A Study of CK-2017357 in Patients With Amyotrophic Lateral Sclerosis (ALS)
tiistai 7. toukokuuta 2019 päivittänyt: 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.
Tutkimuksen yleiskatsaus
Tila
Valmis
Interventio / Hoito
Yksityiskohtainen kuvaus
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.
Opintotyyppi
Interventio
Ilmoittautuminen (Todellinen)
67
Vaihe
- Vaihe 2
Yhteystiedot ja paikat
Tässä osiossa on tutkimuksen suorittajien yhteystiedot ja tiedot siitä, missä tämä tutkimus suoritetaan.
Opiskelupaikat
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Arizona
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Phoenix, Arizona, Yhdysvallat, 85018
- Phoenix Neurological Associates, Ltd.
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California
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Fresno, California, Yhdysvallat, 93701
- University Neurology Associates
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San Francisco, California, Yhdysvallat, 94115
- California Pacific Medical Center
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Florida
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Jacksonville, Florida, Yhdysvallat, 32224
- Mayo Clinic Florida
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Kentucky
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Lexington, Kentucky, Yhdysvallat, 40536
- University of Kentucky
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Maryland
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Baltimore, Maryland, Yhdysvallat, 21287
- Johns Hopkins Hospital
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Massachusetts
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Boston, Massachusetts, Yhdysvallat, 02114
- Massachusetts General Hospital
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Missouri
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Saint Louis, Missouri, Yhdysvallat, 63110
- Washington University
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New York
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Syracuse, New York, Yhdysvallat, 13210
- SUNY Upstate Medical Center
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North Carolina
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Durham, North Carolina, Yhdysvallat, 27705
- Duke University
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Oregon
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Portland, Oregon, Yhdysvallat, 97213
- Providence ALS Center
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Pennsylvania
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Philadelphia, Pennsylvania, Yhdysvallat, 19102
- Drexel University College of Medicine, Dept of Neurology
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University Park, Pennsylvania, Yhdysvallat, 17033
- Penn State
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Texas
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San Antonio, Texas, Yhdysvallat, 78229
- The University of Texas Health Science Center at San Antonio
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Vermont
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Burlington, Vermont, Yhdysvallat, 05401
- University of Vermont
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Osallistumiskriteerit
Tutkijat etsivät ihmisiä, jotka sopivat tiettyyn kuvaukseen, jota kutsutaan kelpoisuuskriteereiksi. Joitakin esimerkkejä näistä kriteereistä ovat henkilön yleinen terveydentila tai aiemmat hoidot.
Kelpoisuusvaatimukset
Opintokelpoiset iät
18 vuotta ja vanhemmat (Aikuinen, Vanhempi Aikuinen)
Hyväksyy terveitä vapaaehtoisia
Ei
Sukupuolet, jotka voivat opiskella
Kaikki
Kuvaus
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)
- 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.
Exclusion Criteria
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
Opintosuunnitelma
Tässä osiossa on tietoja tutkimussuunnitelmasta, mukaan lukien kuinka tutkimus on suunniteltu ja mitä tutkimuksella mitataan.
Miten tutkimus on suunniteltu?
Suunnittelun yksityiskohdat
- Ensisijainen käyttötarkoitus: Hoito
- Jako: Satunnaistettu
- Inventiomalli: Crossover-tehtävä
- Naamiointi: Nelinkertaistaa
Aseet ja interventiot
Osallistujaryhmä / Arm |
Interventio / Hoito |
|---|---|
|
Kokeellinen: 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.
|
Vastaava lumelääke kapseleissa kerta-annoksena suun kautta.
250 mg CK-2017357 kapseleissa kerta-annoksena suun kautta.
Muut nimet:
500 mg CK-2017357 kapseleissa kerta-annoksena suun kautta.
Muut nimet:
|
|
Kokeellinen: 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.
|
Vastaava lumelääke kapseleissa kerta-annoksena suun kautta.
250 mg CK-2017357 kapseleissa kerta-annoksena suun kautta.
Muut nimet:
500 mg CK-2017357 kapseleissa kerta-annoksena suun kautta.
Muut nimet:
|
|
Kokeellinen: 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.
|
Vastaava lumelääke kapseleissa kerta-annoksena suun kautta.
250 mg CK-2017357 kapseleissa kerta-annoksena suun kautta.
Muut nimet:
500 mg CK-2017357 kapseleissa kerta-annoksena suun kautta.
Muut nimet:
|
|
Kokeellinen: 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.
|
Vastaava lumelääke kapseleissa kerta-annoksena suun kautta.
250 mg CK-2017357 kapseleissa kerta-annoksena suun kautta.
Muut nimet:
500 mg CK-2017357 kapseleissa kerta-annoksena suun kautta.
Muut nimet:
|
|
Kokeellinen: 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.
|
Vastaava lumelääke kapseleissa kerta-annoksena suun kautta.
250 mg CK-2017357 kapseleissa kerta-annoksena suun kautta.
Muut nimet:
500 mg CK-2017357 kapseleissa kerta-annoksena suun kautta.
Muut nimet:
|
|
Kokeellinen: 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.
|
Vastaava lumelääke kapseleissa kerta-annoksena suun kautta.
250 mg CK-2017357 kapseleissa kerta-annoksena suun kautta.
Muut nimet:
500 mg CK-2017357 kapseleissa kerta-annoksena suun kautta.
Muut nimet:
|
Mitä tutkimuksessa mitataan?
Ensisijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
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ALSFRS-R
Aikaikkuna: 2 days
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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.
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2 days
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Maximum grip strength
Aikaikkuna: 2 days
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Measured using the DynEx Electronic Hand Dynamometer.
Patients asked to squeeze the device with the maximum possible force to establish the maximum voluntary contraction.
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2 days
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Maximum grip strength fatigability
Aikaikkuna: 2 days
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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.
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2 days
|
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Shoulder extension fatigue
Aikaikkuna: 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.
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2 days
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Slow Vital Capacity (SVC)
Aikaikkuna: 2 days
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SVC is measured using the Puritan Bennett Renaissance II Spirometry System and accessories.
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2 days
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Maximum Voluntary Ventilation (MVV)
Aikaikkuna: 2 days
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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.
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2 days
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Sniff Inspiratory Pressure (SNIP)
Aikaikkuna: 2 days
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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
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2 days
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Maximum Voluntary Muscle Contraction (MVC)
Aikaikkuna: 2 days
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MVC is measured using the MicroFET 2 HHD.
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2 days
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Repeated Sub-Maximum Grip Strength Fatigability
Aikaikkuna: 2 days
|
Sub-Maximum Grip Strength Fatigability is measured using the DynEx Electronic Hand.
Dynamometer
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2 days
|
Toissijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
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Niiden potilaiden määrä, joilla on haittavaikutuksia
Aikaikkuna: 4 viikkoa
|
4 viikkoa
|
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Characterize the relationship, if any, between the plasma concentration of CK-2017357 and ALSFRS-R.
Aikaikkuna: 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.
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2 days
|
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Characterize the relationship, if any, between the plasma concentration of CK-2017357 and maximum grip strength
Aikaikkuna: 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
|
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Characterize the relationship, if any, between the plasma concentration of CK-2017357 and maximum grip strength fatigability
Aikaikkuna: 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
|
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Characterize the relationship, if any, between the plasma concentration of CK-2017357 and shoulder extension fatigue
Aikaikkuna: 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.
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2 days
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Characterize the relationship, if any, between the plasma concentration of CK-2017357 and slow vital capacity
Aikaikkuna: 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.
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2 days
|
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Characterize the relationship, if any, between the plasma concentration of CK-2017357 and maximum voluntary ventilation
Aikaikkuna: 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
|
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Characterize the relationship, if any, between the plasma concentration of CK-2017357 and sniff inspiratory pressure
Aikaikkuna: 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
|
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Characterize the relationship, if any, between the plasma concentration of CK-2017357 and maximum voluntary muscle contraction
Aikaikkuna: 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
|
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Characterize the relationship, if any, between the plasma concentration of CK-2017357 and repeated sub-maximum grip strength fatigability
Aikaikkuna: 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
|
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Effect of CK-2017357 on patient determined global functional assessment
Aikaikkuna: 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
Aikaikkuna: 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
|
Yhteistyökumppanit ja tutkijat
Täältä löydät tähän tutkimukseen osallistuvat ihmiset ja organisaatiot.
Sponsori
Tutkijat
- Opintojen puheenjohtaja: Jeremy M Shefner, MD, PhD, State University of New York - Upstate Medical University
Julkaisuja ja hyödyllisiä linkkejä
Tutkimusta koskevien tietojen syöttämisestä vastaava henkilö toimittaa nämä julkaisut vapaaehtoisesti. Nämä voivat koskea mitä tahansa tutkimukseen liittyvää.
Opintojen ennätyspäivät
Nämä päivämäärät seuraavat ClinicalTrials.gov-sivustolle lähetettyjen tutkimustietueiden ja yhteenvetojen edistymistä. National Library of Medicine (NLM) tarkistaa tutkimustiedot ja raportoidut tulokset varmistaakseen, että ne täyttävät tietyt laadunvalvontastandardit, ennen kuin ne julkaistaan julkisella verkkosivustolla.
Opi tärkeimmät päivämäärät
Opiskelun aloitus
Maanantai 1. maaliskuuta 2010
Ensisijainen valmistuminen (Todellinen)
Maanantai 1. marraskuuta 2010
Opintojen valmistuminen (Todellinen)
Maanantai 1. marraskuuta 2010
Opintoihin ilmoittautumispäivät
Ensimmäinen lähetetty
Tiistai 16. maaliskuuta 2010
Ensimmäinen toimitettu, joka täytti QC-kriteerit
Keskiviikko 17. maaliskuuta 2010
Ensimmäinen Lähetetty (Arvio)
Torstai 18. maaliskuuta 2010
Tutkimustietojen päivitykset
Viimeisin päivitys julkaistu (Todellinen)
Perjantai 10. toukokuuta 2019
Viimeisin lähetetty päivitys, joka täytti QC-kriteerit
Tiistai 7. toukokuuta 2019
Viimeksi vahvistettu
Keskiviikko 1. toukokuuta 2019
Lisää tietoa
Tähän tutkimukseen liittyvät termit
Muita asiaankuuluvia MeSH-ehtoja
Muut tutkimustunnusnumerot
- CY 4021
Nämä tiedot haettiin suoraan verkkosivustolta clinicaltrials.gov ilman muutoksia. Jos sinulla on pyyntöjä muuttaa, poistaa tai päivittää tutkimustietojasi, ota yhteyttä register@clinicaltrials.gov. Heti kun muutos on otettu käyttöön osoitteessa clinicaltrials.gov, se päivitetään automaattisesti myös verkkosivustollemme .