of six different treatment sequences. Each treatment sequence consists of three dosing periods; in each dosing period¸ patients receive a single oral dose of placebo, 250 mg of CK-2017357, or 500 mg of CK-2017357. All six treatment sequences will enroll approximately the same number of patients. A washout period of at least 6 days (to a maximum of 10 days) will be employed between the doses for each patient. This study is designed to assess the effect of CK-2017357 on maximal voluntary muscle strength, on the development of fatigue at maximal and sub-maximal voluntary muscle contraction, and on selected pulmonary function parameters. The plasma concentration of CK-2017357 will be measured at selected time points after each of two single doses of CK-2017357 in men and women. The plasma concentration versus time data obtained in this study may be used to develop a population PK model and estimate inter-subject variability of PK parameters in this target patient population, in particular between male and female study patients.

Tipo de estudio

Intervencionista

Inscripción (Actual)

67

Fase

  • Fase 2

Contactos y Ubicaciones

Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.

Ubicaciones de estudio

  • Estados Unidos
    • Arizona
      • Phoenix, Arizona, Estados Unidos, 85018
        • Phoenix Neurological Associates, Ltd.
    • California
      • Fresno, California, Estados Unidos, 93701
        • University Neurology Associates
      • San Francisco, California, Estados Unidos, 94115
        • California Pacific Medical Center
    • Florida
      • Jacksonville, Florida, Estados Unidos, 32224
        • Mayo Clinic Florida
    • Kentucky
      • Lexington, Kentucky, Estados Unidos, 40536
        • University of Kentucky
    • Maryland
      • Baltimore, Maryland, Estados Unidos, 21287
        • Johns Hopkins Hospital
    • Massachusetts
      • Boston, Massachusetts, Estados Unidos, 02114
        • Massachusetts General Hospital
    • Missouri
      • Saint Louis, Missouri, Estados Unidos, 63110
        • Washington University
    • New York
      • Syracuse, New York, Estados Unidos, 13210
        • SUNY Upstate Medical Center
    • North Carolina
      • Durham, North Carolina, Estados Unidos, 27705
        • Duke University
    • Oregon
      • Portland, Oregon, Estados Unidos, 97213
        • Providence ALS Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, Estados Unidos, 19102
        • Drexel University College of Medicine, Dept of Neurology
      • University Park, Pennsylvania, Estados Unidos, 17033
        • Penn State
    • Texas
      • San Antonio, Texas, Estados Unidos, 78229
        • The University of Texas Health Science Center at San Antonio
    • Vermont
      • Burlington, Vermont, Estados Unidos, 05401
        • University of Vermont

Criterios de participación

Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.

Criterio de elegibilidad

Edades elegibles para estudiar

18 años y mayores (Adulto, Adulto Mayor)

Acepta Voluntarios Saludables

No

Géneros elegibles para el estudio

Todos

Descripción

Inclusion Criteria

For enrollment, patients were required to satisfy all of the following criteria at baseline:

1. Able to comprehend and willing to sign an Informed Consent Form (ICF)

  1. 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)
  2. Males or females 18 years of age or older
  3. Body Mass Index (BMI) of 18.0 to 30.0 kg/m2, inclusive
  4. Maximum voluntary grip strength in at least one hand between 10 and 40 pounds (females) or 10 and 60 pounds (males)
  5. Able to swallow capsules with water
  6. Upright Slow Vital Capacity (SVC) > 40% of predicted for age, height, and sex [See Appendix 16.6.1]
  7. Able to perform pulmonary function tests
  8. 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
  9. 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.

Exclusion Criteria

Patients satisfying any of the following criteria at baseline were excluded from enrollment:

  1. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3 times the upper limit of normal (ULN)
  2. Life expectancy < 3 months
  3. Participation in any trial in which receipt of investigational study drug occurred within 30 days prior to dosing
  4. Any prior treatment with CK-2017357
  5. In the opinion of the Investigator, the patient is not suitable to participate in the study

Plan de estudios

Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.

¿Cómo está diseñado el estudio?

