Oral Paricalcitol in Stage 3 - 5 Chronic Kidney Disease
Oral Paricalcitol in Stage 3 - 5 Chronic Kidney Disease
The purpose of this study is to test the hypothesis that selective vitamin D receptor
 activation reduces left ventricular hypertrophy and ameliorates inflammation and
 atherosclerosis in stage 3 -5 chronic kidney disease.
Cardiovascular disease is the leading cause of mortality and morbidity in patients with
 chronic kidney disease. According to a previous study, only 15.6% of the patients beginning
 dialysis therapy had a normal echocardiogram, with left ventricular hypertrophy, left
 ventricular dilatation and systolic dysfunction occurring in 40.7%, 28% and 15.6% of
 patients, respectively. In addition, these patients are at an accelerated risk of developing
 atherosclerosis. The Kidney Disease Outcome Quality Initiative guideline recently raised
 concerns of a high prevalence of vitamin D deficiency in chronic kidney disease patients not
 yet requiring dialysis treatment. In addition, very recent data suggested that vitamin D
 deficiency is an important predictor of mortality in end-stage renal disease patients.
 Furthermore, hemodialysis patients treated with paricalcitol, a selective vitamin D receptor
 activator, showed a significantly lower risk of cardiovascular death than those not receiving
 vitamin D therapy. A number of studies also showed positive benefit of vitamin D receptor
 activator treatment on regression of left ventricular hypertrophy in dialysis patients.
 However, there is so far no data in patients with stage 3 and 4 chronic kidney disease where
 a high prevalence of vitamin D deficiency and cardiac hypertrophy has been reported.
Inclusion Criteria:

 -  Patient with stage 3 -5 chronic kidney disease (that is, eGFR < 60 ml/min per 1.73m2)
 diagnosed for more than 2 months and not expected to start dialysis within the next 12
 months, and

 -  Patient with screening echocardiography showing evidence of left ventricular
 hypertrophy

 -  Patient has not received vitamin D therapy in the previous 4 weeks

 -  For entry into the Treatment Phase, the subject must have:

 -  screening iPTH >= 55 pg/ml or 5.8pmol/L (determined by the Nichols
 second-generation assay or similar assay)

 -  serum calcium < 10.2 mg/dL (2.55 mmol/L)

 -  serum phosphorus =< 5.2mg/dL (1.68mmol/L)

 -  Ca*P product < 54 mg2/dL2 (4.36mmol2/L2)

 -  If female, subject is either not of childbearing potential, defined as
 postmenopausal for at least 1 year or surgically sterile (bilateral tubal
 ligation, bilateral oophorectomy, or hysterectomy), or is of childbearing
 potential and practicing birth control measures.

 -  Patients who provide informed consent for the study

 Exclusion Criteria:

 -  Patient with a history of an allergic reaction or significant sensitivity to vitamin D
 or vitamin D related compounds.

 -  Patient with history of renal stones

 -  Patient with current malignancy

 -  Patients with clinically significant gastrointestinal disease or liver disease

 -  Patient with acute renal failure in the recent three months

 -  Patient with a history of drug or alcohol abuse within six months prior to the
 screening phase

 -  Patient is known to be human immunodeficiency virus (HIV) positive.

 -  Patient with evidence of poor compliance with diet and medication.

 -  Patient currently receiving medications that may affect calcium, phosphorus metabolism
 such as calcitonin, cinacalcet, bisphophonates or vitamin D compounds (other than
 study drug), or other drugs that may affect calcium or bone metabolism, other than
 females on stable estrogen and/or progestin therapy.

 -  Patients with active granulomatous disease

 -  Patient with pregnancy

 -  Patients currently receiving glucocorticoid steroid or other immunosuppressive
 treatment or had been administered glucocorticoid or other immunosuppressive treatment
 for more than 14 days within recent 6 months.

 -  Patients with contraindication for MRI examination