A Study of CK-2017357 in Patients With Amyotrophic Lateral Sclerosis (ALS)
7. mai 2019 oppdatert av: 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.
Studieoversikt
Status
Fullført
Forhold
Intervensjon / Behandling
Detaljert beskrivelse
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.
Studietype
Intervensjonell
Registrering (Faktiske)
67
Fase
- Fase 2
Kontakter og plasseringer
Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.
Studiesteder
-
-
Arizona
-
Phoenix, Arizona, Forente stater, 85018
- Phoenix Neurological Associates, Ltd.
-
-
California
-
Fresno, California, Forente stater, 93701
- University Neurology Associates
-
San Francisco, California, Forente stater, 94115
- California Pacific Medical Center
-
-
Florida
-
Jacksonville, Florida, Forente stater, 32224
- Mayo Clinic Florida
-
-
Kentucky
-
Lexington, Kentucky, Forente stater, 40536
- University of Kentucky
-
-
Maryland
-
Baltimore, Maryland, Forente stater, 21287
- Johns Hopkins Hospital
-
-
Massachusetts
-
Boston, Massachusetts, Forente stater, 02114
- Massachusetts General Hospital
-
-
Missouri
-
Saint Louis, Missouri, Forente stater, 63110
- Washington University
-
-
New York
-
Syracuse, New York, Forente stater, 13210
- SUNY Upstate Medical Center
-
-
North Carolina
-
Durham, North Carolina, Forente stater, 27705
- Duke University
-
-
Oregon
-
Portland, Oregon, Forente stater, 97213
- Providence ALS Center
-
-
Pennsylvania
-
Philadelphia, Pennsylvania, Forente stater, 19102
- Drexel University College of Medicine, Dept of Neurology
-
University Park, Pennsylvania, Forente stater, 17033
- Penn State
-
-
Texas
-
San Antonio, Texas, Forente stater, 78229
- The University of Texas Health Science Center at San Antonio
-
-
Vermont
-
Burlington, Vermont, Forente stater, 05401
- University of Vermont
-
-
Deltakelseskriterier
Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
18 år og eldre (Voksen, Eldre voksen)
Tar imot friske frivillige
Nei
Kjønn som er kvalifisert for studier
Alle
Beskrivelse
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
Studieplan
Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Randomisert
- Intervensjonsmodell: Crossover-oppdrag
- Masking: Firemannsrom
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
|
Eksperimentell: 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.
|
Matchende placebo i kapsler administrert som en enkelt oral dose.
250 mg CK-2017357 i kapsler administrert som en enkelt oral dose.
Andre navn:
500 mg CK-2017357 i kapsler administrert som en enkelt oral dose.
Andre navn:
|
|
Eksperimentell: 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.
|
Matchende placebo i kapsler administrert som en enkelt oral dose.
250 mg CK-2017357 i kapsler administrert som en enkelt oral dose.
Andre navn:
500 mg CK-2017357 i kapsler administrert som en enkelt oral dose.
Andre navn:
|
|
Eksperimentell: 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.
|
Matchende placebo i kapsler administrert som en enkelt oral dose.
250 mg CK-2017357 i kapsler administrert som en enkelt oral dose.
Andre navn:
500 mg CK-2017357 i kapsler administrert som en enkelt oral dose.
Andre navn:
|
|
Eksperimentell: 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.
|
Matchende placebo i kapsler administrert som en enkelt oral dose.
250 mg CK-2017357 i kapsler administrert som en enkelt oral dose.
Andre navn:
500 mg CK-2017357 i kapsler administrert som en enkelt oral dose.
Andre navn:
|
|
Eksperimentell: 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.
|
Matchende placebo i kapsler administrert som en enkelt oral dose.
250 mg CK-2017357 i kapsler administrert som en enkelt oral dose.
Andre navn:
500 mg CK-2017357 i kapsler administrert som en enkelt oral dose.
Andre navn:
|
|
Eksperimentell: 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.
|
Matchende placebo i kapsler administrert som en enkelt oral dose.
250 mg CK-2017357 i kapsler administrert som en enkelt oral dose.
Andre navn:
500 mg CK-2017357 i kapsler administrert som en enkelt oral dose.
Andre navn:
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
ALSFRS-R
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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)
Tidsramme: 2 days
|
SVC is measured using the Puritan Bennett Renaissance II Spirometry System and accessories.
|
2 days
|
|
Maximum Voluntary Ventilation (MVV)
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 2 days
|
MVC is measured using the MicroFET 2 HHD.
|
2 days
|
|
Repeated Sub-Maximum Grip Strength Fatigability
Tidsramme: 2 days
|
Sub-Maximum Grip Strength Fatigability is measured using the DynEx Electronic Hand.
Dynamometer
|
2 days
|
Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Antall pasienter med uønskede hendelser
Tidsramme: 4 uker
|
4 uker
|
|
|
Characterize the relationship, if any, between the plasma concentration of CK-2017357 and ALSFRS-R.
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
|
Samarbeidspartnere og etterforskere
Det er her du vil finne personer og organisasjoner som er involvert i denne studien.
Sponsor
Etterforskere
- Studiestol: Jeremy M Shefner, MD, PhD, State University of New York - Upstate Medical University
Publikasjoner og nyttige lenker
Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.
Studierekorddatoer
Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.
Studer hoveddatoer
Studiestart
1. mars 2010
Primær fullføring (Faktiske)
1. november 2010
Studiet fullført (Faktiske)
1. november 2010
Datoer for studieregistrering
Først innsendt
16. mars 2010
Først innsendt som oppfylte QC-kriteriene
17. mars 2010
Først lagt ut (Anslag)
18. mars 2010
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
10. mai 2019
Siste oppdatering sendt inn som oppfylte QC-kriteriene
7. mai 2019
Sist bekreftet
1. mai 2019
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- CY 4021
Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .