Trial Information

A Phase 2, Multicenter, Open Label Study of the Safety and Efficacy of High-Dose Pulse Administration DN-101 (Calcitriol) in Patients With Myelodysplastic Syndrome

DN-101 is an experimental drug that has not been approved by the Food and Drug
Administration (FDA). It is a newly formulated pill that contains high amounts of
calcitriol, a naturally occurring hormone and the biologically active form of vitamin D.
The natural vitamin D found in dairy products or in typical vitamin pills, must be
chemically changed by the liver and kidney into calcitriol before it is biologically active.
The body normally uses small amounts of calcitriol to regulate its blood calcium levels.
However, for any possible therapeutic effect, MDS patients require much higher levels of
calcitriol than the body can produce from dietary vitamin D. DN-101 provides MDS patients
with high doses of calcitriol in a pill form.

Laboratory studies have demonstrated evidence supporting the use of calcitriol in MDS. High
dose calcitriol slows the growth of leukemic cells (cancerous cells) and increases the
growth of normal bone marrow cells. Some patients with MDS may have low levels of
calcitriol in their bone marrow.

Clinical study results in patients with MDS have been mixed– some positive and some negative
results. Elevated calcium in the blood occurred frequently and prevented the use of higher,
more potentially therapeutic doses.

Novacea tested a new formulation of calcitriol, DN-101, in a Phase 1 study. In that study
the maximum tolerated dose of DN-101 that did not cause high blood calcium levels when given
weekly for several months was determined. That dose is within the range that is potentially
therapeutic for MDS patients and will be used in this MDS study.

The purposes of this study are to determine if HDPA DN-101 treatment:

- increases the number of red blood cells, white blood cells, and platelets in the blood

- reduces the number of blood transfusions

- reduces the number of serious infections requiring antibiotics

- reduces the number of serious bleeding events

- improves fatigue