A SINGLE ORAL ASCENDING DOSE STUDY TO INVESTIGATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS AND PHARMACODYNAMICS OF RO6836191 IN HEALTHY MALE VOLUNTEERS INCLUDING A SINGLE INTRAVENOUS DOSE OF RO6836191

RO6836191 is a new investigational compound that may eventually be used for the
treatment of cardiovascular diseases. RO6836191 inhibits the production of
aldosterone, a hormone which plays an important role determining cardiovascular
and renal damage during cardiovascular diseases, leading to a reduction in
blood pressure. This is the first time that this compound is being given to
humans.

The study will be performed in 2 parts, Parts 1 and Part 2.
The purpose of this study is to investigate to what extent RO6836191 is
tolerated. It will also be investigated how quickly and to what extent
RO6836191 is absorbed and eliminated from the body (this is called
pharmacokinetics). In addition the effect of RO6836191 on aldosterone levels
will be investigated (this is called pharmacodynamics).

In Part 2 the effect of a low salt diet on the pharmacodynamics of RO6836191
will also be investigated. In addition, the pharmacokinetics of intravenous
RO6836191 administration will be compared with oral (via the mouth) RO6836191
administration.

Part 1:
The study consists of 1 period, during which RO6836191 or placebo will be
given.

In Group 1 only, first 2 male volunteers will be dosed on the same day (1 will
receive RO6836191, and 1 will receive placebo) before the rest of the group
will be dosed. After dosing, the safety and tolerability of RO6836191 in these
volunteers will be closely monitored. If there are no concerns about the safety
and tolerability, then the remaining 6 volunteers (5 will receive RO6836191 and
1 will receive placebo) will be dosed at least 1 day after the first 2
volunteers have been dosed.

A Cortrosyn test will be performed in Group 3 to 7. During this test a hormone
is injected, which stimulates the production of aldosterone and cortisol. The
levels of aldosterone and cortisol in blood will be determined both before and
30 minutes after injection of the hormone, by taking a blood sample. This test
will be performed both before and after RO6836191 or placebo has been given.


Part 2:
The actual study will consist of 3 Periods. The time interval between the
different Periods is at least 7 days. In the first 2 Periods, the study
medication will be given once during a low salt and once during a normal diet.
During Period 3, a single dose of RO6836191 will be given intravenously

Part 1:
During the study the study medication will be given after a fasting period (no
food or drinks) of at least 8 hours as a drinking solution at a volume of 50 to
100 milliliters. The bottle containing the study medication will be rinsed at
least twice with 50 milliliters of tap water which needs to be drunk by the
volunteers. Per group 6 participants will receive RO6836191 and 2 participants
will receive placebo.

Part 2:
During Periods 1 and 2, the study the study medication will be given after a
fasting period (no food or drinks) of at least 8 hours as a drinking solution
at a volume of 50 to 100 milliliters. The bottle containing the study
medication will be rinsed at least twice with 50 milliliters of tap water which
needs to be drunk by the volunteers. Per group 6 participants will receive
RO6836191 and 2 participants will receive placebo.
During Period 3 a 30 minute during intravenous infusion of RO6836191 will be
given after a fasting period (no food or drinks) of at least 8 hours.

canula insertion in each period
single blood draws
IV dosing in Part 2, once
in Part 2, low salt diet during 1 period
2x ocular assessment with ophthalmologist in Part 1