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

7 mai 2019 mis à jour par: 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.

Aperçu de l'étude

Statut

Complété

Les conditions

Intervention / Traitement

Description détaillée

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.

Type d'étude

Interventionnel

Inscription (Réel)

67

Phase

  • Phase 2

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

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

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans et plus (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

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 d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: Randomisé
  • Modèle interventionnel: Affectation croisée
  • Masquage: Quadruple

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: 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.
Médicament: Placebo
Un placebo correspondant sous forme de gélules administrées en une seule dose orale.
Médicament: 250mgCK-2017357
250 mg de CK-2017357 en gélules administrées en une dose orale unique.
Autres noms:
  • tirasemtiv
Médicament: 500mgCK-2017357
500 mg de CK-2017357 en gélules administrées en une dose orale unique.
Autres noms:
  • tirasemtiv
Expérimental: 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.
Médicament: Placebo
Un placebo correspondant sous forme de gélules administrées en une seule dose orale.
Médicament: 250mgCK-2017357
250 mg de CK-2017357 en gélules administrées en une dose orale unique.
Autres noms:
  • tirasemtiv
Médicament: 500mgCK-2017357
500 mg de CK-2017357 en gélules administrées en une dose orale unique.
Autres noms:
  • tirasemtiv
Expérimental: 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.
Médicament: Placebo
Un placebo correspondant sous forme de gélules administrées en une seule dose orale.
Médicament: 250mgCK-2017357
250 mg de CK-2017357 en gélules administrées en une dose orale unique.
Autres noms:
  • tirasemtiv
Médicament: 500mgCK-2017357
500 mg de CK-2017357 en gélules administrées en une dose orale unique.
Autres noms:
  • tirasemtiv
Expérimental: 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.
Médicament: Placebo
Un placebo correspondant sous forme de gélules administrées en une seule dose orale.
Médicament: 250mgCK-2017357
250 mg de CK-2017357 en gélules administrées en une dose orale unique.
Autres noms:
  • tirasemtiv
Médicament: 500mgCK-2017357
500 mg de CK-2017357 en gélules administrées en une dose orale unique.
Autres noms:
  • tirasemtiv
Expérimental: 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.
Médicament: Placebo
Un placebo correspondant sous forme de gélules administrées en une seule dose orale.
Médicament: 250mgCK-2017357
250 mg de CK-2017357 en gélules administrées en une dose orale unique.
Autres noms:
  • tirasemtiv
Médicament: 500mgCK-2017357
500 mg de CK-2017357 en gélules administrées en une dose orale unique.
Autres noms:
  • tirasemtiv
Expérimental: 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.
Médicament: Placebo
Un placebo correspondant sous forme de gélules administrées en une seule dose orale.
Médicament: 250mgCK-2017357
250 mg de CK-2017357 en gélules administrées en une dose orale unique.
Autres noms:
  • tirasemtiv
Médicament: 500mgCK-2017357
500 mg de CK-2017357 en gélules administrées en une dose orale unique.
Autres noms:
  • tirasemtiv

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
ALSFRS-R
Délai: 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
Délai: 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
Délai: 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
Délai: 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)
Délai: 2 days
SVC is measured using the Puritan Bennett Renaissance II Spirometry System and accessories.
2 days
Maximum Voluntary Ventilation (MVV)
Délai: 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)
Délai: 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)
Délai: 2 days
MVC is measured using the MicroFET 2 HHD.
2 days
Repeated Sub-Maximum Grip Strength Fatigability
Délai: 2 days
Sub-Maximum Grip Strength Fatigability is measured using the DynEx Electronic Hand. Dynamometer
2 days

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Nombre de patients présentant des événements indésirables
Délai: 4 semaines
4 semaines
Characterize the relationship, if any, between the plasma concentration of CK-2017357 and ALSFRS-R.
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Cytokinetics

Les enquêteurs

  • Chaise d'étude: Jeremy M Shefner, MD, PhD, State University of New York - Upstate Medical University

Publications et liens utiles

La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.

Publications générales

Liens utiles

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude

1 mars 2010

Achèvement primaire (Réel)

1 novembre 2010

Achèvement de l'étude (Réel)

1 novembre 2010

Dates d'inscription aux études

Première soumission

16 mars 2010

Première soumission répondant aux critères de contrôle qualité

17 mars 2010

Première publication (Estimation)

18 mars 2010

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

10 mai 2019

Dernière mise à jour soumise répondant aux critères de contrôle qualité

7 mai 2019

Dernière vérification

1 mai 2019

Plus d'information

Termes liés à cette étude

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • CY 4021

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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