A randomized, 2 part, 4-treatment, 2-way cross-over study in healthy volunteers to compare the pharmacokinetic and pharmacodynamics profiles of 1 *g/kg of DA-3880 and EU sourced AND EU Aranesp® (AMGEN) after single intravenous or subcutaneous administration

Aranesp® is a drug registered for the treatment of symptomatic anemia in
patients with chronic renal failure, and patients receiving chemotherapy for
the treatment of cancer. Aranesp® is the brand name, the active ingredient is
called darbepoetin-*, which is a modified human erythropoietin (EPO). EPOs
regulate the growth and maturation of red blood cells.

DA-3880 is developed to be a copy of Aranesp®. DA-3880 consists of several
parts (building blocks) that are present in the human body by nature (like the
building blocks of Aranesp®). Therefore, the drug is called *a biological*.
This is the first time that the DA-3880 compound is being given to humans.

The purpose of the study is to investigate to what extent DA-3880 is absorbed
and eliminated from the body (this is called pharmacokinetics) as compared to
the above mentioned Aranesp® formulation. In addition, the effect DA-3880 on
the number of red blood cells will be investigated (this is called
pharmacodynamics), and it will be investigated to what extent DA-3880 is
tolerated. For the purpose of the study the concentration of darbepoetin-* and
the possible development of antibodies against darbepoetin-* in your blood will
be investigated.

This study will be performed in 60 healthy male/female volunteers, divided over
2 parts, each divided in 2 groups. The first group of each part will be divided
in 2 subgroups for the first administration. In each part 2 volunteers will be
dosed, one with DA-3880 and one with Aranesp®. After dosing, the safety and
tolerability of DA-3880 or Aranesp® will be closely monitored for at least 24
hours. Only if there are no concerns about the safety and tolerability the
remaining subjects of the first groups will be dosed.

The actual study will consist of 2 periods during which you will stay in the
clinical research center in Zuidlaren for 8 days (7 nights) followed by 2 days
(Day 10 and 13 [Day 1 is the day of administration of study medication]) during
which you will visit the clinical research center in Zuidlaren. The time
interval between the two administrations is 28 days.

During the study the volunteer will receive DA-3880 or Aranesp® after a
breakfast, starting 30 minutes before medication administration and which has
to be completed before administration of the study medication.

The overall risks of DA-3880 administration are considered to be minimal,
although some are unforeseeable as the testing of this drug is still at an
early stage. As DA-3880 will be administered to humans in this study for the
first time, adverse effects in humans have not been reported to date. With the
dose used in this study no serious adverse effects are expected, but as all
drugs may potentially cause adverse events to some extent, the occurrence of
known or other effects cannot be excluded. This means that there is a chance of
a minor side effect and a remote chance of something serious happening. It is
expected that DA-3880, which is being developed as a copy of Aranesp® and which
has an active ingredient similar to Aranesp®, will also likely have the same
adverse effects as Aranesp®.

The most common side effects for Aranesp® found in patients are:
hypersensitivity reactions, hypertension, rash, redness of the skin, injection
site pain, edema, convulsions and stroke. In some cases anti-bodies to Aranesp®
caused anemia.

Most of the side effects known for Aranesp® were reported by patients with
chronic renal failure or cancer patients receiving chemotherapy, who use the
drug for a long period of time. In this study only healthy volunteers will be
included, who will receive 2 doses. Therefore it is thought that the
probability of the events described below to happen in this study is very low.

The body may recognize DA-3880 and Aranesp® as foreign. As a result an immune
response can occur, for example by making antibodies against the study
medication. In case teh volunteer would develop in the future symptomatic
anemia as a result of chronic renal failure or cancer and that should be
treated with one of the medications used in this study, the medication may show
less or no effect. This may mean that in such a case, the volunteer may require
higher doses of DA-3880 or Aranesp® to overcome these antibodies if still
present, or the volunteer would require another medication for his/her
treatment.

Procedures: pain, minor bleeding, bruising, possible infection