Detalles de diseño

  • Propósito principal: Tratamiento
  • Asignación: Aleatorizado
  • Modelo Intervencionista: Asignación cruzada
  • Enmascaramiento: Cuadruplicar

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Experimental: Treatment Sequence 1
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.
Droga: Placebo
Placebo de combinación en cápsulas administradas como dosis oral única.
Droga: 250 mg CK-2017357
250 mg de CK-2017357 en cápsulas administradas como dosis única oral.
Otros nombres:
  • tirasemtiv
Droga: 500 mg CK-2017357
500 mg de CK-2017357 en cápsulas administradas como dosis única oral.
Otros nombres:
  • tirasemtiv
Experimental: Treatment Sequence 2
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.
Droga: Placebo
Placebo de combinación en cápsulas administradas como dosis oral única.
Droga: 250 mg CK-2017357
250 mg de CK-2017357 en cápsulas administradas como dosis única oral.
Otros nombres:
  • tirasemtiv
Droga: 500 mg CK-2017357
500 mg de CK-2017357 en cápsulas administradas como dosis única oral.
Otros nombres:
  • tirasemtiv
Experimental: Treatment Sequence 3
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.
Droga: Placebo
Placebo de combinación en cápsulas administradas como dosis oral única.
Droga: 250 mg CK-2017357
250 mg de CK-2017357 en cápsulas administradas como dosis única oral.
Otros nombres:
  • tirasemtiv
Droga: 500 mg CK-2017357
500 mg de CK-2017357 en cápsulas administradas como dosis única oral.
Otros nombres:
  • tirasemtiv
Experimental: Treatment Sequence 4
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.
Droga: Placebo
Placebo de combinación en cápsulas administradas como dosis oral única.
Droga: 250 mg CK-2017357
250 mg de CK-2017357 en cápsulas administradas como dosis única oral.
Otros nombres:
  • tirasemtiv
Droga: 500 mg CK-2017357
500 mg de CK-2017357 en cápsulas administradas como dosis única oral.
Otros nombres:
  • tirasemtiv
Experimental: Treatment Sequence 5
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.
Droga: Placebo
Placebo de combinación en cápsulas administradas como dosis oral única.
Droga: 250 mg CK-2017357
250 mg de CK-2017357 en cápsulas administradas como dosis única oral.
Otros nombres:
  • tirasemtiv
Droga: 500 mg CK-2017357
500 mg de CK-2017357 en cápsulas administradas como dosis única oral.
Otros nombres:
  • tirasemtiv
Experimental: Treatment Sequence 6
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.
Droga: Placebo
Placebo de combinación en cápsulas administradas como dosis oral única.
Droga: 250 mg CK-2017357
250 mg de CK-2017357 en cápsulas administradas como dosis única oral.
Otros nombres:
  • tirasemtiv
Droga: 500 mg CK-2017357
500 mg de CK-2017357 en cápsulas administradas como dosis única oral.
Otros nombres:
  • tirasemtiv

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
ALSFRS-R
Periodo de tiempo: 2 days
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
Periodo de tiempo: 2 days
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
Periodo de tiempo: 2 days
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
Periodo de tiempo: 2 days
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)
Periodo de tiempo: 2 days
SVC is measured using the Puritan Bennett Renaissance II Spirometry System and accessories.
2 days
Maximum Voluntary Ventilation (MVV)
Periodo de tiempo: 2 days
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)
Periodo de tiempo: 2 days
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)
Periodo de tiempo: 2 days
MVC is measured using the MicroFET 2 HHD.
2 days
Repeated Sub-Maximum Grip Strength Fatigability
Periodo de tiempo: 2 days
Sub-Maximum Grip Strength Fatigability is measured using the DynEx Electronic Hand. Dynamometer
2 days

