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: Ulcerative colitis (UC), a chronic inflammatory bowel disease, affects approximately 5 million individuals worldwide, exerting a considerable influence on global health and economic systems. Among the challenges in UC management, treatment non-adherence stands out as a critical issue, often compromising therapeutic efficacy. One strategy to address this challenge is by reducing pill burden, which may improve patient compliance and optimize treatment outcomes. Methods: This randomized, two-sequence, four-period, crossover replicate study evaluated the pharmacokinetic profiles, bioequivalence, and safety of a newly developed 1500 mg mesalazine gastro-resistant tablet compared to three of the reference 500 mg Claversal^® gastro-resistant tablets (total dose 1500 mg) in 80 healthy participants under fasted conditions. Results: Bioequivalence between mesalazine formulations was observed in both the rate and extent of systemic bioavailability. The geometric mean ratios and their 90% CI were 102.51% (95.85–109.63) for AUC_0–∞, 103.36% (96.40–110.83) for AUC_0–t, 84.49% (78.24–91.24) for AUC_8–48h, and 114.24% (100.15–130.32) for C_max. All within the accepted bioequivalence ranges, confirming comparable pharmacokinetic performance. Secondary pharmacokinetic parameters such as t_max, t_1/2, K_e, Cl, and MRT were also consistent across both formulations. The incidence of adverse events was comparable between the two mesalazine formulations, with only flatulence and mild self-limited rash considered possibly related to test treatment. Conclusions: Overall, the 1500 mg formulation demonstrated a pharmacokinetic profile and tolerability comparable to the reference formulation, offering a higher-strength option to reduce daily pill burden. This strategy is of clinical relevance, particularly for improving treatment adherence among UC patients who need to take multiple pills daily to achieve their required dosage. While adherence is influenced by various factors, reducing pill burden may facilitate compliance and optimize therapeutic efficacy.

Objective: This study aimed to assess the bioequivalence of two oral methocarbamol formulations, as follows: the test (T) methocarbamol 1500 mg tablets and the reference (R) Robaxin® 500 mg tablets (3 tablets, total dose: 1500 mg) under fasting conditions, and compare their pharmacokinetic performance. Methods: This was a single-center, phase I, randomized, open-label (blinded for analytical determination), two-sequence, two-period, crossover, bioequivalence study. A total of 32 healthy volunteers were randomly assigned to receive the T-R or R-T administration sequence. Each volunteer received a single dose of each methocarbamol formulation (T or R) separated by a washout period of 7 days. To evaluate the pharmacokinetic profile, blood samples were collected at nineteen time points after dosing. Results: The arithmetic mean Cmax was 31.72 µg/mL for R and 32.39 µg/mL for T, and the arithmetic mean AUC0−t was 90.25 h × µg/mL and 89.72 h × µg/mL, respectively. All adverse events reported were mild for both formulations. The 90% confidence intervals for the corresponding logarithmically transformed geometric mean ratios of Cmax and AUC0−t fell within the acceptance interval of 80.00–125.00%, as their values were 91.67–112.47% for ln(Cmax) and 92.34–103.47% for ln(AUC0−t). Conclusion: Therefore, one tablet of methocarbamol 1500 mg was found to be bioequivalent to the Robaxin® 500 mg tablets (3 tablets), with comparable tolerability and safety profiles.

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.