An Open-label, Randomized, Crossover, Single Ascending Dose Pharmacokinetic Study of Continuous Subcutaneous Infusion of Lenalidomide Compared with Revlimid® Oral Capsules in Healthy Adult Male Subjects

Lenalidomide is a compound that is used for the treatment of multiple myeloma,
a type of blood cancer. The exact mechanism of action of lenalidomide is still
being studied. Researchers know that lenalidomide targets myeloma cells by
binding to a specific protein called cereblon. This protein is involved in
regulating the activity of proteins related to cell adhesion, metabolism, and
cell division. The binding of lenalidomide to cereblon triggers the death of
cancer cells as it affects the above processes. Lenalidomide also activates a
type of immune cell called a T cell. In addition, lenalidomide also inhibits
the formation of blood vessels in the vicinity of a tumor, affecting the blood
supply needed to fuel the tumor*s growth.

The purpose of this study is to investigate how quickly and to what extend
lenalidomide is absorbed and eliminated from the body (this is called
pharmacokinetics). In this study the pharmacokinetics will be compared when
lenalidomide is administered subcutaneous (under the skin) for a period of
24-hours continuously versus an oral dose with capsules.

We also investigate how safe the compound lenalidomide is and how well it is
tolerated when it is used by healthy participants.

Lenalidomide is not a new compound; it is already being used by patients.
Lenalidomide is already available on the market as an oral capsule under the
name Revlimid.

For the study it is necessary that subjects stay in the research center for 1
period of 6 days (5 nights). This will be followed by 1 short visit to the
research center. This short visit will take place between 3 and 7 days after
they leave the research center. In addition, we will call 1 time approximately
28 days after they leave the research center. They will then be asked about
your health.

Day 1 is the first day when they receive the study compound. They will leave
the research center on Day 5 of the study.

Below is an overview of the days you stay at the research center, or when they
visit the research center.

Screening -> Day -21 up to Day -1

Treatment Period - Arrival -> Day -1
Treatment Period - In-house stay -> Day -1 up to Day 5
Treatment Period - Departure -> Day 5

Follow-up - Visit -> 3 to 7 days after departure
Follow-up - Phone call -> Day 33 or Day 34


How will the study compound be administered?
Subjects will be given lenalidomide as an infusion (subcutaneous) under the
skin for 24 hours and as oral capsule(s) with 240 milliliters (mL) of water.
For the subcutaneous administration, you will have a cannula inserted under the
skin on your abdomen with a pump.

They will receive each administration once, so 2 administrations in total. The
order in which these administrations are given are shown in the table below.
They will be randomly assigned to Administration Sequence TR or RT.

Sequence | First administration (Day 1) | Second administration (Day 3)
Sequence TR | A 24-hour subcutaneous infusion, Administration T (Test
Administration) | Oral capsule(s), Administration R (Reference Administration)
Sequence RT | Oral capsule(s), Administration R | A 24-hour subcutaneous
infusion, Administration T

During the first 4 hours after administration of the oral capsule(s) they will
not be allowed to lie down (except when instructed to do so by one of the
investigators), as this may influence the uptake of the study compound.

One of the investigators will inspect hands and mouth after the intake of the
oral capsule(s). This it to check if they have taken the study compound.

The dose for the next group will only be increased if the lower dose of the
previous group was found to be well tolerated and in case of no objection by
the Medical Research Ethics Committee. The study will be discontinued if, in
the opinion of the investigators, unacceptable side effects appear.

The planned dose levels for the study are as follows:

Group 1 Day 1: once Lenalidomide 2.4 mg/day (100 µg/hour) subcutaneous infusion
or lenalidomide 5 mg oral capsule (1x5 mg)
Group 1 Day 3: once Lenalidomide 2.4 mg/day (100 µg/hour) subcutaneous infusion
or lenalidomide 5 mg oral capsule (1x5 mg)

Group 2 Day 1: once Lenalidomide 4.8 mg/day (200 µg/hour) subcutaneous infusion
or lenalidomide 10 mg oral capsules (2x5 mg)
Group 2 Day 3: once Lenalidomide 4.8 mg/day (200 µg/hour) subcutaneous infusion
or lenalidomide 10 mg oral capsules (2x5 mg)

Group 3 Day 1: once Lenalidomide 9.6 mg/day (400 µg/hour) subcutaneous infusion
or lenalidomide 20 mg oral capsules (4x5 mg)
Group 3 Day 3: once Lenalidomide 9.6 mg/day (400 µg/hour) subcutaneous infusion
or lenalidomide 20 mg oral capsules (4x5 mg)

Blood draw
Drawing blood may be painful or cause some bruising. The use of the indwelling
cannula (a tube in a vein in the arm) can sometimes lead to inflammation,
swelling, hardening of the vein, blood clotting, and bleeding in the
environment (bruising) 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 290 mL of blood. This amount does not cause any
problems in adults. To compare: a blood donation involves 500 mL of blood being
taken 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).

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 them to gag. When the sample is taken from the back of the
nose, they may experience a stinging sensation and the eyes may become watery.