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The objective of this phase 1 study was to evaluate the pharmacokinetics (PK), pharmacodynamics, and cardiac effect following administration of ponesimod (a selective sphingosine‐1‐phosphate receptor modulator) and propranolol in healthy adults. In treatment period (TP) 1, participants received ponesimod (2 mg). In TP2, if resting heart rate (HR) was ≥ 55 bpm, the ponesimod up‐titration regimen was initiated. Participants were randomized to TP2A (placebo plus ponesimod up‐titration) or TP2B (80 mg propranolol plus ponesimod up‐titration). Concomitant administration resulted in an increased bradyarrhythmic effect on HR versus ponesimod alone. The mean maximum difference in mean hourly HR from time‐matched baseline for TP2B compared with TP2A during the first 12 h post‐dose was −12.4 bpm. This was observed after the first dose of ponesimod, persisted for the first 4 doses, then decreased to −7.4 bpm post‐up‐titration. The lowest mean of the HRnadir in TP2B was 48.9 bpm (95% CI: 46.4–51.3). There was no significant difference in the occurrence of 1st degree AV block between groups and no occurrences of 2nd or higher degree AV block. No clinically relevant changes were observed in the PK of ponesimod or propranolol. Overall, 88.5% of participants experienced ≥ 1 AE during the study. In TP2, the most reported TEAEs (≥ 5%) considered related to ponesimod were fatigue (12 [25.5%]) and dizziness (10 [21.3%]). No deaths were reported. Co‐administration of ponesimod with propranolol resulted in a greater HR‐lowering effect compared to ponesimod alone, without significant changes in PK parameters or serious cardiac adverse events in healthy adults.

Rationale Suvorexant is a first-in-class orexin receptor antagonist for treating insomnia. There is a general concern that hypnotics may impair next-morning driving ability. Objective The objective of this study was to evaluate next-morning driving performance in older adults after single and repeated doses of suvorexant. Methods Double-blind, randomized, placebo-controlled, 4-period crossover study in 24 healthy volunteers (10 females), aged 65–80 years. Subjects were treated with suvorexant (15 and 30 mg) for eight consecutive nights, zopiclone 7.5 mg nightly on days 1 and 8, and placebo. Driving performance was assessed on days 2 and 9 (9 h after dosing) using a 1-h standardized highway driving test in normal traffic, measuring standard deviation of lateral position (SDLP). Drug-placebo differences in SDLP >2.4 cm were considered to reflect clinically meaningful driving impairment. Results Driving performance as measured by SDLP was not impaired following suvorexant. Mean drug–placebo differences in SDLP following suvorexant 15 and 30 mg on day 2 and 9 were 0.6 cm or less. Their 90 % CIs were all below the threshold of 2.4 cm for clinical relevance and included zero, indicating effects were not clinically meaningful or statistically significant. Symmetry analysis showed no significant differences between the number of participants who had SDLP differences >2.4 cm and those who had SDLP differences <−2.4 cm following suvorexant. Conclusions There was no clinically meaningful residual effect of suvorexant 15 and 30 mg on next-morning driving (9 h after bedtime dosing) in healthy older adults, as assessed by mean changes in SDLP and by the number of participants on drug versus placebo that exceeded a predetermined threshold for clinically meaningful impairment.

Influenza vaccines remain largely underused. A promising alternative to current intramuscular vaccines is a trivalent inactivated influenza vaccine (TIV) delivered using a microinjection system to offer a less invasive and possibly more acceptable vaccination. A phase II, multicentre, randomised open-label study in 978 healthy adults (18–57 years) evaluated the immunogenicity and safety of intradermal TIV. Subjects received a 0.1 ml injection of intradermal TIV, containing 9 μg of haemagglutinin (HA) per strain ( n = 588) or a conventional 0.5 ml intramuscular vaccine (15 μg of HA/strain; n = 390). Intradermal TIV induced non-inferior humoral immune responses against all three strains and superior responses against both A strains (H1N1, H3N2) compared with the control. Both vaccines were well tolerated.