The investigators are intending to perform a clinical study in healthy subjects on the pharmacokinetics of different doses of Hy.D Calcifediol compared to vitamin D3 (cholecalciferol) in order to gain insight into the dose response relationship and to assess kinetic differences including the steady state. The metabolites 1,25(OH)2D, 24,25(OH)2D will be assessed throughout the study to assess the metabolism of vitamin D vs. 25(OH)D. Vitamin D3 will be measured throughout the study to assess compliance with the restriction of exogenous vitamin D supplementation.
Reaching consistent levels of 25(OH)D has been shown to be crucial in decreasing falls, fractures and increasing calcium absorption. One way to circumvent the variability of 25(OH)D response to vitamin D might be to use calcifediol supplementation and bypass the 25-hydroxylase enzyme entirely. This approach also permits the physician to achieve desired serum levels in a matter of just a few days, rather than the several weeks required when using native vitamin D. Compared to native vitamin D, calcifediol is more water soluble, has a shorter half-life and increases 25(OH)D levels more quickly. Calcifediol is also more potent, about 3.5 times more potent in raising 25(OH)D levels than vitamin D. Its water solubility may also confer an advantage in patients who have difficulty absorbing fat soluble vitamins. This form of vitamin D metabolite has been used historically to increase calcium absorption, treat osteomalacia, and increase Bone Mineral Density (BMD). Using calcifediol seems to be a practical solution, but little is known about the dose response variability in humans and how it compares to that of native vitamin D. The investigators are intending to perform a clinical study in healthy subjects on the pharmacokinetics of different doses of Hy.D Calcifediol compared to vitamin D3 (cholecalciferol) in order to gain insight into the dose response relationship and to assess kinetic differences including the steady state. The metabolites 1,25(OH)2D, 24,25(OH)2D will be assessed throughout the study to assess the metabolism of vitamin D vs. 25(OH)D. Vitamin D3 will be measured throughout the study to assess compliance with the restriction of exogenous vitamin D supplementation.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
93
25(OH)D3 (Calcifediol Hy.D)
25(OH)D3 (Calcifediol Hy.D)
25(OH)D3 (Calcifediol Hy.D)
Plasma 25(OH)D concentration at several visits
Time frame: 6 months
AUC(day1-day183) of 25(OH)D, 1,25(OH)2D, 24,25(OH)2D and vitamin D
Time frame: 6 months
AUC(day1), Cmax(day1), Tmax(day1) and AUC(day182), Cmax(day182), Tmax(day182) of 25(OH)D, 1,25(OH)2D, 24,25(OH)2D and vitamin D
Time frame: 6 months
Time point at which the plasma level of ≥75 nmol/L 25(OH)D is reached (t)
Time frame: 6 months
Elimination rate and half-life of of 25(OH)D, 1,25(OH)2D, 24,25(OH)2D and vitamin D after cessation of supplementation
Time frame: 6 months
Serum calcium and creatinine, albumin, PTH, urine calcium and creatinine and vital signs throughout the study, (Serious) Adverse event assessment and reporting
Time frame: 6 months
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Vitamin D3 (Cholecalciferol)