A phase 1, randomized, placebo-controlled study to assess the safety and pharmacokinetics of multiple ascending dose regimens of TP-6076.

TP-6076 is a new investigational compound that may eventually be used for the
treatment of infections with bacteria for which other antibiotics don*t work
anymore. TP-6076 is a tetracycline. Tetracyclines are a group of antibiotics
that were used a lot for specific infections (urinary tract,
airway and intestinal infections), but that can be used less and less as a
result of the development of resistance in the bacteria. Tetracyclines like
TP-6076 block the function of certain enzymes in the bacteria.TP-6076 is in
development and is not registered as a drug, but has been given to humans
before.

The purpose of the study is to investigate how safe TP-6076 is and how well
TP-6076 is tolerated. It will also be investigated how quickly and to what
extent TP-6076 is absorbed and eliminated from the body (this is called
pharmacokinetics). This study will be performed in 56 healthy male and female
volunteers, divided over a maximum of 7 groups.

The actual study will consist of 1 period during which the volunteer will stay
in the clinical research center in Groningen (location Martini Hospital) for 12
days (11 nights). They are expected at the clinical research center at 14:00 h
in the afternoon prior to the first day of administration of the study
compound. They will be required not to have consumed any food or drinks during
the 4 hours prior to arrival in the clinical research center (with the
exception of water). The volunteer will leave the clinical research center on
Day 11 (Day 1 is the first day of administration of the
study compound). The follow-up visit will take place between Day 13 and Day 16
of the study. The appointment for the follow-up visit will be made during the
study. The participation to the entire study, from the pre-study screening
until the follow-up visit, will be a maximum of 46 days (approximately 6.5
weeks).

During the study the volunteer will receive TP-6076 or placebo as an iv
infusion of 30 minutes (in groups 1-3) or 60 minutes (group 4) under fasted
conditions. This means that they are not allowed to eat for at least 10 hours
before administration of the study compound. During fasting they are allowed to
drink water with the exception of 2 hours prior to until 1 hour after
administration of the study compound. They will receive a breakfast 30 minutes
after the end of each iv infusion.

Group 1; Day 1 to 7 TP-6076 6.0 mg or placebo; once daily
Group 2; Day 1 to 7 TP-6076 20.0 mg or placebo; once daily
Group 3; Day 1 to 7 TP-6076 40.0 mg or placebo; once daily
Group 4; Day 1 to 7 TP-6076 60.0 mg or placebo; once daily
Group 5; Day 1 TP-6076 40.0 mg or placebo; once daily
Group 5; Day 1 to 7 TP-6076 20.0 mg or placebo; twice daily

Treatment for Group 6 and 7 will be decided based on the results from previous
groups. You will be informed about the amount and frequency of the study
compound administration after you entered the clinical research center. The
treatment will be within the ranges as described below.

Pain, minor bleedings, bruises, possibly an infection.

The study compound is a tetracycline. The following adverse effects are known
for tetracyclines, although they are not reported very often:
Nausea, vomiting, photosensitivity (therefore you are not allowed to stay in
the sun), increased intracranial pressure, pancreatitis, allergic reactions,
abdominal pain, headache, loss of appetite, visual changes, increased frequency
of urination or amount of urine, increased thirst, unusual tiredness or
weakness, pigmentation (darker color or discoloration) of skin, bone and teeth,
cramps or burning of the stomach, diarrhea, change in stool color, sore mouth
or tongue, dizziness, light-headedness and unsteadiness, , and pain, swelling
and irritation at the infusion site.