A Two-Part, Randomized, Placebo and Active-Controlled, Double-Blind, Thorough QT Study Evaluating the Effects of Intravenous Exenatide on Cardiac Repolarization in Healthy Male and Female Volunteers.

Part A Pilot:
ITCA 650 is a new device, developed by Intracia, to administer exenatide.
Exenatide is a drug that is used for the treatment of type 2 diabetes mellitus
(T2DM). Exenatide is a compound that is similar to a human hormone
(glucagon-like peptide-1, GLP-1). This hormone works by increasing insulin
production with increasing glucose levels in blood and delays the gastric
emptying of the stomach and decreases appetite. Exenatide is no new drug; it is
already available in the market under several dosages and formulations. In this
study the new device will not be used, but it is necessary for the further
development of the device.

Part B:
ITCA 650 is a new device, developed by Intracia, to administer exenatide
continuously over a period of up to 12 months. Exenatide is a drug that is used
for the treatment of diabetes mellitus type 2. Exenatide is a compound that is
similar to a human hormone (glucagon-like peptide-1, GLP-1). This hormone works
by increasing insulin production of the body with increasing glucose levels in
blood and delays the gastric emptying of the stomach and decreases appetite.
Exenatide is no new drug; it is already available in the market under several
dosages and formulations. In this study the new device will not be used, but it
is necessary for the further development of the device.

Part A Pilot:
The purpose of Part A is to investigate how quickly and to what extent
exenatide is absorbed and eliminated from the body and whether the plasma
levels of exenatide will reach the levels seen in patients with renal
impairment. It will also be investigated how safe the administration of
exenatide, when administered as a continuous IV infusion of 6 hours, is and how
well it is tolerated.

Part B:
The prupose of Part B is to evaluate if there is a prolongation of the
so-called QT interval; the QT interval is an ECG variable. When the QT interval
is prolonged, repolarization is delayed. This means that cardiac cells need
more time to prepare for the next beat. When a new heartbeat is about to start
and not all cardiac cells are prepared for that, arrhythmias may develop.

Part A Pilot:
The actual study will consist of 1 period during which you will stay in the
clinical research center in Groningen for 4 days (3 nights).
During the study you the volunteer will receive exenatide as a continuous
6-hour IV infusion. 30 minutes before the start of the IV infusion, you will
receive an IV administration of palonosetron.

Initially 2 volunteers will receive the study compound with the start time of
the infusion for the second volunteer 2 hours after the start of the first
infusion, if deemed safe by the research physician. If the infusion was well
tolerated and safe a similar process will be followed on the second day with 2
hours between the start of the administration to the third and fourth
volunteer. If the infusion was tolerated well by the third volunteer further
volunteers will receive the study compound with shorter intervals.

Part B:
The actual study will consist of 3 periods during which the volunteer will stay
in the clinical research center in Groningen for 4 days (3 nights) during the
first period and for 3 days (2 nights) during the second and third period. The
time interval between the different periods is 7 days between 2 study compound
administrations.
During the study the volunteer will receive exenatide or placebo as a
continuous 6-hour IV infusion. 30 minutes before the start of the IV infusion,
the volunteer will receive an IV administration of palonosetron.

Part A:
The study will consist of 1 period during which 0.406 µg/kg exenatide will be
given as a continuous IV infusion of 6 hours. For the second group the dose can
be adjusted if the target exposure has not been reached.

Part B:
The study will consist of 3 periods during which the subject will receive
exenatide once and placebo twice. Exenatide and placebo will be given as a
continuous IV infusion of 6 hours during each period.

During 1 of the placebo periods the subject will also receive moxifloxacin.
Moxifloxacin will be given as a 400 mg oral tablet. The subject will also
receive a single IV injection of palonosetron 30 minutes before the start of
the infusion of the study compound in each study period.

Pain, minor bleeding, bruises and possible infection.