An Open-Label, Multi-Centre, Uncontrolled, Trial Investigating Degarelix One-Month Dosing Regimen Administered as Intermittent Androgen Deprivation (IAD) for One or More Cycles in Patients with Prostate Cancer Requiring Androgen Deprivation Therapy

Degarelix is a gonadotrophin releasing hormone (GnRH) receptor blocker
(antagonist). Degarelix is highly selective in binding to the GnRH receptor
resulting in the suppression of pituitary gonadotrophins, leading to
testosterone suppression.
Prostate cancer tissue contains clonal populations of testosterone dependent
and independent cells. In the androgen dependent cells, testosterone and its
metabolite dihydrotestosterone (DHT) stimulate cell proliferation via the
androgen receptors. In the absence of hormones, the growth of these
testosterone dependent cell populations will cease and result in a reduction of
tumor mass.
The main focus of the efficacy evaluation in the clinical development program
of degarelix is the ability to attain and sustain serum testosterone at or
below castrate levels (serum testosterone level <=0.5 ng/mL). Based on previous
clinical trials, a marketing authorisation application for degarelix 240/80 mg
one-month dose regimen has been submitted to EMEA and FDA on February 27th
2008.

Primary Objective - To evaluate the time to PSA >4 ng/mL during the first cycle
of IAD after the end of an induction period with degarelix (7 monthly
treatments) in prostate cancer patients
Secondary Objectives - To evaluate the time to PSA .4 ng/mL during the second
and subsequent cycles of IAD after the end of an induction period with
degarelix (7 monthly treatments).
To evaluate the time to PSA >4 ng/mL during the first cycle of IAD in patient
sub-groups and to determine the time to return to age-adjusted lower limit of
normal range or baseline level of testosterone during the first and subsequent
cycles of IAD after the end of an induction period with degarelix (7 monthly
treatments).
To evaluate disease specific Quality of Life during the induction degarelix
treatment and off-treatment periods during the first and subsequent cycles of
IAD.
To evaluate sexual function during the induction degarelix treatment and
off-treatment periods during the first and subsequent cycles of IAD.
To evaluate safety and tolerability during the induction degarelix treatment
and off-treatment periods during the first and subsequent cycles of IAD.

An open label design without control group using degarelix as IAD for one or
more cycles (7 monthly doses followed by a variable off-treatment period for
each patient). A visit is scheduled on a monthly basis during the induction
treatment period and every two months during the off-treatment period.

Degarelix will be administered as deep s.c. injections in the abdominal region.
A starting dose of 240 mg of degarelix (40 mg/mL) will be given on Day 0 as two
120 mg s.c. injections. Thereafter, 6 doses of 80 mg degarelix (20 mg/mL) will
be given 28 days apart via single s.c. injections.

Each patient is expected to have 10-20 visits for a total duration of up to 31
months. Patients will have physical examination, urinalysis and ECG at first
and last visit of the treatment period, and blood samples at each visit. The
amount of blood taken per visit will be between 10 and 30 mL. Quality of Life
questionnaire will be completed first and last visit of the treatment period
and every 6 months during off-treatment period.
Treatment with degarelix is likely to be associated with side effects similar
to those found with other treatments that reduce testosterone levels such as
hot flushes, increased sweating, loss of sex drive, impotence, and infertility.
Other side effects seen in the development phase of the trial drug include
fatigue, urinary tract infection, dizziness, constipation, anaemia, and
inflammation of the nasal part of the pharynx. Degarelix is well-tolerated at
the injection sites, the most reported reactions are injection site pain and
redness associated with the starting dose. Overall, the risks involved are
primarily anticipated to be mild to moderate.