A trial to assess the injection site pain experience of excipient solutions relevant for subcutaneous injection

The aim of this study is to determine whether and how much the various study
products could cause (or relieve) pain/discomfort.

When a medicine is made for administration under the skin, the stability of the
product is important. Another important thing, but sometimes overlooked, is
that the medicine should not cause local discomfort around the injection site.
For this reason excipient solutions should be chosen to minimize discomfort
with the injection.

The primary objective is to assess, in healthy subjects with a body mass index
(BMI) greater than or equal to 25.0 kg/m2, the injection site pain experience
of 9 excipient solutions (Trial Products 4 to 12), intended to be used in
future subcutaneous medicinal products, normal saline (Trial Product 1) and a
positive control (Trial Product 3) relative to a negative control (Trial
Product 2).

The study will consist of 2 days during which the volunteer will stay in the
research center for about 7 hours per day. At the end of Day 1 volunteer will
be discharged and volunteer must return to the research center the following
day (Day 2).

Volunteer will be tested for the presence of coronavirus upon admission to the
research center on both days. Until the test results are available, volunteer
will be separated from other volunteers and only have very limited contact with
study staff. This is to avoid virus spread from potentially infected volunteers
to other volunteers or to the study staff. Until the results are available, it
is not certain whether volunteer is infected or not and can thus potentially
infect others. The test results will be available within 1 hour. If the
volunteer test positive for coronavirus, he/she cannot participate in the
study.

Before the first administration of a study product a grid will be drawn on
volunteers abdomen with a permanent marker. This grid must still be visible
until 7 days after the last injection to be able to assign any local reactions
to the appropriate study product.

Each study product will be given as an injection under the skin. On each of the
days (Day 1 and Day 2) the volunteer will receive 3 injections on the left side
and 3 injections on the right side of the abdomen, 12 injections over 2 days in
total. There will be a minimum of 30 minutes between 2 consecutive injections.
After each injection the volunteer is asked to fill in questionnaires about the
level and type of pain that he/she may experience around the injection site
during and after the injection.
During the 30 minutes after each injection the volunteer must stay in bed or be
seated in a chair, and not walk around.

In this study only excipient solutions or a saline solution will be injected,
solutions without active ingredients. These excipient solutions are being used
or may be used for Novo Nordisk pipeline drugs. The excipients are already
included in solutions for approved products within the EU and/or US. Some of
the 12 study products may cause mild to moderate injection site pain.

Drawing blood may be painful or cause some bruising. In addition the amount of
injections might cause some bruising on the abdomen.
In total about 20 mL of blood will be taken.

To make a heart tracing, electrodes will be pasted at specific locations on the
arms, chest and legs. Prolonged use of these electrodes can cause skin
irritation (rash and itching).

A sample for the coronavirus test will be taken from the back of the nose and
throat using a swab. Taking the sample 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 volunteer to gag. When the sample is taken from the back
of the nose, volunteer may experience a stinging sensation and the eyes may
become watery.