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

Phase 2

Completed

Conditions: Diabetic Nephropathy
Chronic Kidney Disease

Interventions: Drug: Zemplar (paricalcitol ) capsules
Drug: Zemplar (paricalcitol) capsules
Drug: Placebo

Registration Number: NCT00421733

Lead Sponsor: Abbott

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 281

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Paricalcitol 1 mcg	Zemplar (paricalcitol ) capsules	One paricalcitol 1 mcg capsule and one matching placebo capsule per dose
Paricalcitol 2 mcg	Zemplar (paricalcitol) capsules	Two paricalcitol 1 mcg capsules per dose
Placebo	Placebo	Two placebo capsules per dose

Primary Outcome Measures

Name	Time	Method
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).	Baseline (within 1 week prior to first treatment) through 24 weeks of treatment	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.

Secondary Outcome Measures

Name	Time	Method
Number of Participants Achieving a 15% or Greater Reduction From Baseline to Last On-treatment Urine Albumin to Creatinine Ratio (UACR) Levels.	Baseline (within 1 week prior to first treatment) through 24 weeks of treatment	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.
Change From Baseline to the Last On-treatment Measurement in Albumin Levels Determined From 24-hour Urine Collection.	Baseline (within 1 week prior to first treatment) through 24 weeks of treatment	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.
Change From Baseline to the Last On-treatment Observation in Intact Parathyroid Hormone (iPTH) Levels.	Baseline (screening period) through 24 weeks of treatment	Change is mean change in picograms of iPTH per milliliter of serum.

Trial Locations

Locations (72): Site Reference ID/Investigator# 856
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Dallas, Texas, United States
Site Reference ID/Investigator# 7214
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Omaha, Nebraska, United States
Site Reference ID/Investigator# 6626
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Winston-Salem, North Carolina, United States
Site Reference ID/Investigator# 862
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Phoenix, Arizona, United States
Site Reference ID/Investigator# 869
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Indianapolis, Indiana, United States
Site Reference ID/Investigator# 6281
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Boston, Massachusetts, United States
Site Reference ID/Investigator# 7494
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San Antonio, Texas, United States
Site Reference ID/Investigator# 774
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San Antonio, Texas, United States
Site Reference ID/Investigator# 864
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Fountain Valley, California, United States
Site Reference ID/Investigator# 857
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Pembroke Pines, Florida, United States
Site Reference ID/Investigator# 6312
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Bergamo, Italy
Site Reference ID/Investigator# 6207
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Groningen, Netherlands
Site Reference ID/Investigator# 7298
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Rio Piedras, Puerto Rico
Site Reference ID/Investigator# 5111
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Madrid, Spain
Site Reference ID/Investigator# 6330
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L'Hospitalet de, Spain
Site Reference ID/Investigator# 10621
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Galdakao, Spain
Site Reference ID/Investigator# 6329
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Santander, Spain
Site Reference ID/Investigator# 2531
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Chicago, Illinois, United States
Site Reference ID/Investigator# 853
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Hudson, Florida, United States
Site Reference ID/Investigator# 3371
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Evanston, Illinois, United States
Site Reference ID/Investigator# 867
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Lauderdale Lakes, Florida, United States
Site Reference ID/Investigator# 8901
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West Palm Beach, Florida, United States
Site Reference ID/Investigator# 7113
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Roswell, Georgia, United States
Site Reference ID/Investigator# 854
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Rockville, Maryland, United States
Site Reference ID/Investigator# 859
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Brooklyn Center, Minnesota, United States
Site Reference ID/Investigator# 866
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Charlotte, North Carolina, United States
Site Reference ID/Investigator# 5203
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Szczecin, Poland
Site Reference ID/Investigator# 7495
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Carlisle, Pennsylvania, United States
Site Reference ID/Investigator# 6302
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Ludwigshafen, Germany
Site Reference ID/Investigator# 5167
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Hannover, Germany
Site Reference ID/Investigator# 6314
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Athens, Greece
Site Reference ID/Investigator# 6316
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Duesseldorf, Germany
Site Reference ID/Investigator# 6306
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Ioannina, Greece
Site Reference ID/Investigator# 5631
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Thessaloniki, Greece
Site Reference ID/Investigator# 6310
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Thessaloniki, Greece
Site Reference ID/Investigator# 6303
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Brescia, Italy
Site Reference ID/Investigator# 6210
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Modena, Italy
Site Reference ID/Investigator# 6309
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Milan, Italy
Site Reference ID/Investigator# 6304
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Bydgoszcz, Poland
Site Reference ID/Investigator# 5622
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Katowice, Poland
Site Reference ID/Investigator# 6327
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Lisbon, Portugal
Site Reference ID/Investigator# 6315
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Warsaw, Poland
Site Reference ID/Investigator# 6916
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Caguas, Puerto Rico
Site Reference ID/Investigator# 6326
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Porto, Portugal
Site Reference ID/Investigator# 6290
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Las Piedras, Puerto Rico
Site Reference ID/Investigator# 5175
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Carolina, Puerto Rico
Site Reference ID/Investigator# 6300
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Ponce, Puerto Rico
Site Reference ID/Investigator# 6288
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San Juan, Puerto Rico
Site Reference ID/Investigator# 5170
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San Juan, Puerto Rico
Site Reference ID/Investigator# 6569
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Barcelona, Spain
Site Reference ID/Investigator# 6286
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Hsin-Chuang City, Taiwan
Site Reference ID/Investigator# 8335
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Taichung City, Taiwan
Site Reference ID/Investigator# 6294
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Taipei City, Taiwan
Site Reference ID/Investigator# 11281
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Valencia, Spain
Site Reference ID/Investigator# 7927
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Taichung, Taiwan
Site Reference ID/Investigator# 8039
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Greenville, North Carolina, United States
Site Reference ID/Investigator# 7291
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Yuba City, California, United States
Site Reference ID/Investigator# 8054
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Baton Rouge, Louisiana, United States
Site Reference ID/Investigator# 8046
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Albany, New York, United States
Site Reference ID/Investigator# 8053
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Morehead City, North Carolina, United States
Site Reference ID/Investigator# 5110
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Oviedo, Spain
Site Reference ID/Investigator# 9061
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Dallas, Texas, United States
Site Reference ID/Investigator# 8325
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Dallas, Texas, United States
Site Reference ID/Investigator# 7509
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San Juan, Puerto Rico
Site Reference ID/Investigator# 5179
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Ponce, Puerto Rico
Site Reference ID/Investigator# 5168
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Ponce, Puerto Rico
Site Reference ID/Investigator# 6919
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Toa Baja, Puerto Rico
Site Reference ID/Investigator# 6285
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Taipei, Taiwan
Site Reference ID/Investigator# 6293
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Ponce, Puerto Rico
Site Reference ID/Investigator# 6291
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San Juan, Puerto Rico
Site Reference ID/Investigator# 5173
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Ponce, Puerto Rico
Site Reference ID/Investigator# 6296
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Yabucoa, Puerto Rico