A Study of CK-2017357 in Patients With Amyotrophic Lateral Sclerosis (ALS)
7 de maio de 2019 atualizado 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.
Visão geral do estudo
Status
Concluído
Condições
Intervenção / Tratamento
Descrição detalhada
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 estudo
Intervencional
Inscrição (Real)
67
Estágio
- Fase 2
Contactos e Locais
Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.
Locais de estudo
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Arizona
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Phoenix, Arizona, Estados Unidos, 85018
- Phoenix Neurological Associates, Ltd.
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California
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Fresno, California, Estados Unidos, 93701
- University Neurology Associates
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San Francisco, California, Estados Unidos, 94115
- California Pacific Medical Center
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Florida
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Jacksonville, Florida, Estados Unidos, 32224
- Mayo Clinic Florida
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Kentucky
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Lexington, Kentucky, Estados Unidos, 40536
- University Of Kentucky
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Maryland
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Baltimore, Maryland, Estados Unidos, 21287
- Johns Hopkins Hospital
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Massachusetts
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Boston, Massachusetts, Estados Unidos, 02114
- Massachusetts General Hospital
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Missouri
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Saint Louis, Missouri, Estados Unidos, 63110
- Washington University
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New York
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Syracuse, New York, Estados Unidos, 13210
- SUNY Upstate Medical Center
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North Carolina
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Durham, North Carolina, Estados Unidos, 27705
- Duke University
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Oregon
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Portland, Oregon, Estados Unidos, 97213
- Providence ALS Center
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Pennsylvania
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Philadelphia, Pennsylvania, Estados Unidos, 19102
- Drexel University College of Medicine, Dept of Neurology
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University Park, Pennsylvania, Estados Unidos, 17033
- Penn State
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Texas
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San Antonio, Texas, Estados Unidos, 78229
- The University of Texas Health Science Center at San Antonio
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Vermont
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Burlington, Vermont, Estados Unidos, 05401
- University of Vermont
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Critérios de participação
Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.
Critérios de elegibilidade
Idades elegíveis para estudo
18 anos e mais velhos (Adulto, Adulto mais velho)
Aceita Voluntários Saudáveis
Não
Gêneros Elegíveis para o Estudo
Tudo
Descrição
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
Plano de estudo
Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Randomizado
- Modelo Intervencional: Atribuição cruzada
- Mascaramento: Quadruplicar
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
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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.
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Placebo correspondente em cápsulas administradas em dose oral única.
250 mg de CK-2017357 em cápsulas administradas em dose oral única.
Outros nomes:
500 mg de CK-2017357 em cápsulas administradas em dose oral única.
Outros nomes:
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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.
|
Placebo correspondente em cápsulas administradas em dose oral única.
250 mg de CK-2017357 em cápsulas administradas em dose oral única.
Outros nomes:
500 mg de CK-2017357 em cápsulas administradas em dose oral única.
Outros nomes:
|
|
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.
|
Placebo correspondente em cápsulas administradas em dose oral única.
250 mg de CK-2017357 em cápsulas administradas em dose oral única.
Outros nomes:
500 mg de CK-2017357 em cápsulas administradas em dose oral única.
Outros nomes:
|
|
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.
|
Placebo correspondente em cápsulas administradas em dose oral única.
250 mg de CK-2017357 em cápsulas administradas em dose oral única.
Outros nomes:
500 mg de CK-2017357 em cápsulas administradas em dose oral única.
Outros nomes:
|
|
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.
|
Placebo correspondente em cápsulas administradas em dose oral única.
250 mg de CK-2017357 em cápsulas administradas em dose oral única.
Outros nomes:
500 mg de CK-2017357 em cápsulas administradas em dose oral única.
Outros nomes:
|
|
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.
|
Placebo correspondente em cápsulas administradas em dose oral única.
250 mg de CK-2017357 em cápsulas administradas em dose oral única.
Outros nomes:
500 mg de CK-2017357 em cápsulas administradas em dose oral única.
Outros nomes:
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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ALSFRS-R
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 2 days
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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)
Prazo: 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)
Prazo: 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)
Prazo: 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)
Prazo: 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
Prazo: 2 days
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Sub-Maximum Grip Strength Fatigability is measured using the DynEx Electronic Hand.
Dynamometer
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2 days
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Número de pacientes com eventos adversos
Prazo: 4 semanas
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4 semanas
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Characterize the relationship, if any, between the plasma concentration of CK-2017357 and ALSFRS-R.
Prazo: 2 days
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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
Prazo: 2 days
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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.
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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 fatigability
Prazo: 2 days
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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.
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2 days
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Characterize the relationship, if any, between the plasma concentration of CK-2017357 and shoulder extension fatigue
Prazo: 2 days
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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
Prazo: 2 days
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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
Prazo: 2 days
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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.
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2 days
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Characterize the relationship, if any, between the plasma concentration of CK-2017357 and sniff inspiratory pressure
Prazo: 2 days
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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.
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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 muscle contraction
Prazo: 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.
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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
Prazo: 2 days
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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.
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2 days
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Effect of CK-2017357 on patient determined global functional assessment
Prazo: 2 days
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Patients will be asked to assess whether they feel the same, better or worse as compared to how they felt pre-dose
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2 days
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Effect of CK-2017357 on investigator determined global functional assessment
Prazo: 2 days
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Investigator will assess whether they the patient appears the same, better or worse as compared to the patient's status at pre-dose
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2 days
|
Colaboradores e Investigadores
É aqui que você encontrará pessoas e organizações envolvidas com este estudo.
Patrocinador
Investigadores
- Cadeira de estudo: Jeremy M Shefner, MD, PhD, State University of New York - Upstate Medical University
Publicações e links úteis
A pessoa responsável por inserir informações sobre o estudo fornece voluntariamente essas publicações. Estes podem ser sobre qualquer coisa relacionada ao estudo.
Datas de registro do estudo
Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.
Datas Principais do Estudo
Início do estudo
1 de março de 2010
Conclusão Primária (Real)
1 de novembro de 2010
Conclusão do estudo (Real)
1 de novembro de 2010
Datas de inscrição no estudo
Enviado pela primeira vez
16 de março de 2010
Enviado pela primeira vez que atendeu aos critérios de CQ
17 de março de 2010
Primeira postagem (Estimativa)
18 de março de 2010
Atualizações de registro de estudo
Última Atualização Postada (Real)
10 de maio de 2019
Última atualização enviada que atendeu aos critérios de controle de qualidade
7 de maio de 2019
Última verificação
1 de maio de 2019
Mais Informações
Termos relacionados a este estudo
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- CY 4021
Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .