Safety and immunogenicity of 15-valent pneumococcal conjugate vaccine in pneumococcal vaccine-naïve adults ≥50 years of age.

BACKGROUND: Pneumococcal disease remains a public health priority in adults. Safety and immunogenicity of 15-valent pneumococcal conjugate vaccine (PCV15) containing 13 serotypes included in 13-valent pneumococcal conjugate vaccine (PCV13) plus 2 additional serotypes (22F and 33F) was evaluated in adults ≥50 years old (NCT01513551). METHODS: 691 adults received one dose of PCV15, PCV13, or 23-valent pneumococcal polysaccharide vaccine (PPV23) and were followed 14 days for safety. Serotype-specific IgG geometric mean concentrations (GMCs) and opsonophagocytic activity (OPA) geometric mean titers (GMTs) were measured immediately prior and 1-month postvaccination. RESULTS: Safety profiles were comparable across vaccination groups. PCV15 induced comparable levels of IgG GMCs and OPA GMTs to PCV13 and PPV23 for shared serotypes. Serotype-specific antibodies were numerically higher among recipients of PCV15 than PCV13 and PPV23 for 7 and 12 shared serotypes, respectively; and lower for 4 and 1 serotype(s), respectively. PCV15 induced higher IgG and OPA antibodies than PCV13 or PPV23 for serotypes unique to PCV15 (22F and 33F not in PCV13; 6A not in PPV23). CONCLUSIONS: PCV15 displayed an acceptable safety profile and induced IgG and OPA to all 15 serotypes included in the vaccine, at levels comparable to PCV13 and PPV23 for shared serotypes with these vaccines. Study identification: V114-002. CLINICALTRIALS.GOV identifier: NCT01513551. © 2018 Merck & Co., Inc.

Effects of suvorexant, an orexin receptor antagonist, on sleep parameters as measured by polysomnography in healthy men.

STUDY OBJECTIVES: Suvorexant (MK-4305) is an orexin receptor antagonist being developed for the treatment of insomnia. This report describes the effects of nighttime administration of suvorexant on polysomnography (PSG) sleep parameters in healthy young men. DESIGN: Randomized, double-blind, placebo-controlled, 4-period crossover PSG study, followed by an additional 5(th) period to assess pharmacokinetics. SETTING: Sleep laboratory. PARTICIPANTS: Healthy young men between 18 and 45 years of age (22 enrolled, 19 completed). INTERVENTIONS: Periods 1-4: suvorexant (10 mg, 50 mg, or 100 mg) or placebo 1 h before nighttime PSG recording. Period 5: suvorexant 10 mg, 50 mg, or 100 mg. MEASUREMENTS AND RESULTS: In Periods 1-4, overnight sleep parameters were recorded by PSG and next-morning residual effects were assessed by psychomotor performance tests and subjective assessments. Statistically significant sleep-promoting effects were observed with all doses of suvorexant compared to placebo. Suvorexant 50 mg and 100 mg significantly decreased latency to persistent sleep and wake after sleep onset time, and increased sleep efficiency. Suvorexant 10 mg significantly decreased wake after sleep onset time. There were no statistically significant effects of suvorexant on EEG frequency bands including delta (slow wave) activity based on power spectral analysis. Suvorexant was well tolerated. There was no evidence of next-day residual effects for suvorexant 10 mg. Suvorexant 50 mg statistically significantly reduced subjective alertness, and suvorexant 100 mg significantly increased reaction time and reduced subjective alertness. There were no statistically significant effects of any suvorexant dose on digit symbol substitution test performance. In Period 5, plasma samples of suvorexant were collected for pharmacokinetic evaluation. The median T(max) was 3 hours and apparent terminal t(½) was 9-13 hours. CONCLUSIONS: In healthy young men without sleep disorders, suvorexant promoted sleep with some evidence of residual effects at the highest doses.

Single- and multiple-dose pharmacokinetics and tolerability of telcagepant, an oral calcitonin gene-related peptide receptor antagonist, in adults.

Telcagepant is a novel, orally active, and selective calcitonin gene-related peptide receptor antagonist being developed for acute treatment of migraine with and without aura. Three separate clinical studies were conducted to evaluate the pharmacokinetics and tolerability of telcagepant following single oral doses in healthy young and elderly men and women and multiple oral doses in men. Telcagepant was rapidly absorbed with a time to maximum concentration of approximately 1.5 hours. The terminal half-life was approximately 6 hours. A greater than dose-proportional increase was observed in the area under the plasma concentration versus time curve from zero to infinity. Following twice-daily dosing, with each dose separated by 2 hours, steady state was achieved in approximately 3 to 4 days with an accumulation ratio of approximately 2. There were no clinically meaningful pharmacokinetic differences when compared across age and gender. Telcagepant was generally well tolerated up to single doses of 1200 mg and multiple doses of 400 mg twice daily.