Bilastine, a second-generation antihistamine, is approved in Europe for the treatment of allergic rhinoconjunctivitis and urticaria in adults and children aged ≥ 6 years. Pharmacokinetic data for children aged 6–11 years were extracted post hoc from a study in which children (2–11 years) with allergic rhinoconjunctivitis or urticaria received oral bilastine (10 mg/day). Maximum plasma concentration (C_max) and area under the plasma concentration curve (AUC) data were compared with adult pharmacokinetic data from seven clinical studies (bilastine 20 mg/day). Safety data for children aged 6–11 years were extracted post hoc from a phase III randomized controlled trial of children (2–11 years) with allergic rhinoconjunctivitis or chronic urticaria receiving once-daily bilastine 10 mg or placebo for 12 weeks. Exposure and C_max values were similar for children (6–11 years) and adults: median pediatric/adult ratios for AUC_0–24 and C_max were 0.93 and 0.91, respectively. There was no significant difference in the incidence of treatment-emergent adverse in children (6–11 years) receiving bilastine 10 mg or placebo. Conclusion: Pharmacokinetic and safety analyses in children aged 6–11 years support the suitability of the pediatric dose of bilastine 10 mg and confirm that the safety profiles of bilastine and placebo are similar. What is Known: • Bilastine, a second-generation antihistamine, is approved in Europe for the treatment of allergic rhinoconjunctivitis and urticaria in adults (20 mg/day) and children aged ≥ 6 years (10 mg/day). • An ontogenic model based on adult data and pharmacokinetic/pharmacodynamic simulations supported the selection of a bilastine dose of 10 mg/day in children aged 2–11 years. Bilastine 10 mg/day was shown to have a safety profile similar to that of placebo in a large phase III randomized clinical trial in children aged 2–11 years. What is New: • As bilastine is approved in Europe for children aged ≥6 years, the current study reports the results of two post hoc analyses of pharmacokinetic and safety data in children aged 6–11 years. • Analysis of pharmacokinetic and safety data in children aged 6–11 years supports the suitability of the pediatric dose of bilastine 10 mg and confirms that its safety profile is similar to that of placebo.

Background/Objective: Optimal vitamin D levels are required for bone health and proper functionality of the nervous, musculoskeletal and immune systems. The objective of this study was to assess the efficacy and safety profiles of new weekly calcifediol formulations with the potential to improve adherence and outcome. Methods: A Phase II-III, double-blind, randomized, multicentre trial (EudraCT 2020-001099-14 and NCT04735926). Subjects were randomized 2:2:1 to calcifediol 75 µg, 100 µg and placebo. 25(OH)D levels were measured at 4, 16, 24, 32 and 52 weeks. The main outcome was the percentage of subjects who achieved a response defined as 25(OH)D levels ≥20 ng/mL and/or ≥30 ng/mL at week 16. Results: 398 subjects (51.1 ± 15.96 years, 74.2% females, 98.7% Caucasian) with plasma 25(OH)D levels between 10 and 20 ng/mL were randomized. A total of 376 subjects completed 16 weeks of treatment, and 355 subjects completed the study. Six patients withdrew due to an adverse event, all unrelated to treatment. At week 16, 93.6% and 74.4% of subjects receiving calcifediol 75 µg achieved response levels of ≥20 ng/mL and ≥30 ng/mL, respectively. The calcifediol 100 µg group showed 98.7% and 89.9% of responders for ≥20 ng/mL and ≥30 ng/mL, respectively. Both calcifediol groups showed superiority over placebo at each response level at all time points analyzed (p < 0.0001). Calcifediol treatments increased 25(OH)D levels from baseline to week 24 and remained stable thereafter. The frequency of treatment-emergent adverse events was balanced between groups. Conclusions: New weekly calcifediol 75 and 100 µg formulations showed an effective and sustained response with a good long-term safety profile.

