Clinical trial NCT00421733: The Effect of Paricalcitol Capsules on Reducing Albuminuria in Patients With Type 2 Diabetic Nephropathy Being Treated With Renin-angiotensin System Inhibitors
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diabetic Nephropathy
Chronic Kidney Disease
Keywords: Type 2 Diabetic Nephropathy
Lead sponsor: Abbott
Sponsor class: INDUSTRY
First posted: 2007-01-12
Enrollment: 281
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: 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).
timeFrame: Baseline (within 1 week prior to first treatment) through 24 weeks of treatment
Secondary outcomes:
measure: Number of Participants Achieving a 15% or Greater Reduction From Baseline to Last On-treatment Urine Albumin to Creatinine Ratio (UACR) Levels.
timeFrame: Baseline (within 1 week prior to first treatment) through 24 weeks of treatment
measure: Change From Baseline to the Last On-treatment Measurement in Albumin Levels Determined From 24-hour Urine Collection.
timeFrame: Baseline (within 1 week prior to first treatment) through 24 weeks of treatment
measure: Change From Baseline to the Last On-treatment Observation in Intact Parathyroid Hormone (iPTH) Levels.
timeFrame: Baseline (screening period) through 24 weeks of treatment
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Site Reference ID/Investigator# 862
state: Arizona
city: Fountain Valley
country: United States
facility: Site Reference ID/Investigator# 864
state: California
city: Yuba City
country: United States
facility: Site Reference ID/Investigator# 7291
state: California
city: Hudson
country: United States
facility: Site Reference ID/Investigator# 853
state: Florida
city: Lauderdale Lakes
country: United States
facility: Site Reference ID/Investigator# 867
state: Florida
city: Pembroke Pines
country: United States
facility: Site Reference ID/Investigator# 857
state: Florida
city: West Palm Beach
country: United States
facility: Site Reference ID/Investigator# 8901
state: Florida
city: Roswell
country: United States
facility: Site Reference ID/Investigator# 7113
state: Georgia
city: Chicago
country: United States
facility: Site Reference ID/Investigator# 2531
state: Illinois
city: Evanston
country: United States
facility: Site Reference ID/Investigator# 3371
state: Illinois
city: Indianapolis
country: United States
facility: Site Reference ID/Investigator# 869
state: Indiana
city: Baton Rouge
country: United States
facility: Site Reference ID/Investigator# 8054
state: Louisiana
city: Rockville
country: United States
facility: Site Reference ID/Investigator# 854
state: Maryland
city: Boston
country: United States
facility: Site Reference ID/Investigator# 6281
state: Massachusetts
city: Brooklyn Center
country: United States
facility: Site Reference ID/Investigator# 859
state: Minnesota
city: Omaha
country: United States
facility: Site Reference ID/Investigator# 7214
state: Nebraska
city: Albany
country: United States
facility: Site Reference ID/Investigator# 8046
state: New York
city: Charlotte
country: United States
facility: Site Reference ID/Investigator# 866
state: North Carolina
city: Greenville
country: United States
facility: Site Reference ID/Investigator# 8039
state: North Carolina
city: Morehead City
country: United States
facility: Site Reference ID/Investigator# 8053
state: North Carolina
city: Winston-Salem
country: United States
facility: Site Reference ID/Investigator# 6626
state: North Carolina
city: Carlisle
country: United States
facility: Site Reference ID/Investigator# 7495
state: Pennsylvania
city: Dallas
country: United States
facility: Site Reference ID/Investigator# 9061
state: Texas
city: Dallas
country: United States
facility: Site Reference ID/Investigator# 8325
state: Texas
city: Dallas
country: United States
facility: Site Reference ID/Investigator# 856
state: Texas
city: San Antonio
country: United States
facility: Site Reference ID/Investigator# 7494
state: Texas
city: San Antonio
country: United States
facility: Site Reference ID/Investigator# 774
state: Texas
city: Duesseldorf
country: Germany
facility: Site Reference ID/Investigator# 6316
city: Hannover
country: Germany
facility: Site Reference ID/Investigator# 5167
