The Effect of Paricalcitol Capsules on Reducing Albuminuria in Patients With Type 2 Diabetic Nephropathy Being Treated With Renin-angiotensin System Inhibitors

Study Overview
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Brief Summary
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The study objective was to evaluate the safety of paricalcitol capsules and the efficacy of paricalcitol capsules for albuminuria reduction in patients with Chronic Kidney Disease (CKD) who have Type 2 diabetic nephropathy and are receiving optimal angiotensin converting enzyme (ACE) inhibitor and/or angiotensin II receptor blocker (ARB) therapy.

Official Title
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VITAL Study - Selective VITamin D Receptor Activator (Paricalcitol) for Albuminuria Lowering Study: A Phase 2, Prospective, Randomized, Double-blind, Placebo-Controlled, Multicenter Study to Evaluate the Safety and Efficacy of Paricalcitol Capsules on Reducing Albuminuria in Type 2 Diabetic Nephropathy Subjects Who Are Currently Being Treated With Renin-angiotensin System Inhibitors

Conditions
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Diabetic Nephropathy, Chronic Kidney Disease

Intervention / Treatment
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* Drug: Zemplar (paricalcitol ) capsules
* Drug: Zemplar (paricalcitol) capsules
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female participant >= 20 years old. Participant has Type 2 Diabetes Mellitus and has been treated with at least one anti-hyperglycemic medication within the 12 months prior to the Screening Phase Participant has been receiving a stable dose (i.e., same type and regimen) of ACEi and/or ARB for at least three months prior to the Screening Phase. However, participant may have switched to different brands but at equivalent doses during the three months prior to the Screening Phase. Participant is not expected to begin dialysis for at least 6 months. If female, participant is not breast feeding or is not pregnant. For entry into the Treatment Phase, the participant must satisfy the following criteria based on the Screening laboratory values: Estimated glomerular filtration rate (GFR) between 15-90 mL/min/1.73m2 by simplified Modification in Diet in Renal Disease (MDRD) formula Urinary albumin to creatinine ratio (UACR) between 100 and 3000 mg/g as determined by the mean of the three first morning void urine specimens obtained within one week of each other Corrected serum calcium level <= 9.8 mg/dL intact parathyroid hormone (iPTH) value between 35-500 pg/mL Glycosylated hemoglobin A1c (HbA1c) <= 12% Serum albumin > 3.0 g/dL Negative urine pregnancy test for female participants Exclusion Criteria: Participant has previously been on prescription-based vitamin D therapy within the six months prior to the Screening Phase. Participant has a history of an allergic reaction or significant sensitivity to paricalcitol or to drugs similar to the study drug. Participant has primary glomerulonephritis or secondary nephritis in addition to diabetic nephropathy. Participant has had acute renal failure within 12 weeks of the Screening Phase, defined as an acute rise (of >= 0.5 mg/dL) in serum creatinine to > 4 mg/dL. Participant has chronic gastrointestinal disease. Participant has secondary hypertension. Participant has poorly controlled hypertension. Participant has a history of kidney stones. Participant has a history of drug or alcohol abuse within six months prior to the Screening Phase. Participant has evidence of poor compliance with diet or medication. Participant has received any investigational drug within 30 days prior to study drug administration. Participant is taking calcitonin, bisphosphonates, cinacalcet, glucocorticoids (except topical glucocorticoids), or other drugs that may affect calcium, or bone metabolism, other than calcium containing phosphate binder or female participants on stable (same dose and product for three months) estrogen and/or progestin therapy. For any reason, participant is considered by the Investigator to be an unsuitable candidate to receive paricalcitol capsules or is put at risk by study procedures. Participant is known to be human immunodeficiency virus (HIV) positive. Participant has used known inhibitors or inducers of cytochrome P450 3A (CYP3A) within two weeks prior to study drug administration.

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Paricalcitol 1 mcg<br>One paricalcitol 1 mcg capsule and one matching placebo capsule per dose | Drug: Zemplar (paricalcitol ) capsules<br>* Group 2 - paricalcitol 1 mcg capsules once daily (one paricalcitol 1 mcg capsule once daily and one matching placebo capsule once daily)<br>* Other names: Zemplar;|
| Active Comparator: Paricalcitol 2 mcg<br>Two paricalcitol 1 mcg capsules per dose | Drug: Zemplar (paricalcitol) capsules<br>* Group 3 - paricalcitol 2 mcg capsules once daily (two paricalcitol 1 mcg capsules once daily)<br>* Other names: Zemplar;|
| Placebo Comparator: Placebo<br>Two placebo capsules per dose | Drug: Placebo<br>* Group 1 - Placebo once daily (two placebo capsules once daily)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to the Last On-treatment Measurement in Urine Albumin to Creatinine Ratio (UACR) Levels Determined From the First Morning Void (FMV) Urine Collections Comparing Placebo to the Combined Paricalcitol Treatment Groups (1 Mcg and 2 Mcg). | UACR is defined as the ratio: milligram of albumin per gram of creatinine. Baseline UACR was determined as the mean of the 3 UACR measurements from FMV urine collections obtained within 1 week prior to the day of the first dose of study drug. The last on-treatment measurement was the mean of the 3 UACR measurements obtained from FMV urine collections obtained within 1 week of the final week of treatment. The UACR data were log transformed prior to analysis. | Baseline (within 1 week prior to first treatment) through 24 weeks of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Achieving a 15% or Greater Reduction From Baseline to Last On-treatment Urine Albumin to Creatinine Ratio (UACR) Levels. | Number of participants whose last on-treatment albumin to creatinine ratio (UACR) value was reduced at least 15% from the baseline value. Albumin values were determined from 24-hour urine collections from the baseline and last on-treatment visits. | Baseline (within 1 week prior to first treatment) through 24 weeks of treatment | 
| Change From Baseline to the Last On-treatment Measurement in Albumin Levels Determined From 24-hour Urine Collection. | The change is mean change from baseline to the last on-treatment value, with the data being log transformed prior to analysis. Albumin values were determined from 24-hour urine collections from the baseline and last on-treatment visits. | Baseline (within 1 week prior to first treatment) through 24 weeks of treatment | 
| Change From Baseline to the Last On-treatment Observation in Intact Parathyroid Hormone (iPTH) Levels. | Change is mean change in picograms of iPTH per milliliter of serum. | Baseline (screening period) through 24 weeks of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 2 Diabetic Nephropathy