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An orally administered, fixed-dose coformulation of sodium phenylbutyrate-taurursodiol (PB-TURSO) significantly slowed functional decline in a randomized, placebo-controlled, phase 2 trial in ALS (CENTAUR). Herein we report results of a long-term survival analysis of participants in CENTAUR. In CENTAUR, adults with ALS were randomized 2:1 to PB-TURSO or placebo. Participants completing the 6-month (24-week) randomized phase were eligible to receive PB-TURSO in the open-label extension. An all-cause mortality analysis (35-month maximum follow-up post-randomization) incorporated all randomized participants. Participants and site investigators were blinded to treatment assignments through the duration of follow-up of this analysis. Vital status was obtained for 135 of 137 participants originally randomized in CENTAUR. Median overall survival was 25.0 months among participants originally randomized to PB-TURSO and 18.5 months among those originally randomized to placebo (hazard ratio, 0.56; 95% confidence interval, 0.34-0.92; P = .023). Initiation of PB-TURSO treatment at baseline resulted in a 6.5-month longer median survival as compared with placebo. Combined with results from CENTAUR, these results suggest that PB-TURSO has both functional and survival benefits in ALS.

Introduction: Passive data from smartphone sensors may be useful for health‐care research. Our aim was to use the coronavirus disease‐2019 (COVID‐19) pandemic as a positive control to assess the ability to quantify behavioral changes in people with amyotrophic lateral sclerosis (ALS) from smartphone data. Methods: Eight participants used the Beiwe smartphone application, which passively measured their location during the COVID‐19 outbreak. We used an interrupted time series to quantify the effect of the US state of emergency declaration on daily home time and daily distance traveled. Results: After the state of emergency declaration, median daily home time increased from 19.4 (interquartile range [IQR], 15.4‐22.0) hours to 23.7 (IQR, 22.2‐24.0) hours and median distance traveled decreased from 42 (IQR, 13‐83) km to 3.7 (IQR, 1.5‐10.3) km. The participant with the lowest functional ability changed behavior earlier. This participant stayed at home more and traveled less than the participant with highest functional ability, both before and after the state of emergency. Discussion: We provide evidence that smartphone‐based digital phenotyping can quantify the behavior of people with ALS. Although participants spent large amounts of time at home at baseline, the COVID‐19 state of emergency declaration reduced their mobility further. Given participants' high level of daily home time, it is possible that their exposure to COVID‐19 could be less than that of the general population. [ABSTRACT FROM AUTHOR]

Introduction: Three studies evaluated safety, tolerability, pharmacokinetics, and pharmacodynamics of CK-2127107 (CK-107), a next-generation fast skeletal muscle troponin activator (FSTA), in healthy participants. We tested the hypothesis that CK-107 would amplify the force-frequency response of muscle in humans.Methods: To assess the force-frequency response, participants received single doses of CK-107 and placebo in a randomized, double-blind, 4-period, crossover study. The force-frequency response of foot dorsiflexion following stimulation of the deep fibular nerve to activate the tibialis anterior muscle was assessed.Results: CK-107 significantly increased tibialis anterior muscle response with increasing dose and plasma concentration in a frequency-dependent manner; the largest increase in peak force was ∼60% at 10 Hz.Discussion: CK-107 appears more potent and produced larger increases in force than tirasemtiv-a first-generation FSTA-in a similar pharmacodynamic study, thereby supporting its development for improvement of muscle function of patients. Muscle Nerve 57: 729-734, 2018. [ABSTRACT FROM AUTHOR]