Nuovo studio clinico di fase II
di CK-2017357
nei pazienti con SLA.
"Siamo lieti di annunciare questa prova successiva -
"dopo i risultati incoraggianti ottenuti nel 2010" -
nel nostro programma indirizzato alla valutazione del CK-2017357 nei pazienti con SLA",
ha dichiarato Jesse M. Cedarbaum, MD, vice presidente Cytokinetics 'di Ricerca
Clinica e Operazioni, Neuroscienze e malattie neuromuscolari. "
3 commenti:
Phase II Clinical Trial of CK-2017357 Opens for People with ALS
June 22, 2011
Click here for more information on enrollment
Cytokinetics, Incorporated announced on June 21, 2011, that the company has opened enrollment in a second Phase II clinical trial of CK-2017357 in patients with amyotrophic lateral sclerosis (ALS). CK-2017357, a fast skeletal muscle troponin activator, selectively activates the fast skeletal muscle troponin complex by increasing its sensitivity to calcium, which increases skeletal muscle force in response to neuronal input and delays the onset and reduces the degree of muscle fatigue. CK-2017357 is the lead drug candidate that has emerged from the company’s skeletal muscle contractility program.
This clinical trial is a double-blind, randomized, placebo-controlled trial designed to evaluate the safety and tolerability of multiple doses of CK-2017357 in patients with ALS. An estimated 24 patients are planned to be enrolled at eight to ten study centers in the United States. Patients in the trial will be randomized to one of four different treatment groups, to receive daily oral doses of placebo, 125 mg, 250 mg, or 375 mg of CK-2017357, respectively, for two weeks; clinical assessments will take place at pre-determined times during the course of treatment. Patients will also participate in follow-up evaluations one week after their final dose.
The primary objective of this clinical trial is to assess the safety and tolerability of CK-2017357, after multiple oral doses to steady state plasma concentrations, in patients with ALS. A secondary objective of this clinical trial is to evaluate the ALS Functional Rating Scale-revised (ALSFRS-R), other measures of pulmonary function, muscle strength and fatigue, and physician and patient global assessments in these patients while receiving two weeks of treatment with CK-2017357 at the indicated doses or placebo.
“We are pleased to announce this next trial in our program directed to the evaluation of CK-2017357 in patients with ALS,” stated Jesse M. Cedarbaum, M.D., Cytokinetics’ vice president of Clinical Research and Operations, Neuroscience and Neuromuscular Disorders. “This clinical trial is designed to complement our prior single-dose Phase IIa Evidence of Effect trial, which we successfully concluded in 2010, and now evaluate the safety and tolerability of CK-2017357 when administered daily to achieve steady state plasma concentrations.”
“This clinical trial is the seventh in a series of trials designed to evaluate CK-2017357 for the potential treatment of patients with muscle dysfunction or impairment. Progressing CK-2017357 into a Phase IIb clinical trial in 2012 in patients with ALS remains a priority for our company,” stated Robert I. Blum, Cytokinetics’ president and CEO. “We hope data from this clinical trial can inform a potential registration path for our novel mechanism drug candidate directed to the potential treatment of ALS patients.”
Update on Cytokinetics’ Skeletal Muscle Contractility Program
In addition to CK-2017357, Cytokinetics is also advancing back-up and follow-on skeletal muscle activators, each with different physiochemical properties, and intended to supplement Cytokinetics’ ongoing development activities. In addition to CK-2066260, the company has identified another potential drug candidate from its research directed to fasttwitch skeletal muscle activation. Cytokinetics is progressing both compounds in non-clinical research and development activities. The company does not have current plans to file an investigational new drug application (IND) for either of these compounds in 2011.
Development Status of CK-2017357
CK-2017357 is currently the subject of a clinical trials program that includes two completed Phase I studies in healthy volunteers and two completed Phase IIa Evidence of Effect clinical trials: one in patients with ALS and the other in patients with claudication associated with peripheral artery disease, all of which have been previously reported. In addition, a Phase IIa Evidence of Effect clinical trial in patients with myasthenia gravis is ongoing. CK-2017357 has been granted orphan-drug status by the United States Food and Drug Administration for the potential treatment of ALS.
In the Phase IIa Evidence of Effect clinical trial in patients with ALS, the single doses of CK-2017357 evaluated appeared safe and generally well-tolerated. In addition, both patients and investigators perceived a positive change in the patients’ overall status, in a dose-dependent fashion, at 6 hours after dosing with CK-2017357, based on a Global Assessment in which the patient and the investigator each independently assessed patients’ status compared to prior to dosing. Furthermore, there was a clear relationship between improvements in Global Assessments and the CK-2017357 plasma concentration. Improvements in the patients’ and investigators’ Global Assessments were associated with a trend towards decreased muscle fatigability, as evidenced by data from a test of sub-maximal hand-grip endurance. Data from this clinical trial also demonstrated a statistically significant, dose-related increase the maximum volume of air patients could inhale and exhale in ten seconds (Maximum Voluntary Ventilation) at both 6 and 24 hours after 500 mg of CK-2017357, as well as small but statistically significant increases in strength of certain muscle groups tested.
Una presentazione orale dal titolo "L'attivazione diretta del sarcomero scheletrico dal Activator Troponina, CK-2017357, un nuovo approccio per migliorare la funzionalità del muscolo scheletrico" è stato presentato da Malik Fady, MD, PhD, FACC, Vice Presidente, Biologia e Therapeutics, Cytokinetics, Inc., South San Francisco, in California, il 7 dicembre 2009. La presentazione ha evidenziato l'ipotesi terapeutiche sottostante scheletrico contrattilità Cytokinetics 'scoperta dei muscoli della droga e sviluppo. A seguito di una descrizione del meccanismo d'azione di CK-2017357, e cioè l'attivazione del complesso troponina veloce scheletrico muscolare con conseguente sensibilizzazione del sarcomero al calcio, la presentazione descritti tre conseguenze fondamentali farmacologica di questo meccanismo d'azione. La presentazione ha sottolineato che in studi non clinici, CK-2017357 e relativi attivatori troponina scheletrico amplificato la risposta all'ingresso del motoneurone, una maggiore potenza muscolare e rallentato lo sviluppo di affaticamento muscolare. Inoltre, la presentazione riassunti i dati non clinici indicano che CK-2071357 ritardato l'insorgenza della fatica muscolare in un modello di insufficienza vascolare e aumentare le prestazioni muscolari in un modello di resistenza muscolare. Infine, la presentazione recensione l'attuale piano di sviluppo per CK-2017357 compresa una discussione sulla fase due sono in corso studi clinici di CK-2017357 in volontari sani progettato per valutare la sicurezza, la tollerabilità e la farmacocinetica di dosi singole e multiple dosi, rispettivamente, come così come previsto prove di fase II di sperimentazione clinica effetto nei pazienti con malattie neuromuscolari o condizioni mediche associate con atrofia muscolare o fatica,
Posta un commento