The PRIMO II Study: Paricalcitol Injection Benefits in Renal Failure Induced Cardiac Morbidity in Subjects With Chronic Kidney Disease (CKD) Stage 5
Condition: Chronic Kidney Disease (CKD) Stage 5; Hypertrophy, Left Ventricular
MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Renal Insufficiency; Hypertrophy, Left Ventricular; Hypertrophy
Intervention: paricalcitol injection 4 mcg/mL; Placebo Injection 4 mcg/mL
Intervention description: Paricalcitol Injection 4 mcg/mL intravenously three times a week during dialysis; Placebo Injection 4 mcg/mL given intravenously three times a week during dialysis
Intervention MeSH terms: Ergocalciferols
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 12.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Zemplar, paricalcitol, PRIMO II

Summary:

      To evaluate the effects of paricalcitol injection on cardiac structure and function over 48
      weeks in subjects with Stage 5 Chronic Kidney Disease (CKD) receiving hemodialysis who have
      left ventricular hypertrophy (LVH).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Stage 5 CKD receiving chronic hemodialysis three times per week for >= 3 months and <=
             12 months from date of Randomization (Day 1).

          -  Serum intact parathyroid hormone (iPTH) value between 100-350 pg/mL.

          -  Serum calcium level between 8.4-10.5 mg/dL (2.1-2.6 mmol/L).

          -  Phosphate < 7 mg/dL.

          -  Serum albumin >= 3.0 g/dL (30 g/L).

          -  Echocardiogram results:

               -  For females, left ventricular (LV) ejection fraction >= 50% and septal wall
                  thickness between 11-17 mm.

               -  For males, LV ejection fraction >= 50% and septal wall thickness between 12-18
                  mm.

          -  If the subject is receiving Renin Angiotensin-Aldosterone System (RAAS) inhibitors,
             the dose must have been stable for greater than one month prior to the Screening
             Period.

          -  A technically adequate baseline cardiac magnetic resonance imaging (MRI).

          -  If female, subject is not breast feeding or is not pregnant, or is not of childbearing
             potential, defined as postmenopausal for at least one year or surgically sterile, or
             is of childbearing potential and practicing one of the following methods of birth
             control:

          -  Double-barrier method

          -  Hormonal contraceptives for at least three months prior to and during study drug
             administration

          -  Maintains a monogamous relationship with a vasectomized partner

          -  Total abstinence from sexual intercourse during the study.

        Exclusion Criteria:

          -  Subject has previously been on active vitamin D therapy (calcitriol, paricalcitol,
             doxercalciferol, alfacalcidol) for a total duration greater than three months since
             the start of dialysis.

          -  Subject has a history of an allergic reaction or significant sensitivity to
             paricalcitol or to drugs similar to the study drug.

          -  Subject is expected to receive an increased dose of RAAS inhibitor (Angiotensin
             converting enzyme inhibitor [ACEi], Angiotensin II receptor blocker [ARB] or
             aldosterone inhibitor) during the course of the study.

          -  Subject has clinically significant coronary artery disease (CAD) within 3 months prior
             to the Screening Period, defined as one of the following:

               -  Hospitalization for myocardial infarction (MI) or unstable angina; or

               -  New onset angina with positive functional study or coronary angiogram revealing
                  stenosis; or

               -  Coronary revascularization procedure.

          -  Subject has major cardiac valve abnormality linked with left ventricular hypertrophy
             (LVH) and/or diastolic dysfunction, defined as one of the following:

               -  Aortic valve area <= 1.5 cm2 or a mean gradient of > 20 mmHg; or

               -  Regurgitation lesions; more than moderate mitral regurgitation or more than
                  moderate aortic regurgitation.

          -  Subject has asymmetric septal hypertrophy.

          -  Subject has had a severe cerebrovascular accident (CVA) within the last three months
             (e.g., hemorrhagic) prior to screening.

          -  Full remission from a malignancy for less than one year except completely excised
             non-Melanoma skin cancer (e.g. basal or squamous carcinoma) or any history of bone
             metastasis.

          -  Subject has co-morbid conditions.

          -  Subject has received any investigational drug within 30 days prior to study drug
             administration or is currently enrolled in another clinical trial.

          -  Subject has poorly controlled hypertension.

          -  Subject has history of renal artery stenosis, primary aldosteronism or
             pheochromocytoma

          -  Subject is taking calcitonin, bisphosphonates, cinacalcet, glucocorticoids (except
             topical or inhaled glucocorticoids)

          -  Subject is currently receiving immunosuppressant therapy and/or high doses of
             glucocorticoids

          -  Subject is known to be HIV positive.

          -  Use of known inhibitors or inducers of cytochrome P450 3A (CYP3A) within two weeks
             prior to study drug administration

          -  Subject is contraindicated for the MRI examination

          -  Investigator considers subject unsuitable for any reason

          -  Subject has a history of drug or alcohol abuse within six months prior to screening

          -  Subject weighs more than 340 pounds (154 kg)

          -  Subject has had a liver transplant