A MULTI-CENTER, RANDOMIZED, CROSS-OVER, DOUBLE-BLIND, THIRD PARTY OPEN, PLACEBO CONTROLLED, PILOT STUDY TO ASSESS THE URODYNAMIC EFFECTS OF MODIFIED RELEASE UK-369,003 IN MEN WITH LOWER URINARY TRACT SYMPTOMS (LUTS)

UK-369,003 is a highly selective and potent inhibitor of Phosphodiesterase
(PDE) 5.
UK-369,003 has negligible activity against PDEs 1-4 and 7-11 (IC50*s >2000 nM
cf.
IC50 of 1.4 nM against human corpus cavernosum derived PDE5). It has increased
selectivity for PDE5 over PDE6 (>80 fold) compared to sildenafil (~10 fold). Two
recently completed studies (A3711029 and A3711030) have demonstrated efficacy
in treating ED. UK-369,003 improves ED by reducing the catabolism of cGMP by
PDE5, enhancing smooth muscle relaxation of the corpus cavernosum. UK-369,003
was well tolerated in both studies.
(Further information is available in the UK-369,003 investigator*s brochure.)

A pilot study to:
1. assess the urodynamic changes induced by 100mg MR formulation
of UK-369,003 vs. placebo in men with LUTS;
2. Assess the safety and tolerability of UK-369,003 in men with LUTS

A multi-center double blind, randomized, placebo-controlled, third party open,
crossover phase II pilot study with two treatment arms. Following a washout
period of up to 4-weeks subjects will undergo a baseline assessment (BL) of
their bladder storage and voiding function. They will then be randomized (1:1
ratio) to either once daily 100mg MR UK-369,003 or placebo for a minimum of 2
weeks. The subjects will then have an end of first treatment period (EOT1)
pressure flow study assessment. This will be followed by a 2-4 week washout
period. The subjects will then attend for period 2. At the beginning of
treatment period (BOT2) subjects will attend the clinic to receive medication
and complete patient outcome measures but will not undergo any urodynamics.
After receiving study treatment for a minimum of 2 weeks an end of second
treatment period (EOT2) pressure flow study assessments will be conducted.
This will be followed by a follow-up visit 1 week after the EOT2 which in the
absence of adverse events, may be conducted by phone.
Interim analyses may be conducted as the study is ongoing. These will be
performed by a third party at Pfizer. The results of these analyses will not
enable individuals directly involved in the execution of the study (such as the
investigators, sponsor*s operational team and central urodynamics reader) to
identify treatment assignments for subjects until after the study is completed.

Formulation and Packaging
UK-369,003 will be supplied as 50mg Modified Release tablets presented as blue
and white, round bilayer tablets. Matching placebo will be provided.
Each dose will consist of 2 tablets of either 50mg Modified Release or placebo
to
match. Sufficient supplies for 2 weeks with up to 7 days overage will be
provided so that if it is necessary for subjects to re-arrange a planned clinic
visit they may do so and still continue receiving medication.

Administration
Subjects will take two tablets orally with a glass of water every morning.
These must be swallowed whole, one after the other, and without chewing.

UK-369,003 is similar to a drug known as sildenafil (Viagra®). These drugs work
by inhibiting an enzyme (a chemical substance found in the body) present in the
penis (known as PDE5). Results from tests, some of which used animals, show
that the same chemical pathway that the body uses for relaxing muscles around
the penis that enables an erection to take place may also affect tissues in the
body used to control urination. Therefore some of the side effects of
UK-369,003 may be similar to those seen with Viagra®.

SIDE EFFECTS
Thus far, UK-369,003 has been administered to over 1200 patients and healthy
volunteers at different dosages. Based on research studies and the experience
of other people who have received UK-369,003 some side effects may occur.
UK369,003 has been well tolerated with the most common side effects being
headache, vasodilatation (flushes), rhinitis (nasal congestion), dyspepsia,
erections, dizziness, muscular pain and back pain.
All these effects were generally short term and weak to moderate in intensity.
Additional side effects include: changes in colour vision, conjunctivitis and
diarrhea. Although these events were reported during treatment with UK369,003,
they were not necessarily caused by it.
As with all new drugs there may be unforeseen side effects but we do not expect
you to suffer any health problems by taking part in this study. If any
significant facts or side effects appear during this study, you will be
notified.
Some new problems or side effects could happen; if this should occur, you will
be told of any changes in the way the study is done. You will also be told of
any new risks or side effects. This information may affect your decision about
continuing in the study.
You will be informed as soon as possible of any new findings relevant to this
study.

DISCOMFORTS
Some men may find bladder filling and catheterization uncomfortable although
they should not be painful. You may have some discomfort passing urine for 1 or
2 days after the procedure and may also notice some blood in your urine; this
is normal. If the discomfort is considerable or lasts longer than 2 days, then
please speak with the study doctor. There is small risk of urinary tract
infection after bladder filling which can be treated with antibiotics.

POSSIBLE BENEFITS OF THE STUDY
You will get study drug and all medical treatment in this study at no cost to
you. You may have a good response to the treatment. Others may benefit from the
information learned from the study. It is also possible that you will receive
no direct health benefit from being in this study.