city: Ludwigshafen
country: Germany
facility: Site Reference ID/Investigator# 6302
city: Athens
country: Greece
facility: Site Reference ID/Investigator# 6314
city: Ioannina
country: Greece
facility: Site Reference ID/Investigator# 6306
city: Thessaloniki
country: Greece
facility: Site Reference ID/Investigator# 5631
city: Thessaloniki
country: Greece
facility: Site Reference ID/Investigator# 6310
city: Bergamo
country: Italy
facility: Site Reference ID/Investigator# 6312
city: Brescia
country: Italy
facility: Site Reference ID/Investigator# 6303
city: Milan
country: Italy
facility: Site Reference ID/Investigator# 6309
city: Modena
country: Italy
facility: Site Reference ID/Investigator# 6210
city: Groningen
country: Netherlands
facility: Site Reference ID/Investigator# 6207
city: Bydgoszcz
country: Poland
facility: Site Reference ID/Investigator# 6304
city: Katowice
country: Poland
facility: Site Reference ID/Investigator# 5622
city: Szczecin
country: Poland
facility: Site Reference ID/Investigator# 5203
city: Warsaw
country: Poland
facility: Site Reference ID/Investigator# 6315
city: Lisbon
country: Portugal
facility: Site Reference ID/Investigator# 6327
city: Porto
country: Portugal
facility: Site Reference ID/Investigator# 6326
city: Caguas
country: Puerto Rico
facility: Site Reference ID/Investigator# 6916
city: Carolina
country: Puerto Rico
facility: Site Reference ID/Investigator# 5175
city: Las Piedras
country: Puerto Rico
facility: Site Reference ID/Investigator# 6290
city: Ponce
country: Puerto Rico
facility: Site Reference ID/Investigator# 5179
city: Ponce
country: Puerto Rico
facility: Site Reference ID/Investigator# 6293
city: Ponce
country: Puerto Rico
facility: Site Reference ID/Investigator# 5173
city: Ponce
country: Puerto Rico
facility: Site Reference ID/Investigator# 6300
city: Ponce
country: Puerto Rico
facility: Site Reference ID/Investigator# 5168
city: Rio Piedras
country: Puerto Rico
facility: Site Reference ID/Investigator# 7298
city: San Juan
country: Puerto Rico
facility: Site Reference ID/Investigator# 5170
city: San Juan
country: Puerto Rico
facility: Site Reference ID/Investigator# 7509
city: San Juan
country: Puerto Rico
facility: Site Reference ID/Investigator# 6288
city: San Juan
country: Puerto Rico
facility: Site Reference ID/Investigator# 6291
city: Toa Baja
country: Puerto Rico
facility: Site Reference ID/Investigator# 6919
city: Yabucoa
country: Puerto Rico
facility: Site Reference ID/Investigator# 6296
city: Barcelona
country: Spain
facility: Site Reference ID/Investigator# 6569
city: Galdakao
country: Spain
facility: Site Reference ID/Investigator# 10621
city: L'Hospitalet de
country: Spain
facility: Site Reference ID/Investigator# 6330
city: Madrid
country: Spain
facility: Site Reference ID/Investigator# 5111
city: Oviedo
country: Spain
facility: Site Reference ID/Investigator# 5110
city: Santander
country: Spain
facility: Site Reference ID/Investigator# 6329
city: Valencia
country: Spain
facility: Site Reference ID/Investigator# 11281
city: Hsin-Chuang City
country: Taiwan
facility: Site Reference ID/Investigator# 6286
city: Taichung City
country: Taiwan
facility: Site Reference ID/Investigator# 8335
city: Taichung
country: Taiwan
facility: Site Reference ID/Investigator# 7927
city: Taipei City
country: Taiwan
facility: Site Reference ID/Investigator# 6294
city: Taipei
country: Taiwan
facility: Site Reference ID/Investigator# 6285
Study officials:
affiliation: Abbott
name: Dennis Andress, MD
role: STUDY_DIRECTOR
References:
citation: Coyne DW, Andress DL, Amdahl MJ, Ritz E, de Zeeuw D. Effects of paricalcitol on calcium and phosphate metabolism and markers of bone health in patients with diabetic nephropathy: results of the VITAL study. Nephrol Dial Transplant. 2013 Sep;28(9):2260-8. doi: 10.1093/ndt/gft227. Epub 2013 Jun 19.
citation: de Zeeuw D, Agarwal R, Amdahl M, Audhya P, Coyne D, Garimella T, Parving HH, Pritchett Y, Remuzzi G, Ritz E, Andress D. Selective vitamin D receptor activation with paricalcitol for reduction of albuminuria in patients with type 2 diabetes (VITAL study): a randomised controlled trial. Lancet. 2010 Nov 6;376(9752):1543-51. doi: 10.1016/S0140-6736(10)61032-X.