A DOUBLE-BLIND RANDOMISED 2-ARM, 2-PERIOD CROSSOVER STUDY TO ASSESS THE SIMILARITY OF SAFETY AND PHARMACOKINETICS OF JHL1922 AND PULMOZYME® AFTER SINGLE AND REPEATED ADMINISTRATION IN HEALTHY SUBJECTS

JHL1922 is a new compound that may eventually be used to improve pulmonary
function in patients with cystic fibrosis (CF). Cystic fibrosis is a genetic
disorder in which mucus that is secreted by various body parts is unusually
thick. In the lung, this abnormally sticky mucus causes persistent lung
infections and limits the ability of CF patients to breathe over time.
Treatment consists of drugs that are inhaled to help clear this thick mucus
from the lung, including Pulmozyme®.

The active substance of JHL1922 (and Pulmozyme®) is called *dornase alpha*.
Dornase alpha is called *a biological* drug, because it is a large particle
made by living cells. Since the active substance of JHL1922 is similar to that
of Pulmozyme®, it is expected that the treatment effect of JHL1922 will be very
similar to Pulmozyme®, as intended.

The purpose of this study is to investigate how safe the new compound JHL1922
is when it is administered to healthy subjects. JHL1922 has not been
administered to humans before, but it has been previously tested in the
laboratory.

In this study, the safety of JHL1922 will be compared to the safety of
Pulmozyme®. Pulmozyme® is already approved and has been marketed to improve
pulmonary function in patients with cystic fibrosis since 1993. JHL1922 and
Pulmozyme® will first be administered as single dose of 2.5 mg, then after a
7-day gap as a single dose of 10 mg, and then, after a 7 day gap, as once daily
doses of 10 mg for 5 days.

This study will also investigate if and how JHL1922 is absorbed and eliminated
from the body (this is called pharmacokinetics) in comparison to Pulmozyme®.

The volunteers will receive JHL1922 and Pulmozyme® in 2 treatment periods
(Periods 1 and 2) as a liquid that is vaporized using a nebulizer and inhaled
into the lung. One dose consists of 2.5 mg. When taking 10 mg, they will take 4
consecutive doses of 2.5 mg. During administration of the study compound they
will sit down in an upright position.

The order in which they receive JHL1922 and Pulmozyme® in Periods 1 and 2 will
be determined by chance. Twelve volunteers will receive JHL1922 first followed
by Pulmozyme® and the other 12 volunteers will receive Pulmozyme® first
followed by JHL1922. Neither the volunteer, nor the responsible doctor knows
which order they will get; we call this *the study is blinded*. However, if it
is important for the health, for example in case of a serious adverse event,
this information can be looked up during the study.

The actual study will consist of 2 periods and during each period the
volunteers will have 3 long stays in the research center in Groningen at
location Martini Hospital. In each period they will stay in the research center
first for 4 days (3 nights), followed by 3 telephone calls, then again a stay
for 4 days (3 nights), followed by 3 telephone calls, and then a stay for 8
days (7 nights), followed by 3 telephone calls. There will be a final follow up
visit after Period 2.

Day 1 is the day of first administration (2.5 mg) of the study compound in each
period. They are expected at the research center at 11:00 h in the morning (Day
-1) prior to the day of first administration of the study compound. They will
be dosed on Day 1 and leave the research center on Day 3. They will be
contacted by phone in each period on Days 4, 5 and 6.

On Day 7, the volunteers are expected at the research center at 11:00 h in the
morning prior to the next administration (10 mg) of the study compound in each
period. The study compound will be administered on Day 8. They will then leave
the research center on Day 10. They will be contacted by phone in each period
on Days 11, 12 and 13.

On Day 14, they are expected at the research center at 11:00 h in the morning
prior to the next administration (10 mg) of the study compound in each period.
The study compound will be administered once daily on Days 15, 16, 17, 18, and
19. They will then leave the research center on Day 21. They will be contacted
by phone on Days 22, 23 and 24.

There are at least 7 days between the last dosing in Period 1 and the first
dosing in Period 2.

Not applicable.

Pain, minor bleedings, bruises, possibly an infection.