The PRIMO Study: Paricalcitol Capsules Benefits Renal Failure Induced Cardiac Morbidity in Subjects With Chronic Kidney Disease Stage 3/4

The PRIMO Study: Paricalcitol Capsules Benefits in Renal Failure Induced Cardiac Morbidity in Subjects With Chronic Kidney Disease Stage 3/4

To evaluate the effects of paricalcitol capsules on cardiac structure and function over 48 weeks in patients with Stage 3/4 chronic kidney disease (CKD) who had left ventricular hypertrophy (LVH).

Patients who met the inclusion criteria and did not meet any of the exclusion criteria were randomized in a 1:1 ratio to each treatment group to receive paricalcitol capsules or placebo. A stratified randomization scheme was used to ensure balance among treatment groups with respect to country, gender, and baseline renin angiotensin-aldosterone system (RAAS) inhibitor use (yes/no).

Participants who completed the 48-Week Treatment Period could continue on in the ongoing Long-term Follow-up Period that was to last 18 months, with study visits at 6 months, 12 months and 18 months post Treatment Week 48 Visit. Participants did not receive study drug, nor were they to have undergone echocardiogram/MRI procedures during the Long-term Follow-up Period.

Inclusion Criteria:

• Estimated glomerular filtration rate (GFR) between 15-60 mL/min/1.73 m^2

• Serum intact parathyroid hormone (iPTH) value between 50-300 pg/mL

• Corrected serum calcium level 8.0-10.0 mg/dL (2.0-2.5 mmol/L)

• Phosphorous level less than or equal to 5.2 mg/dL (1.68 mmol/L)

• Serum albumin greater than or equal to 3.0 g/dL (30 g/L)

• Echocardiogram results of:

  • Females: Left ventricular (LV) ejection fraction greater than or equal to 50% and septal wall thickness between 11-17 mm; and,
  • Males: LV ejection fraction greater than or equal to 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. However, the subject may have switched to different brands but at equivalent doses as determined by the study physician during the month prior to the Screening Period.

• Subject must have a technically adequate baseline cardiac magnetic resonance imaging (MRI).

Exclusion Criteria:

• Subject has previously been on active vitamin D therapy within the four weeks prior to the Screening Period
• Pregnant or lactating females
• Subject is expected to initiate renal replacement therapy within one year
• Subject is taking calcitonin, bisphosphonates, cinacalcet, glucocorticoids (except topical or inhaled glucocorticoids)
• Subject had clinically significant coronary artery disease (CAD) within 3 months prior to the Screening Period, defined as either hospitalization for myocardial infarction (MI) or unstable angina; new onset angina with positive functional study or coronary angiogram revealing stenosis; or coronary revascularization procedure.
• Subject had major cardiac valve abnormality linked with LVH and/or diastolic dysfunction, defined as either aortic valve area ≤ 1.5 cm^2 or a mean gradient of > 20 mmHg; or regurgitation lesions; more than moderate mitral regurgitation, or more than moderate aortic regurgitation.
• Subject had asymmetric septal hypertrophy defined as septal wall thickness/posterior wall thickness ratio > 1.5 based on screening echocardiogram.
• Subject had a severe cerebrovascular accident (CVA) within the last 3 months (e.g., hemorrhagic) prior to screening.
• Subject had full remission from a malignancy for less than 1 year except completely excised non-melanoma skin cancer (e.g., basal or squamous carcinoma) or any history of bone metastasis.
• Subject had comorbid conditions (e.g., advanced malignancy, advanced liver disease) with a life expectancy less than 1 year.