A Phase 1 Study to Evaluate the Safety and Pharmacokinetics following Administration of Single and Multiple Doses of the Anti-Staphylococcal Lysin, LSVT-1701, in Healthy Adult Subjects

Thirty-two healthy male subjects (8 per cohort) were randomized 6:2 to active:placebo. LSVT-1701, an anti-staphylococcal lysin, was administered intravenously as a 6 mg/kg single dose and as 1.5, 3, and 4.5 mg/kg twice daily for 4 days. LSVT-1701 exposure increased in a greater than dose proportional manner and did not accumulate. Treatment-emergent adverse events (TEAEs) were predominantly of mild intensity. The most common TEAEs were chills, pyrexia, headache, infusion site events, cough, rhinorrhea, and increases in C-reactive protein.

A phase 1 study to assess potential interaction between ASP8062 and alcohol in healthy adult subjects

Background: ASP8062 is a novel orally active GABAB receptor positive allosteric modulator in clinical development for the treatment of alcohol use disorder (AUD) and opioid use disorder (OUD). Aims: This study assessed the potential pharmacokinetic/pharmacodynamic interaction between ASP8062 and alcohol under single-dose conditions in healthy adults. Methods: A double-blind, placebo-controlled, crossover phase 1 study was conducted in which 20 subjects were randomly assigned to four treatment sequences (ASP8062 + alcohol; ASP8062 + placebo alcohol; placebo + alcohol; placebo + placebo alcohol) each consisting of four treatment periods, separated by washout periods of at least 14 days. An analysis of variance was used to assess pharmacokinetic interaction and a mixed-effects analysis of covariance was used to assess pharmacodynamic interaction. Results/outcomes: After administration of alcohol, a mild to minimal increase in plasma exposure (AUCinf and Cmax) of ASP8062 was observed, but tmax and t½ for ASP8062 remained unchanged after administration of alcohol. In contrast, ASP8062 did not affect the AUClast and Cmax of ethanol. No clinically relevant differences in cognition measurements were observed with ASP8062 compared with placebo, but there were expected impairments in psychomotor and executive function with alcohol alone. ASP8062 in combination with alcohol resulted in worse scores in cognition measurements than alcohol alone, but this potentiation was not consistent. ASP8062 administered alone was safe and well-tolerated and safety findings in subjects administered alcohol alone were not augmented when ASP8062 was administered in combination with alcohol. Conclusion/interpretation: The data support further clinical studies investigating ASP8062 in patients with AUD.

The Complicated Relationship between Dieting, Dietary Restraint, Caloric Restriction, and Eating Disorders: Is a Shift in Public Health Messaging Warranted?

The origins of theories specifying dietary restraint as a cause of eating disorders can be traced to the 1970s. This paper will present an overview of the origins of dietary restraint theories and a brief historical review of evidence will be summarized. Recent research will be presented, including the results from the CALERIE Phase 1 study, as well as CALERIE Phase 2, which were NIH-sponsored randomized controlled trials. CALERIE 2 provided a test of the effect of two years of caloric restriction (CR) on the development of eating disorder syndromes and symptoms in comparison to a control group that did not alter eating behavior or body weight. The intervention was effective for inducing a chronic (two-year) reduction in total energy expenditure and increased dietary restraint but did not increase symptoms of eating disorders. The results of this recent investigation and other studies have not provided experimental support for conventional dietary restraint theories of eating disorders. These findings are discussed in terms of potential revisions of dietary restraint theory, as well as the implications for a paradigm shift in public health messaging related to dieting.