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Número de pacientes con eventos adversos
Periodo de tiempo: 4 semanas
4 semanas
Characterize the relationship, if any, between the plasma concentration of CK-2017357 and ALSFRS-R.
Periodo de tiempo: 2 days
ALSFRS-R assessments will be paired with PK concentrations obtained at or near the same time as the ALSFRS-R assessments and analyzed for concentration related effects.
2 days
Characterize the relationship, if any, between the plasma concentration of CK-2017357 and maximum grip strength
Periodo de tiempo: 2 days
Maximum grip strength assessments will be paired with PK concentrations obtained at or near the same time as the maximum grip strength assessments and analyzed for concentration related effects.
2 days
Characterize the relationship, if any, between the plasma concentration of CK-2017357 and maximum grip strength fatigability
Periodo de tiempo: 2 days
Maximum grip strength fatigability assessments will be paired with PK concentrations obtained at or near the same time as the maximum grip strength fatigability assessments and analyzed for concentration related effects.
2 days
Characterize the relationship, if any, between the plasma concentration of CK-2017357 and shoulder extension fatigue
Periodo de tiempo: 2 days
Shoulder extension fatigue assessments will be paired with PK concentrations obtained at or near the same time as the shoulder extension fatigue assessments and analyzed for concentration related effects.
2 days
Characterize the relationship, if any, between the plasma concentration of CK-2017357 and slow vital capacity
Periodo de tiempo: 2 days
Slow vital capacity assessments will be paired with PK concentrations obtained at or near the same time as the slow vital capacity assessments and analyzed for concentration related effects.
2 days
Characterize the relationship, if any, between the plasma concentration of CK-2017357 and maximum voluntary ventilation
Periodo de tiempo: 2 days
Maximum voluntary ventilation assessments will be paired with PK concentrations obtained at or near the same time as the maximum voluntary ventilation assessments and analyzed for concentration related effects.
2 days
Characterize the relationship, if any, between the plasma concentration of CK-2017357 and sniff inspiratory pressure
Periodo de tiempo: 2 days
Sniff inspiratory pressure assessments will be paired with PK concentrations obtained at or near the same time as the sniff inspiratory pressure assessments and analyzed for concentration related effects.
2 days
Characterize the relationship, if any, between the plasma concentration of CK-2017357 and maximum voluntary muscle contraction
Periodo de tiempo: 2 days
Maximum voluntary muscle contraction assessments will be paired with PK concentrations obtained at or near the same time as the maximum voluntary muscle contraction assessments and analyzed for concentration related effects.
2 days
Characterize the relationship, if any, between the plasma concentration of CK-2017357 and repeated sub-maximum grip strength fatigability
Periodo de tiempo: 2 days
Repeated sub-maximum grip strength fatigability assessments will be paired with PK concentrations obtained at or near the same time as the repeated sub-maximum grip strength fatigability assessments and analyzed for concentration related effects.
2 days
Effect of CK-2017357 on patient determined global functional assessment
Periodo de tiempo: 2 days
Patients will be asked to assess whether they feel the same, better or worse as compared to how they felt pre-dose
2 days
Effect of CK-2017357 on investigator determined global functional assessment
Periodo de tiempo: 2 days
Investigator will assess whether they the patient appears the same, better or worse as compared to the patient's status at pre-dose
2 days

Colaboradores e Investigadores

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Patrocinador

Cytokinetics

Investigadores

  • Silla de estudio: Jeremy M Shefner, MD, PhD, State University of New York - Upstate Medical University

Publicaciones y enlaces útiles

La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.

Publicaciones Generales

Enlaces Útiles

Fechas de registro del estudio

Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados ​​por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.

Fechas importantes del estudio

Inicio del estudio

1 de marzo de 2010

Finalización primaria (Actual)

1 de noviembre de 2010

Finalización del estudio (Actual)

1 de noviembre de 2010

Fechas de registro del estudio

Enviado por primera vez

16 de marzo de 2010

Primero enviado que cumplió con los criterios de control de calidad

17 de marzo de 2010

Publicado por primera vez (Estimar)

18 de marzo de 2010

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

10 de mayo de 2019

Última actualización enviada que cumplió con los criterios de control de calidad

7 de mayo de 2019

Última verificación

1 de mayo de 2019

Más información

Términos relacionados con este estudio

Términos MeSH relevantes adicionales

Otros números de identificación del estudio

  • CY 4021

Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .

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