A single centre, open label trial investigating the absorption, metabolism and excretion of somapacitan after single subcutaneous dosing in healthy male subjects

Somapacitan is a new investigational compound that may eventually be used for
the treatment of growth hormone deficiency in children (GHD) and in adults
(AGHD). Growth hormone deficiency slows the growth and physical and mental
development in children. In adults, growth hormone (GH) deficiency leads to
increased body fat, decreased bone density and muscle mass, and increased risk
for cardiac and arterial diseases. The study compound is a modified human GH,
which has been modified to prolong its efficacy with the aim of reducing the
frequency of injections. Normal GH has to be administered once daily as a
subcutaneous (sc) injection (an injection under the skin) whereas somapacitan
is expected to be effective when administered as a sc injection once weekly.
Somapacitan is in development and is not registered as a drug but has been
given to humans before.

The purpose of the study is to investigate how quickly and to what extent
somapacitan is absorbed, metabolized (broken down) and eliminated from the body
(this is called pharmacokinetics). Somapacitan will be labeled with tritium
(3H, a radioactive hydrogen isotope) and is thus radioactive (also called
radiolabeled). In this way somapacitan can be traced in blood, urine, feces and
expired air. It will also be investigated to what extent somapacitan is
tolerated.

At the first visit the volunteer will have to stay in the clinical research
center in Groningen, location Martini hospital, for 16 days (15 nights).

The further participation to the study will depend on the amount of
radioactivity left in urine and feces on Day 15. The amount of radioactivity in
urine and feces will be measured from Day 13 onwards. The volunteer should be
aware that when the radioactivity levels are still above the pre-defined levels
on Day 15, additional 24-hour periods (maximum 3 periods) will be scheduled for
the collection of urine and feces until the radioactivity levels are below the
pre-defined levels.

The 24-hour periods will take place on Day(s) 21-22, 28-29 and 35-36 and the
volunteer is expected in the clinical research center at 11:00 h in the morning
on Day(s) 21, 28 and 35; the volunteer can leave after the 24-hour collection
interval. The volunteer will be informed whether he is expected for an
additional 24-hour collection interval as soon as the data are available.

During the study the volunteer will receive radiolabeled somapacitan as a sc
injection.

The volunteer will receive a single dose of 6 mg radiolabeled somapacitan as a
sc injection.

The safety profile of somapacitan has been evaluated in four completed clinical
studies in healthy subjects, and in adults and children with growth hormone
deficiency. The subjects received single or multiple doses of the study
compound. Overall, the study compound was well tolerated and most adverse
events were mild.

The expected adverse events were weight increased, fatigue, blood glucose
increased, edema, asthenia, headache, paresthesia, but some patients did not
experience adverse events at all. Subcutaneous administration of somapacitan
can, like any other drugs for injection, occasionally lead to undesired local
side effects, such as redness, swelling, itching, and tenderness of the skin at
the point of injection. In the four completed studies, the local injections
site reactions were overall mild and transient.

Overall, the safety profile of somapacitan observed so far is similar to the
existing growth hormone products for daily administration e.g. Norditropin®.
The safety profile of Norditropin® has been firmly established by the results
of clinical trials and the wide post-authorization use globally as described in
Norditropin®FlexPro® package leaflet. Most frequent adverse events are
peripheral edema, headache, paresthesia, arthralgia, joint stiffness, and
myalgia.

This study compound might trigger the formation of antibodies to growth hormone
which has been observed previously with other protein hormones including human
growth hormone. Antibody formation may hinder the efficacy of the treatment.
However, in healthy subjects and in adults and children with growth hormone
deficiency treated with the study compound, antibody development was not
observed.

In rare cases, the injection of protein drugs including somapacitan and
ingredients can cause local or systemic allergic reactions. Systemic reactions
can cause e.g. sudden breathing problems, nausea and vomiting, fast heart beat
or dizziness. If these reactions are observed, you should contact a doctor
immediately. In healthy subjects and in adults and children with growth hormone
deficiency, allergic reactions related to the study compound were not observed.

In order to take blood samples, your doctor will need to draw blood from your
veins. Occasionally, you may feel a little discomfort, bruising, bleeding or
swelling at the site of needle insertion for withdrawal of the blood samples.
There is also a very small risk of infection at the place where the needle goes
into your vein.

In this study radiolabeled somapacitan will be used. The amount of
radioactivity in this dose will be approximately 20 MBq (MBq = megaBecquerel,
this is a unit to express the amount of radioactivity in the study compound).
The average environmental background radiation burden in The Netherlands is
approximately 2 mSv per year (mSv = milliSievert, this unit indicates the
burden on the human body; thus the effect on the human body of the amount of
radioactivity administered). The additional radiation burden in this study due
to the administration of approximately 20 MBq radiolabeled somapacitan is
calculated to be less than 0.5 mSv. This is approximately 25% of the average
annual radiation burden.