Bioequivalence study for vitamin D3 pharmacokinetic parameters following single oral administrations of vitamin D3 1000 IU with cyclodextrin and vitamin D3 1000 IU without cyclodextrin in Caucasian healthy volunteers

Vitamin D3 is used to prevent or correct a lack of vitamin D in the human body.
In a normal situation, vitamin D can be synthesised by the human body by
exposure of the body to sunlight. Also, vitamin D is obtained from ingested
food. A lack of vitamin D may be caused by insufficient intake together with
inadequate exposure of the body to sunlight or conditions that inhibit the
uptake of vitamin D and is frequent in Europe. A lack of vitamin D may lead to
a decreased bone mineralisation and finally to conditions that soften the bone.
In addition, vitamin D has other functions in the body and a lack of vitamin D
may play a role in cardiovascular diseases and cancer.

The purpose of the study is to investigate whether the cyclodextrin added to
the cholecalciferol formulation has an effect on the vitamin D3 availability in
the body. Thus, it will be investigated if concentrations of vitamin D3 that
are found in the blood following administration of a known formulation of
stabilized vitamin D3 (without cyclodextrin) differ from those found following
administration of vitamin D3 with cyclodextrin.

The actual investigation will consist of 2 treatments periods. There is a fixed
period of 7 days between the day of drug administration of the first period
(Period 1 Day 1) and the day of drug administration of the second period
(Period 2 Day 1, being Day 8 of the entire study). You will stay in the
clinical research centre in Zuidlaren from the morning 3 days before drug
administration in the first period (morning of Day -3) up to 3 days after drug
administration in the second period (Period 2 Day 4, being Day 11 of the entire
study). Thus, you will stay in the clinical research centre for 14 days (13
nights).

1 single dose of Vitamin D3 with cyclodextrine on Day 1 or 8 and 1 single dose
of Vitamin D3 without cyclodextrine on Day 1 or 8

Procedures: pain, light bleeding, heamatoma, possibly an infection.

There is no general consensus on the maximum safe daily dose of vitamin D3, but
generally in the Netherlands a dose of 50 micrograms per day is assumed to be
the safe maximum. This is twice the amount that will be given on each day of
study drug administration in this study.
The risk that these two administrations can cause signs of overdosing is very
small.

The side effects reported with the intake of Vitamin D3 include:
- Uncommon side effects (affecting less than 1 in 100 people): too much calcium
in your blood (hypercalcaemia), you may feel or be sick, lose your appetite,
have constipation, stomach ache, feel very thirsty, have muscle weakness,
drowsiness or confusion, too much calcium in your urine (hypercalciuria).
- Rare side effects (affecting less than 1 in 1000 people): skin rash, itching,
hives.

With the doses used in this study no serious adverse effects are expected. The
occurrence of known or other effects cannot be excluded. All drugs cause
adverse events to some extent.