PHASE I, DOUBLE BLIND, PLACEBO-CONTROLLED, DOSE-ESCALATION STUDY TO ASSESS THE SAFETY, TOLERABILITY, AND PHARMACOKINETICS OF FMX-8 IN HEALTHY MALE VOLUNTEERS

FMX-8 is a new investigational compound that may eventually be used for the
treatment of anemia due to chronic diseases (e.g. cancer and kidney disease).
FMX-8 is in the development stage and is not registered as a drug. This is the
first time that this compound is being given to humans.

Primary:
To determine the safety, tolerability, and pharmacokinetic (PK) profile of
single ascending intravenous (iv) doses and of multiple ascending iv doses of
FMX-8 in healthy subjects

Secondary:
To evaluate the pharmacodynamics (PD) of FMX-8 in iron parameters

Exploratory:
To evaluate the circulating hepcidin level upon FMX-8 treatment

A double-blind, placebo-controlled, dose-escalation Phase I study to assess
the safety, tolerability, and pharmacokinetics of FMX-8 in healthy male
subject.

The study will consist of 2 parts (SAD and MAD part):
In Part 1 (SAD), up to 40 subjects (5 dose groups of 8 subjects) will receive
escalating single iv doses (as a 30 minute infusion on Day 1) of FMX-8 or
placebo in a ratio of 3:1 (FMX-8:placebo. Dose levels for part 1 will be
escalated per group depending on the results of the preceding group. Dose level
will start at 0.3 mg/kg FMX-8 and not exceed 30 mg/kg) . Dose levels most
likely will be 0.3 mg/kg, 1 mg/kg, 3 mg/kg, 10 mg/kg, and 30 mg/kg.

In Part 2 (MAD), up to 30 subjects (3 dose groups of 10 subjects) will receive
a total of 4 iv doses of FMX-8 or placebo in 2 weeks (as 30 minutes infusions
on Days 1, 4, 7 and 10) in a ratio of 4:1 (FMX-8:placebo). The initial doses
for the MAD will be selected from within the range of doses already tested in
the single ascending dose (SAD) cohorts. Tentative dose levels are 0.3 mg/kg, 3
mg/kg and 30 mg/kg
In addition, subjects participating in Part 2 will receive two times (Day 1 and
Day 10) a standard iron tablet (a commercially available, over-the-counter
brand), containing 325 mg ferrous sulfate, equivalent to 65 mg iron).

Procedures and assessments during the study:
Screening , follow-up and during study: demographics, body weight and height
(including body mass index calculation), medical history, drug and alcohol
screen, cotinine test, blood sampling for serology (HBsAg, anti HCV and
anti-HIV 1/2), clinical chemistry, hematology, coagulation, pharmacokinetics,
pharmacodynamics and immunogenicity and Heart trace (ECG*s)

The study will consist of 2 parts (SAD and MAD part):

Part 1 (SAD) will consist of 5 dose groups (of 8 subjects), each group will
stay in the clinical research centre in Groningen for 5 days (4 nights)

Part 2 (MAD) will consist of 3 dose groups (of 10 subjects) each group will
stay in the clinical research centre in Groningen for 14 days (13 nights)

During the study subjects will receive FMX-8 or inactive formulation (placebo)
after a fasting period (no food or drinks, except water) of at least 10 hours
by an infusion directly into a vein. This infusion will take 30 minutes.
In Part 1 per group 6 participants will receive FMX-8 and 2 participants will
receive placebo; the participants will each receive one dose.
In Part 2, per group 8 participants will receive FMX-8 and 2 participants will
receive placebo; the participants will each receive four doses of either FMX-8
or placebo.

Whether you will receive the active drug or placebo will be determined by
chance. Neither the participant nor the investigator knows if FMX-8 will be
dosed

From 1.5 hour after end of the infusion subjects will receive a breakfast.
During fasting subjects are allowed to drink water.

During the study several assessments will be conducted differing in extent and
the nature of burden:

Blood draws will be taken via direct puncture or an indwelling canula: It is
anticipated that for part 1, 1 time(s) an indwelling canula will be used and 16
blood draws will be drawn by direct puncture of the vein and for part 2, 2
time(s) an indwelling canula will be used and 37 blood draws will be drawn by
direct puncture of the vein.
Studymedication will be administered by an infusion directly into a vein for
this purpose an indwelling canula will be inserted, this is in addition to the
indwelling canula used for blood sampling. Thus during some dosing occasions
subjects will have a canula inserted in both arms. The canula for the infusion
will be removed immediately after each dosing.
Possible side effects of an indwelling canula are pain, light bleeding,
heamatoma, possibly an infection.

Heart trace (ECG*s) will be made regularly.

See section E9 for a description of the risk related to participation in this
study