Background/Objectives: Given the crucial health benefits of vitamin D, addressing severe deficiencies is a pressing medical concern. This study aimed to evaluate the effectiveness and safety of two new weekly doses of calcifediol (100 µg and 125 µg) for long-term management in patients with severe vitamin D deficiency, defined as plasma 25(OH)D levels ≤10 ng/mL. Methods: This study was a randomized, two-cohort, controlled, double-blind, multicentre phase II–III trial. Subjects were randomized 2:2:1 to weekly calcifediol 100 µg, 125 µg or a placebo. The primary endpoint was the proportion of patients achieving plasma 25(OH)D levels of ≥20 ng/mL and/or ≥30 ng/mL by week 16. Results: A total of 276 patients (mean age: 55.2 years, SD 15.42) were randomized. By week 16, 92.3% and 91.8% of patients in the calcifediol 100 µg and 125 µg groups, respectively, reached ≥20 ng/mL, compared to 7.3% in the placebo group. Levels of ≥30 ng/mL were achieved by 49% (100 µg) and 76.4% (125 µg) of participants, with none in the placebo group. Calcifediol demonstrated superior efficacy at all response levels and time points (p < 0.0001). Plasma 25(OH)D concentrations increased by week 24 and remained stable. The incidence of adverse events was comparable across groups. Conclusions: A weekly calcifediol dose of 100 µg demonstrates the best profile of efficacy and tolerability, providing a reliable solution for achieving and maintaining adequate vitamin D levels in patients with severe deficiency.

Background/Objectives: Adequate vitamin D levels are critical for overall health, yet vitamin D deficiency remains prevalent. This study aims to evaluate the efficacy and safety of a standardized weekly supplementation regimen of 100 μg calcifediol for patients with varying degrees of vitamin D deficiency. Methods: A post hoc pool analysis was conducted from a randomized, double-blind, placebo-controlled, multicenter, two-cohort trial. Cohort 1 included vitamin D mild deficiency patients (25(OH)D levels > 10 < 20 ng/mL) and Cohort 2 severe deficiency patients (25(OH)D levels ≤ 10 ng/mL). As both had placebo and weekly calcifediol 100 μg arms (ratio 1:2), a pooled analysis of safety and efficacy was conducted. The primary outcome was the percentage of subjects achieving 25(OH)D levels ≥ 20 ng/mL and/or ≥30 ng/mL at various time points. Results: A total of 401 participants across both cohorts were included in the analysis, 130 who received a placebo and 271 calcifediol 100 µg weekly. By week 52, 94.5% of individuals in the calcifediol group achieved 25(OH)D levels ≥ 20 ng/mL, compared to 25.3% in the placebo group (p < 0.0001). At this same week, 80.5% of subjects in the calcifediol group, but none in the placebo group (p < 0.0001), had 25(OH)D levels ≥ 30 ng/mL. The mean 25(OH)D level plateaued around 40.7 ng/mL from weeks 16 to 52. The frequency of treatment-emergent adverse events was similar in both groups, placebo and calcifediol. Conclusions: Weekly supplementation of 100 μg calcifediol effectively restores vitamin D levels in individuals with both mild and severe deficiencies, demonstrating a favourable safety profile.

Background/Objective: Given the high prevalence of vitamin D deficiency, particularly among older women, this post hoc analysis was conducted to evaluate the long-term efficacy and safety of weekly calcifediol 100 µg in women with vitamin D deficiency participating in a randomised, double-blind, phase II/III trial. Methods: A total of 261 women were included (calcifediol, n = 192; placebo, n = 69). The primary objective was to compare the proportions of women achieving serum 25(OH)D concentrations ≥20 ng/mL or ≥30 ng/mL over the 12-month treatment period. Exploratory analyses of body mass index (BMI) and menopausal status were performed. Results: Weekly calcifediol 100 µg demonstrated superior efficacy versus placebo from week 4 in women achieving ≥20 ng/mL (68.2% vs. 5.8%; p < 0.001) or ≥30 ng/mL (21.4% vs. 0%; p < 0.001), and consistently higher proportions were maintained through week 52. Mean 25(OH)D concentrations increased from 12.21 ng/mL at baseline to 39.47 ng/mL at week 16, and remained stable (41–43 ng/mL) thereafter. No significant differences were observed across BMI or menopausal status subgroups. The safety profile of weekly calcifediol 100 µg was similar to placebo, with no evidence of toxicity. Conclusions: Weekly calcifediol 100 µg is a safe and effective option for achieving and maintaining adequate vitamin D levels in vitamin D-deficient women over a period of 12 months, and is associated with consistent effects across BMI and menopausal status.