An open-label, randomized, single center, crossover study in healthy participants to assess lipoprotein lipase activity and levels, and triglyceride levels after heparin exposure, in both fasted and postprandial state

Heparin is no new compound; it is a registered drug that is used to prevent the
formation of blood clots. It is used to treat and prevent blood clots caused by
certain medical conditions or medical procedures. It is also used before
surgeries to reduce the risk of blood clots.

In this study, heparin is used to release more lipoprotein lipase in the blood
stream.

In this study we will investigate biomarkers in blood after exposure to heparin
in the fasted state or after a high-fat meal. Biomarkers are proteins present
in the blood. The biomarkers investigated in this study are proteins that are
involved in the metabolism and transport of lipids in the blood. Disrupted
activity of these biomarkers affects energy balance in the body, insulin
action, body weight maintenance, and cardiovascular disease risk. The main
biomarkers that will be investigated in this study are lipoprotein lipase and
triglycerides. It is known that following heparin administration, an increased
amount of lipoprotein lipase is released in the blood stream which has effects
on other specific biomarkers. However, the difference in the effects on
lipoprotein lipase and other biomarkers between administration of heparin in
the fasted state or after a high-fat meal has not been well-studied up to date.
Therefore, the current study will be conducted.

Heparin will be administered as an intravenous injection in this study. In this
study, the effects of administration of heparin will be compared with the
effects of administration of normal saline which will also be administered as
an iv injection. Normal saline is a mixture of salt and water and is commonly
used in infusions in hospitals. Normal saline has no effect on the biomarkers
that will be investigated in this study. Please note that when the term *study
compound* is used in this document, we mean heparin, normal saline, or both.

For the study it is necessary that the volunteer stays in the research center
for 1 period of 7 days (6 nights). The volunteer is expected at the research
center at 14:00 h in the afternoon prior to Day 1, the day of first
administration of the study compound. The time of entry may be changed. If this
happens the volunteer will be informed about it in advance. The volunteer will
leave the research center in the afternoon of Day 6 of the study.

Below an overview of the days of visit and stay at the research center:

Screening:
On a day between Day -21 and Day -2

Arrival:
Day -1

In-house stay:
Day -1 up to Day 6

Departure:
Day 6

Telephonic follow-up:
On a day between Day 11 and Day 14

The volunteer will get heparin and normal saline administered as an iv
injection in the fasted state and after a high-fat meal.

There will be 2 groups and both groups will receive 6 treatments in a different
order. You will be assigned to 1 of these groups; this will be determined by
chance.

The treatments per group per day are as follows:

Group 1
Day
Treatment
When Nutritional state
1 25 international units per kilogram body weight (IU/kg) heparin
Morning After a high-fat meal
2 25 IU/kg
heparin
Morning Fasted
3 Normal
saline
Morning Fasted
4 50 IU/kg
heparin
Morning After a high-fat meal
5 50 IU/kg
heparin
Morning Fasted
6 Normal
saline
Morning After a high-fat meal

Group 2
Day
Treatment
When Nutritional state
1 50 IU/kg
heparin
Morning After a high-fat meal
2 50 IU/kg
heparin
Morning Fasted
3 Normal
saline
Morning Fasted
3 25 IU/kg
heparin
Morning After a high-fat meal
4 25 IU/kg
heparin
Morning Fasted
5 Normal
saline
Morning After a high-fat meal

When the study compound will be administered in the fasted state in the morning
(Days 2, 3, and 5), this will take place after you have fasted for at least 10
hours prior to administration of the study compound.

When the study compound will be administered after a high-fat meal in the
morning (Days 1, 4 and 6), this will take place after you have fasted for at
least 10 hours prior to the start of the high-fat meal. The study compound will
then be administered at 30 minutes after the start of the high-fat meal.

Drawing blood may be painful or cause some bruising. The use of the indwelling
cannula can sometimes lead to inflammation, swelling, hardening of the vein,
blood clotting, and bleeding in the environment of the puncture site. In some
individuals, a blood draw can sometimes cause pallor, nausea, seating, low
heart rate, or drop in blood pressure with dizziness or fainting.

In total, we will take about 492 mL of blood from the volunteer from screening
to discharge. This amount does not cause any problems in adults. To compare: a
blood donation involves 500 mL of blood being taken at once each time. If the
investigator thinks it is necessary for the safety of a participant, extra
samples might be taken for possible additional testing. If this happens, the
total amount of blood drawn may be more than the amount indicated above.

Heart tracing
To make a heart tracing, electrodes (small, plastic patches) will be placed on
arms, chest and legs. Prolonged use of these electrodes can cause skin
irritation (rash and itching).

High-fat meals/Fasting
The volunteer has to be able to consume a high-­fat meal completely in the
morning of 3 different days. The high-fat meal contains eg, 2 fried eggs, fried
potatoes, bacon, and 2 slices of (toasted) (wheat) bread with margarine. The
volunteer must consume the whole meal within 20 minutes. It can be difficult to
consume the entire meal, particularly for light eaters.

The fasting for a prolonged time during the study may lead to symptoms such as
dizziness, headache, stomach upset, or fainting.

Coronavirus test
Samples for the coronavirus test will be taken from the back of the nose and
throat using swabs. Taking the samples only takes a few seconds, but can cause
discomfort and can give an unpleasant feeling. Taking a sample from the back of
the throat may cause the volunteer to gag. When the sample is taken from the
back of the nose, the volunteer may experience a stinging sensation and the
eyes may become watery.