EValuation Of Cinacalcet HCL Therapy to Lower CardioVascular Events

In this study, the study medication cinacalcet is evaluated for the treatment
of patients with CKD with secondary HPT on dialysis. This study will include a
total of approximately 3800 subjects from approximately 500 centers in North,
Central and South America; Australia; and Europe. Amgen Inc. (hereafter known
as *Amgen*), a for-profit drug company, is sponsoring and funding this clinical
study. The investigational product being tested in this research study is
called cinacalcet. Cinacalcet acts directly on the calcium-sensing receptors
on the surface of the parathyroid gland cells to increase the parathyroid
glands sensitivity to calcium levels. The European Committee for Medicinal
Products for Human Use (CHMP) has approved cinacalcet (Mimpara®; Parareg®) for
the treatment of secondary HPT in patients with CKD on dialysis as well as for
the treatment of hypercalcemia (high calcium) in patients with parathyroid
carcinoma (a cancer of the parathyroid gland).

Secondary HPT is common in people with CKD. Patients with secondary HPT often
have high PTH levels and may develop large parathyroid glands in the neck.
Patients with secondary HPT may have bone disease (osteodystrophy). This bone
disease may cause bone pain, fractures, and poor formation of red blood cells.
Other problems from secondary HPT may include increases in blood levels of
calcium and phosphorus. These may cause calcium to deposit in body tissues.
Calcium deposits can cause arthritis (joint pain and swelling), muscle
inflammation, itching, gangrene (death of soft tissue), or heart and lung
problems. New evidence suggests that secondary HPT is associated with
cardiovascular disease and increased death risk. The purpose of this study is
to evaluate the effects of cinacalcet (or Mimpara®) on cardiovascular events
and death in chronic kidney disease patients with secondary HPT who are
receiving dialysis.

This is a multicentre, randomized, double-blind, phase 3 study. The study will
consist of a 30-day screening period followed by 2 consecutive phases
(periods): a dose-titration period (in this phase, your best dose is
determined) lasting 20 weeks with study visits every 2 weeks and a follow up
period with study visits every 8 weeks that will last approximately 4 years or
until Amgen notifies the sites that the study has been completed or terminated.
Subjects who qualify for the study will be randomized at a 1:1 ratio to the
following groups:
Group A: Cinacalcet (active)
Group B: Placebo (control group)
The inclusionperiod is from September 2006 till January 2008.

Cinacalcet is taken orally every day. The passible dose is cinacalcet or
placebo 30, 60, 90, 120 en 180 mg.

The total trial duration is expected to be approximately 4 years. The study
duration of an individual subject will depend on when the subject starts the
study: It is expected that the first subject enrolled into this study will be
followed for approximately 4 years and the last subject enrolled will be
followed for approximately 2.5 years. In these 4 years the patient will have
approximately 35 study visits, these visits will be planned (if possible) with
the patients regular dialysis visits. In general the visits consist of
reporting adverse events, concomitant medication, blood samples are taken for
various laboratory measurements and cinacalcet/placebo will be dispensed.

The most common side effects in subjects receiving cinacalcet were, nausea and
vomiting. In general, the episodes of nausea and vomiting did not require
treatment and subjects were able to complete the study.
One of the expected actions of cinacalcet is to reduce blood calcium levels.
Blood calcium levels will be monitored and appropriate action(s) will be taken
as necessary. Cinacalcet may affect the body*s ability to remove certain
medications. In addition, certain medications may affect the body*s ability to
remove cinacalcet. Therefore, the study doctor may need to adjust the dose of
medications. Patients will be monitored closely to minimize the risk of any
side effects.