Evaluation of Insuman Implantable 400 IU/ml in patients with Type 1 diabetes treated with the Medtronic MiniMed Implantable Pump System using Insuplant 400 IU/mL

Insulin therapy by implantable insulin pumps represents a unique mode of
insulin delivery. This mode of insulin administration results in lower plasma
insulin levels in the peripheral venous system than those obtained by
subcutaneous insulin delivery.
About 459 patients are currently treated with an implantable pump system using
Insuplant 400 IU/ml. However, the production of Insuplant 400 IU/mL has been
stopped and the last available Insuplant 400 IU/mL batches allow product
supplies until at the latest June 2011. Given the unmet clinical need in these
already implanted patients, sanofi aventis has developed an insulin
formulation; tradename Insuman Implantable 400 IU/ml) suitable for use in the
Medtronic Minimed implantable pump. Considering the medical need for the
already implanted patients, and in light of the CHMP (The Committee for
Medicinal Products for Human Use) request to provide in vivo data with Insuman
Implantable, sanofi-aventis has decided to set up a clinical program.

(1) To generate new clinical efficacy and safety data to support the
registration of Insuman Implantable 400 IU/ml,
(2) To ensure the continuation of the treatment of the patients already
implanted and avoid pump explantation, up to the approval of Insuman
Implantable 400 IU/ml.

The study duration will be displayed in 2 parts as follow:

Comparative phase (only French patients): 160 +/- 20 days

Open label Insuman Implantable extension phase (French and European patients):
from day 160 up to the grant of Insuman implantable marketing authorization

• Insuman Implantable 400 IU/mL
• Insuplant 400 IU/mL

Continuous Intraperitoneal insulin infusion: basal rate and boluses
• Medtronic minimed pump refill will be performed every 40 +/- 5 days

Side effects of insulin Implantable Insuman 400 IU / ml and Insuplant are
similar to those of all insulins. These effects are very common (more than a
patient in 10) and are mainly due to:
- hypoglycemia (low blood sugar) because of overdosing (sweating, pallor,
nervousness, tremor, tiredness, weakness, confusion, difficulty in
concentrating, dizziness, increased appetite, headache, nausea and increased
heart beat) - hyperglycemia (high blood sugar) due to underdosing (thirst,
increased urination, dehydration, "fruity" odor of the breath or urine,
tiredness and difficulties in thinking).

Local reactions at the infusion points are possible (may occur): itching,
unusual pain, redness, hives or inflammation. A thickening or thinning of the
skin may also occur at the injection site.

Allergic reactions to insulin or solution that contains it are rare; they can
be associated with generalized skin reactions and may rarely lead to a
life-threatening shock. Rarely, insulin may induce sodium retention and oedema,
and very rarely muscle pain. Moreover, despite the beneficial effect of
long-term stability of blood glucose on the progression of retinopathy (eye
diabetic disease), a significant change in blood sugar can cause a temporary
decrease in vision.

Treatment with insulin can lead to the formation in the body of anti-insulin
antibodies (substances
that act against insulin).