A single-center, open-label, two sequence, crossover study to investigate the interaction between Colistin Methansulfonate Sodium (CMS) and RO7033877 in healthy subjects.

RO7033877 is an investigational compound that may eventually be used for the
treatment of serious infections, including pneumonia acquired while in the
hospital. *Investigational* means that RO7033877 is in the clinical trial phase
of development and it has not been approved by the regulatory authority for
general clinic use yet. RO7033877 has been given to humans before in clinical
studies. RO7033877 works through a new mechanism of action compared to other
antibiotics. It binds to a specific protein in the outer membrane of bacteria.
This protein is essential for the transport of the membrane building blocks to
the outer membrane of the bacteria. When RO7033877 binds to this protein, the
bacteria can no longer grow and multiply.

The other drug that will be given is colistin methanesulfonate (CMS), which is
an approved antibiotic for the treatment of specific serious infections.

The purpose of the study is to investigate how quickly and to what extent
RO7033877 and CMS are getting into your blood stream and how long your body
takes to get rid of it (this is called pharmacokinetics) when they are given
alone or given at the same time. The study will also look at how safe and well
tolerated the combined administration of CMS and RO7033877 is.

The study will consist of minimally 2 and maximally 3 periods during which you
will receive the following: in one period you will receive multiple doses of
CMS alone for 2.5 days, and in the other periods you will receive multiple
doses of RO7033877 alone (Period 1 or 2), multiple doses of CMS alone (Period 1
or 2), and for 2 days, followed by multiple doses of RO7033877 and CMS together
(Period 3) for 2.5 days. You will be randomly assigned (similarfor up to
flipping a coin) to receive either RO7033877 or CMS in the 2.5 days.

The study will consist of 3 periods during which the volunteer will receive
multiple doses of RO7033877 alone (Period 1 or 2), multiple doses of CMS alone
(Period 1 or 2), and multiple doses of RO7033877 and CMS together (Period 3)
for 2.5 days. The volunteers will be randomly assigned (similar to flipping a
coin) to receive either RO7033877 or CMS in the first period (7 volunteers will
receive multiple doses of RO7033877 first and 7 will receive multiple doses of
CMS first). In the second period, they will receive multiple doses of whichever
treatment they did not receive in Period 1 (either RO7033877 or CMS). They will
receive multiple doses of both RO7033877 and CMS together in the third period.

To date, one study has been carried out in healthy volunteers. A total of 52
healthy volunteers received single doses of up to 4.5 mg/kg and multiple doses
of up to 5 mg/kg twice a day of study medication. In addition, a study in
patients with renal impairment (kidney damage) and two studies in patients with
serious airway (lung) infections are ongoing.

The side effects seen in the study in healthy volunteers included the following:
* paresthesia, a sensation known as feeling numb or having *pins and
needles* (the most common)
* feeling dizzy
* gingivitis (inflammation and swelling around the teeth/gums)
* mouth ulcers
* eye irritation
* throat pain
* pain/irritation (reactions) at IV infusion site

The majority of the side effects were considered to be mild except for the
following:
* Three volunteers who had the dose administered once (single dose) had side
effects of moderate intensity: one had paresthesias (feeling numb or having
pins and needles); one had catheter site (IV infusion site) pain; and one
experienced dizziness and felt as if he might pass out (this feeling was
already present before the study drug was given).
* Five subjects who received multiple doses experienced the following side
effects: one had a moderate infusion site reaction; one had a catheter
site-related reaction; one had catheter site pain; one had a moderate feeling
of general weakness; and one had gingivitis