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

7. Mai 2019 aktualisiert von: 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.

Studienübersicht

Status

Abgeschlossen

Bedingungen

Intervention / Behandlung

Detaillierte Beschreibung

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.

Studientyp

Interventionell

Einschreibung (Tatsächlich)

67

Phase

  • Phase 2

Kontakte und Standorte

Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.

Studienorte

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

Teilnahmekriterien

Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.

Zulassungskriterien

Studienberechtigtes Alter

18 Jahre und älter (Erwachsene, Älterer Erwachsener)

Akzeptiert gesunde Freiwillige

Nein

Studienberechtigte Geschlechter

Alle

Beschreibung

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

Studienplan

Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.

Wie ist die Studie aufgebaut?

Designdetails

  • Hauptzweck: Behandlung
  • Zuteilung: Zufällig
  • Interventionsmodell: Crossover-Aufgabe
  • Maskierung: Vervierfachen

Waffen und Interventionen

Teilnehmergruppe / Arm
Intervention / Behandlung
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.
Arzneimittel: Placebo
Passendes Placebo in Kapseln, verabreicht als orale Einzeldosis.
Arzneimittel: 250 mg CK-2017357
250 mg CK-2017357 in Kapseln, verabreicht als orale Einzeldosis.
Andere Namen:
  • tirasemtiv
Arzneimittel: 500 mg CK-2017357
500 mg CK-2017357 in Kapseln, verabreicht als orale Einzeldosis.
Andere Namen:
  • 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.
Arzneimittel: Placebo
Passendes Placebo in Kapseln, verabreicht als orale Einzeldosis.
Arzneimittel: 250 mg CK-2017357
250 mg CK-2017357 in Kapseln, verabreicht als orale Einzeldosis.
Andere Namen:
  • tirasemtiv
Arzneimittel: 500 mg CK-2017357
500 mg CK-2017357 in Kapseln, verabreicht als orale Einzeldosis.
Andere Namen:
  • 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.
Arzneimittel: Placebo
Passendes Placebo in Kapseln, verabreicht als orale Einzeldosis.
Arzneimittel: 250 mg CK-2017357
250 mg CK-2017357 in Kapseln, verabreicht als orale Einzeldosis.
Andere Namen:
  • tirasemtiv
Arzneimittel: 500 mg CK-2017357
500 mg CK-2017357 in Kapseln, verabreicht als orale Einzeldosis.
Andere Namen:
  • 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.
Arzneimittel: Placebo
Passendes Placebo in Kapseln, verabreicht als orale Einzeldosis.
Arzneimittel: 250 mg CK-2017357
250 mg CK-2017357 in Kapseln, verabreicht als orale Einzeldosis.
Andere Namen:
  • tirasemtiv
Arzneimittel: 500 mg CK-2017357
500 mg CK-2017357 in Kapseln, verabreicht als orale Einzeldosis.
Andere Namen:
  • 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.
Arzneimittel: Placebo
Passendes Placebo in Kapseln, verabreicht als orale Einzeldosis.
Arzneimittel: 250 mg CK-2017357
250 mg CK-2017357 in Kapseln, verabreicht als orale Einzeldosis.
Andere Namen:
  • tirasemtiv
Arzneimittel: 500 mg CK-2017357
500 mg CK-2017357 in Kapseln, verabreicht als orale Einzeldosis.
Andere Namen:
  • 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.
Arzneimittel: Placebo
Passendes Placebo in Kapseln, verabreicht als orale Einzeldosis.
Arzneimittel: 250 mg CK-2017357
250 mg CK-2017357 in Kapseln, verabreicht als orale Einzeldosis.
Andere Namen:
  • tirasemtiv
Arzneimittel: 500 mg CK-2017357
500 mg CK-2017357 in Kapseln, verabreicht als orale Einzeldosis.
Andere Namen:
  • tirasemtiv

Was misst die Studie?

Primäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
ALSFRS-R
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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)
Zeitfenster: 2 days
SVC is measured using the Puritan Bennett Renaissance II Spirometry System and accessories.
2 days
Maximum Voluntary Ventilation (MVV)
Zeitfenster: 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)
Zeitfenster: 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)
Zeitfenster: 2 days
MVC is measured using the MicroFET 2 HHD.
2 days
Repeated Sub-Maximum Grip Strength Fatigability
Zeitfenster: 2 days
Sub-Maximum Grip Strength Fatigability is measured using the DynEx Electronic Hand. Dynamometer
2 days

Sekundäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Anzahl der Patienten mit unerwünschten Ereignissen
Zeitfenster: 4 Wochen
4 Wochen
Characterize the relationship, if any, between the plasma concentration of CK-2017357 and ALSFRS-R.
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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

Mitarbeiter und Ermittler

Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.

Sponsor

Cytokinetics

Ermittler

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

Publikationen und hilfreiche Links

Die Bereitstellung dieser Publikationen erfolgt freiwillig durch die für die Eingabe von Informationen über die Studie verantwortliche Person. Diese können sich auf alles beziehen, was mit dem Studium zu tun hat.

Allgemeine Veröffentlichungen

Nützliche Links

Studienaufzeichnungsdaten

Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.

Haupttermine studieren

Studienbeginn

1. März 2010

Primärer Abschluss (Tatsächlich)

1. November 2010

Studienabschluss (Tatsächlich)

1. November 2010

Studienanmeldedaten

Zuerst eingereicht

16. März 2010

Zuerst eingereicht, das die QC-Kriterien erfüllt hat

17. März 2010

Zuerst gepostet (Schätzen)

18. März 2010

Studienaufzeichnungsaktualisierungen

Letztes Update gepostet (Tatsächlich)

10. Mai 2019

Letztes eingereichtes Update, das die QC-Kriterien erfüllt

7. Mai 2019

Zuletzt verifiziert

1. Mai 2019

Mehr Informationen

Begriffe im Zusammenhang mit dieser Studie

Zusätzliche relevante MeSH-Bedingungen

Andere Studien-ID-Nummern

  • CY 4021

Diese Informationen wurden ohne Änderungen direkt von der Website clinicaltrials.gov abgerufen. Wenn Sie Ihre Studiendaten ändern, entfernen oder aktualisieren möchten, wenden Sie sich bitte an register@clinicaltrials.gov. Sobald eine Änderung auf clinicaltrials.gov implementiert wird, wird diese automatisch auch auf unserer Website aktualisiert .

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