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

Chronic Kidney Disease Clinical Trial

— VITAL  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00421733
• Other study ID #: M05-741
• Secondary ID: 2006-001363-31
• Status: Completed
• Phase: Phase 2
• First received: January 10, 2007
• Last updated: January 18, 2012
• Start date: December 2006
• Est. completion date: June 2009

Study information

• Verified date: January 2012
• Source: Abbott
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 281
• Est. completion date: June 2009
• Est. primary completion date: June 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Albuminuria
• Chronic Kidney Disease
• Diabetic Nephropathies
• Diabetic Nephropathy
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

Drug:
• Zemplar (paricalcitol ) capsules
Group 2 - paricalcitol 1 mcg capsules once daily (one paricalcitol 1 mcg capsule once daily and one matching placebo capsule once daily)
• Zemplar (paricalcitol) capsules
Group 3 - paricalcitol 2 mcg capsules once daily (two paricalcitol 1 mcg capsules once daily)
• Placebo
Group 1 - Placebo once daily (two placebo capsules once daily)

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Abbott

Countries where clinical trial is conducted

United States,  Germany,  Greece,  Italy,  Netherlands,  Poland,  Portugal,  Puerto Rico,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No