Randomized, Double-Blind, Controlled Trial Evaluating Cholecalciferol vs. Calcifediol for Severe Vitamin D Deficiency Correction

The primary objective of this clinical trial is to assess the **efficacy** of cholecalciferol in correcting 25-hydroxyvitamin D (25(OH)D) deficiency after 6 weeks of treatment in patients with severe vitamin D deficiency, compared to calcifediol. This is clinically relevant as severe vitamin D deficiency can lead to significant health issues, including bone disorders and impaired immune function, and effective correction is crucial for patient health.

Secondary objectives include:

• Assessing the efficacy in correcting 25(OH)D deficiency after 12 weeks of treatment.
• Evaluating the efficacy in correcting 25(OH)D deficiency after 6 and 12 weeks of treatment, according to classifications of post-treatment 25(OH)D values (insufficiency, sufficiency, optimal levels, and maximum levels).
• Evaluating the efficacy in maintenance of 25(OH)D correction after 12 weeks of treatment.
• Assessing the change in 25(OH)D levels after 6 and 12 weeks of treatment from baseline and after 12 weeks of treatment from 6 weeks of treatment.
• Assessing the difference in plasma profile of 25(OH)D throughout the study.
• Assessing the difference in vitamin D metabolism after 6 and 12 weeks of treatment from baseline and after 12 weeks of treatment from the values after 6 weeks of treatment.
• Evaluating the difference in other parameters of bone metabolism after 6 and 12 weeks of treatment compared to baseline values and after 12 weeks of treatment compared to values after 6 weeks of treatment.
• Assessing treatment compliance after 6 and 12 weeks of treatment.
• Assessing the degree of satisfaction perceived by the patient and investigator with the treatment after 6 and 12 weeks.
• Assessing the degree of treatment recommendation after 12 weeks as perceived by the investigator depending on the treatment group.
• Describing basal calcium intake.
• Assessing the safety of treatment during the study.

The clinical trial focuses on patients with **severe vitamin D deficiency**, specifically targeting adults of both sexes aged 18 years and older. The study population includes individuals with a body mass index ranging from 18.5 to 34.9 kg/m². Participants were required to have a 25(OH)D level of 12 ng/ml or lower to qualify for the study. The trial does not involve a vulnerable population, and both male and female subjects are included. The sponsor has not provided information regarding the total number of participants or specific lifestyle considerations such as diet or physical activity. Participants were selected based on their consent to participate and their compliance with the inclusion criteria. The trial aims to evaluate the efficacy of cholecalciferol in correcting vitamin D deficiency over a six-week period, compared to calcifediol.

The clinical trial is designed as a **randomized**, **blind**, and **controlled** study to evaluate the efficacy and safety of **cholecalciferol** in correcting 25(OH)D deficiency in subjects with severe **vitamin D deficiency**, compared to **calcifediol**. The trial will involve adult participants aged 18 years and older, with a body mass index between 18.5-34.9 kg/m², and a 25(OH)D level of ≤ 12 ng/ml. The study will span a total duration of 12 weeks, with the primary endpoint being the percentage of patients achieving 25(OH)D levels ≥ 20 ng/ml after 6 weeks of treatment.

Participants will be involved in the study for a maximum of 12 weeks, with the possibility of early termination if they do not adhere to the study protocol or if they experience adverse events that compromise their safety. The trial will commence with a screening visit to confirm eligibility based on the inclusion criteria. Following randomization, participants will undergo a baseline visit where initial measurements and assessments will be conducted. Subsequent study visits will occur at 6 weeks (Visit 2) and 12 weeks (Visit 3), where efficacy and safety parameters will be evaluated. The end-of-study visit will coincide with the 12-week mark, concluding the participant's involvement in the trial.

Throughout the study, participants will receive either cholecalciferol or calcifediol, administered orally in capsule form. The trial will assess both primary and secondary endpoints, including the percentage of patients achieving various 25(OH)D levels, changes in 25(OH)D concentrations, and differences in vitamin D and bone metabolism parameters. Safety will be monitored by recording the incidence of adverse events. The trial is categorized as a low-intervention study, aligning with Phase IV research objectives. The estimated recruitment start date is October 1, 2024, with an anticipated end date of July 31, 2025.

The clinical trial involves the administration of **colecalciferol**, marketed under the name Deltius 50,000 UI, in the form of hard capsules. Each capsule contains **colecalciferol** as the active ingredient, which is a chemical substance. The pharmaceutical form is a hard capsule, and the route of administration is oral. The maximum daily dose is 7,143 IU, with a total maximum dose of 350,000 IU over a treatment period of 12 weeks. The product is manufactured by ITALFARMACO S.A. and is authorized for use in Spain under the marketing authorization number 84413. The trial aims to evaluate the efficacy of **colecalciferol** in correcting severe vitamin D deficiency by assessing the increase in 25(OH)D levels after 6 weeks of treatment.

The comparator treatment in the study is **calcifediol**, which is also administered orally. The pharmaceutical form is denoted as PHF00160MIG, and the active substance is **calcifediol**, a chemical compound. The maximum daily dose for **calcifediol** is 38 µg, with a total maximum dose of 1,862 µg over the same 12-week treatment period. The trial is designed to compare the efficacy of **calcifediol** with **colecalciferol** in correcting 25(OH)D deficiency in subjects with severe vitamin D deficiency. Both treatments are administered under controlled conditions to ensure participant compliance and accurate assessment of outcomes.

The efficacy of the clinical trial will be assessed by evaluating the correction of **25(OH)D** deficiency in patients with severe vitamin D deficiency. The primary endpoint is the percentage of patients achieving **25(OH)D** levels ≥ 20 ng/ml after 6 weeks of treatment. Secondary endpoints include the percentage of patients achieving **25(OH)D** levels ≥ 20 ng/ml after 12 weeks, as well as various levels of **25(OH)D** after 6 and 12 weeks of treatment. Additionally, absolute and relative differences in **25(OH)D** concentrations will be measured at baseline, after 6 weeks, and after 12 weeks of treatment.

Plasma **25(OH)D** curves will be represented at three time points: baseline, after 6 weeks, and after 12 weeks of treatment. The study will also assess absolute and relative differences in vitamin D metabolism parameters and bone metabolism parameters at these time points. The degree of adherence to the treatment will be calculated after 6 and 12 weeks, and patient satisfaction with the treatment will be assessed using a Likert-type question. The investigator's degree of treatment recommendation will be evaluated after 12 weeks. Calcium intake will be assessed at baseline using the SEIOMM daily calcium intake calculator. The safety of the treatment will be monitored by recording the incidence of adverse events throughout the study period.