The PRIMO Study: Paricalcitol Capsules benefits in Renal failure Induced cardiac Morbidity in Subjects with Chronic Kidney Disease Stage 3B/4 - PRIMO I
- Conditions
- Stage 3B/4 chronic kidney disease (CKD) in subjects who have left ventricular hypertrophy (LVH).MedDRA version: 9.1Level: LLTClassification code 10064848Term: Chronic kidney diseaseMedDRA version: 9.1Level: LLTClassification code 10049773Term: Left ventricular hypertrophy
- Registration Number
- EUCTR2007-001689-34-SE
- Lead Sponsor
- Abbott GmbH & Co. KG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 220
Subjects must meet all of the following criteria:
1. Subject has voluntarily signed and dated an informed consent form, approved by
an Institutional Review Board (IRB)/Independent Ethics Committee (IEC), after
the nature of the study has been explained and the subject has had the opportunity
to ask questions. The informed consent must be signed before any study-specific
procedures are performed.
2. Male or female subjects = 18 years.
3. For entry into the Treatment Period the subject must satisfy the following criteria
based on the Screening laboratory values:
? Estimated GFR between 15-60 ml/min/1.73 m2 by simplified 4-variable
Modification of Diet in Renal Disease (MDRD) formula (this includes a 10%
variation in the upper limit of eGFR that will be allowed for the enrollment of
subjects, this is to account for variability in the creatinine assay).
? Serum iPTH value between 50-300 pg/mL.
? Serum calcium level 8.0-10.0 mg/dL (2.0-2.5 mmol/L).
? Phosphorous level = 5.2 mg/dL (1.68 mmol/L).
? Serum albumin = 3.0 g/dL (30 g/L).
? Negative serum pregnancy test for female subjects of childbearing potential.
4. For entry into the Treatment Period the subject must satisfy the following criteria
based on the Screening echocardiogram:
? For females, LV ejection fraction = 50% and septal wall thickness between
11-17 mm; and,
? For males, LV ejection fraction = 50% and septal wall thickness between
12-18 mm.
5. If the subject is receiving RAAS inhibitors the dose must have been stable for
greater than one month prior to the Screening Period.
6. Subject must have a technically adequate baseline cardiac MRI.
7. If female, subject is not breast feeding or is not pregnant (verified by negative
pregnancy test prior to the Treatment Period); or is not of childbearing potential,
defined as postmenopausal for at least one year or surgically sterile (bilateral tubal
ligation, bilateral oophorectomy or hysterectomy); or is of childbearing potential
and practicing one of the following methods of birth control:
? Double-barrier method (any two of the following: condoms, contraceptive
sponge, diaphragm, vaginal ring with spermicidal jellies or creams, or
intrauterine device [IUD])
? Hormonal contraceptives (oral, parenteral, or transdermal) 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 (minimum
one complete menstrual cycle prior to study start)
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
Subjects must not meet any of the following criteria:
1. Subject has previously been on active vitamin D therapy (calcitriol, paricalcitol,
doxercalciferol, alfacalcidol) within the four weeks prior to the Screening Period.
2. Subject has a history of an allergic reaction or significant sensitivity to paricalcitol
or to drugs similar to the study drug (i.e., vitamin D or vitamin D related
compounds).
3. Pregnant (confirmed by screening pregnancy test) or lactating females.
4. Subject is expected to initiate renal replacement therapy within one year.
5. Subject is expected to receive an increased dose of RAAS inhibitor (ACEi, ARB
or aldosterone inhibitor) during the course of the study.
6. Subject has clinically significant coronary artery disease (CAD) within 3 months
prior to the Screening Period, defined as one of the following:
? Hospitalization for MI or unstable angina; or
? New onset angina with positive functional study or coronary angiogram
revealing stenosis; or
? Coronary revascularization procedure.
7. Subject has major cardiac valve abnormality linked with LVH and/or diastolic
dysfunction, defined as one of the following:
? Aortic valve area = 1.5 cm2 or a mean gradient of > 20 mm Hg; or
? Regurgitation lesions; more than moderate mitral regurgitation or more than
moderate aortic regurgitation.
8. Subject has asymmetric septal hypertrophy defined as septal wall
thickness/posterior wall thickness ratio > 1.5 based on screening echocardiogram.
9. Subject has had a severe cerebrovascular accident (CVA) within last 3 months
(e.g. hemorrhagic) prior to screening.
10. 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.
11. Subject has co-morbid conditions (e.g., advanced malignancy, advanced liver
disease) with a life expectancy less than 1 year.
12. Subject has received any investigational drug within 30 days prior to study drug
administration or is currently enrolled in another clinical trial.
13. Subject has a history of active kidney stones within the 2 years prior to the
Screening Period.
14. Subject has poorly controlled hypertension (systolic blood pressure > 180 mmHg
and/or diastolic blood pressure > 110 mmHg) at the Screening Visit (confirmed by
repeat).
15. Subject has history of renal artery stenosis, primary aldosteronism or
pheochromocytoma.
16. Subject is taking calcitonin, bisphosphonates, cinacalcet, glucocorticoids (except
topical or inhaled glucocorticoids), or other drugs that may affect calcium or bone
metabolism, other than aluminum, calcium and non-calcium containing phosphate
binders or female subjects on stable (same dose and product for three months)
estrogen and/or progestin therapy.
17. Subject is currently receiving immunosuppressant therapy and/or high doses
(non-maintenance therapy) of glucocorticoids (> 5 mg/day of prednisone or
equivalent).
18. Subject has had acute renal failure within 12 weeks of the Screening Phase defined
by an acute rise in serum Cr (of at least 0.5 mg/dL or 44 micromoles/L) to more
than 4 g/dL (350 micromoles/L).
19. Subject is known to be HIV positive.
20. Use of known inhibitors (i.e., ketoconazole) or inducers (i.e., carbamazepine) of
cytochrome P450 3A (CYP3A) within two weeks prior to study drug
administration.
21. Subject is contraindicated for the MRI examination (i.e., pacemaker).
22. For any reason, subject is considered by the Investigator t
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method