A Phase 1 randomized, double-blind study to investigate the single and multiple dose safety, tolerability and pharmacokinetics of WCK 4282 (FEP-TAZ) upon intravenous administrations in healthy volunteers

The study drug is WCK 4282 (FEP-TAZ), Wockhardt*s proprietary injectable,
antibacterial combination product consisting of cefepime (FEP) and tazobactam
(TAZ).

Part 1
To evaluate the safety, tolerability, and pharmacokinetics (PK) of multiple
intravenous doses of FEP-TAZ 4 g (2 g cefepime + 2 g tazobactam) and FEP-TAZ 3
g (2 g cefepime + 1 g tazobactam) administered every 8 hours (q8h) in healthy
adult volunteers for 10 days.

Part 2
To evaluate the safety, tolerability, and pharmacokinetics (PK) of single
intravenous doses of FEP-TAZ 4 g (2 g cefepime + 2 g tazobactam), 2 g of
cefepime and 2 g of tazobactam administered in healthy adult volunteers.

This study is a 2 part study in healthy adult subjects to be conducted in a
single center.
Part 1 is a randomized, double-blind, placebo controlled, multiple intravenous
dose study.
Part 2 is a double-blind, single intravenous dose, randomized, three period
cross-over study with a washout of at least 96 hours (maximum 98 hours) between
successive dosing occasions and after last dose.

The study will start with a screening visit. During the screening visit
standard medical assessments including safety laboratory tests (blood draw,
urine collection), an alcohol breath test, urine drug screen, a physical
examination, ECG and a vital signs measurement will be performed.

During study the subjects will enter the clinic, will receive medication as a
q8h regimen for 10 days (part 1) or three single doses on three different days
(part 2). They will be asked on a regular basis for possible side effects,
blood will be drawn for safety and PK measurements, urine will be collected for
safety and PK measurements and vital signs and ECG will bechecked regularly
during the confinement period.

Finally a follow-up examination will be performed. During this visit the
subjects will be asked for possible side effects, blood will be drawn for
safety, the vital signs/ECG will be checked and a physical examination will be
conducted.

Cefepime and Tazobactam have each been on the market for approximately 20
years. Both the compounds have been extensively evaluated in animal and human
trials.

Cefepime: The most frequently reported side effects observed in multiple dose
trials were: local reactions including inflammation of a vein, local reactions
of pain and/or inflammation, rash, diarrhea, nausea, vomiting, itching, fever
and headache.

Tazobactam: The most frequently reported side effects observed in multiple dose
trials were: diarrhea, headache, constipation, nausea, insomnia, rash,
vomiting, upset stomach, itching, stool changes, fever, restlessness,
candidiasis, hypertension, dizziness, abdominal pain, chest pain, edema,
anxiety, rhinitis and shortness of breath.

Recently, 12 volunteers participated in the first part of this clinical trial.
The following side effects have been reported by the 10 of the 12 volunteers:
infusion site reaction (tenderness and erythema at the infusion site, and
redness of the skin), increased white blood cell counts, loose stool, abdominal
pain and an increased body temperature. The reported side effects were mild to
moderate in intensity. The infusion site reactions were most likely caused by
the low quantity of diluent in which the study drug was dissolved. To prevent
these infusion site reactions in this trial, the quantity of the diluent in the
final formulation has been increased.

The blood collection procedure is not dangerous, but may cause discomfort or
bruising. Occasionally, fainting, bleeding or an infection at the blood
sampling site can occur.