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

NCT00421733 | Completed Phase 2 Results

• 2 other identifiers: M05-7412006-001363-31
• Study Type: interventional
• Target: 281
• Locations: 10 countries
• Sites: 72

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.

Conditions

Diabetic Nephropathy; Chronic Kidney Disease

Keywords

Type 2 Diabetic Nephropathy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• 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

• 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

• Change From Baseline to the Last On-treatment Observation in Intact Parathyroid Hormone (iPTH) Levels.

  Baseline (screening period) through 24 weeks of treatment

Study Arms (3)

Paricalcitol 1 mcg

ACTIVE COMPARATOR

One paricalcitol 1 mcg capsule and one matching placebo capsule per dose

Drug: Zemplar (paricalcitol ) capsules

Paricalcitol 2 mcg

ACTIVE COMPARATOR

Two paricalcitol 1 mcg capsules per dose

Drug: Zemplar (paricalcitol) capsules

Placebo

PLACEBO COMPARATOR

Two placebo capsules per dose

Drug: Placebo

Interventions

Zemplar (paricalcitol) capsules DRUG

Group 3 - paricalcitol 2 mcg capsules once daily (two paricalcitol 1 mcg capsules once daily)

Also known as: ABT-358, paricalcitol, Zemplar

Paricalcitol 2 mcg

Placebo DRUG

Group 1 - Placebo once daily (two placebo capsules once daily)

Placebo

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Abbott: lead

Study Sites (72)

Site Reference ID/Investigator# 862

Phoenix, Arizona, 85012, United States

Location

Site Reference ID/Investigator# 864

Fountain Valley, California, 92708, United States

Location

Site Reference ID/Investigator# 7291

Yuba City, California, 95991, United States

Location

Site Reference ID/Investigator# 853

Hudson, Florida, 34667, United States

Location

Site Reference ID/Investigator# 867

Lauderdale Lakes, Florida, 33313, United States

Location

Site Reference ID/Investigator# 857

Pembroke Pines, Florida, 33028, United States

Location

Site Reference ID/Investigator# 8901

West Palm Beach, Florida, 33401, United States

Location

Site Reference ID/Investigator# 7113

Roswell, Georgia, 30076, United States

Location

Site Reference ID/Investigator# 2531

Chicago, Illinois, 60654, United States

Location

Site Reference ID/Investigator# 3371

Evanston, Illinois, 60201, United States

Location

Site Reference ID/Investigator# 869

Indianapolis, Indiana, 46202, United States

Location

Site Reference ID/Investigator# 8054

Baton Rouge, Louisiana, 70808, United States

Location

Site Reference ID/Investigator# 854

Rockville, Maryland, 20852, United States

Location

Site Reference ID/Investigator# 6281

Boston, Massachusetts, 02215, United States

Location

Site Reference ID/Investigator# 859

Brooklyn Center, Minnesota, 55430, United States

Location

Site Reference ID/Investigator# 7214

Omaha, Nebraska, 68131, United States

Location

Site Reference ID/Investigator# 8046

Albany, New York, 12206, United States

Location

Site Reference ID/Investigator# 866

Charlotte, North Carolina, 28208, United States

Location

Site Reference ID/Investigator# 8039

Greenville, North Carolina, 27834, United States

Location

Site Reference ID/Investigator# 8053

Morehead City, North Carolina, 28557, United States

Location

Site Reference ID/Investigator# 6626

Winston-Salem, North Carolina, 27103, United States

Location

Site Reference ID/Investigator# 7495

Carlisle, Pennsylvania, 17015, United States

Location

Site Reference ID/Investigator# 9061

Dallas, Texas, 75230, United States

Location

Site Reference ID/Investigator# 8325

Dallas, Texas, 75231, United States

Location

Site Reference ID/Investigator# 856

Dallas, Texas, 75390, United States

Location

Site Reference ID/Investigator# 7494

San Antonio, Texas, 78229, United States

Location

Site Reference ID/Investigator# 774

San Antonio, Texas, 78229, United States

Location

Site Reference ID/Investigator# 6316

Düsseldorf, 40210, Germany

Location

Site Reference ID/Investigator# 5167

Hanover, 30625, Germany

Location

Site Reference ID/Investigator# 6302

Ludwigshafen, 67059, Germany

Location

Site Reference ID/Investigator# 6314

Athens, 18454, Greece

Location

Site Reference ID/Investigator# 6306

Ioannina, 45500, Greece

Location

Site Reference ID/Investigator# 5631

Thessaloniki, 54636, Greece

Location

Site Reference ID/Investigator# 6310

Thessaloniki, 54642, Greece

Location

Site Reference ID/Investigator# 6312

Bergamo, 24128, Italy

Location

Site Reference ID/Investigator# 6303

Brescia, 25123, Italy

Location

Site Reference ID/Investigator# 6309

Milan, 20142, Italy

Location

Site Reference ID/Investigator# 6210

Modena, 41100, Italy

Location

Site Reference ID/Investigator# 6207

Groningen, 9713 GZ, Netherlands

Location

Site Reference ID/Investigator# 6304

Bydgoszcz, 85-094, Poland

Location

Site Reference ID/Investigator# 5622

Katowice, 40027, Poland

Location

Site Reference ID/Investigator# 5203

Szczecin, 70-111, Poland

Location

Site Reference ID/Investigator# 6315

Warsaw, 00909, Poland

Location

Site Reference ID/Investigator# 6327

Lisbon, 1069-166, Portugal

Location

Site Reference ID/Investigator# 6326

Porto, 4202-451, Portugal

Location

Site Reference ID/Investigator# 6916

Caguas, 00725, Puerto Rico

Location

Site Reference ID/Investigator# 5175

Carolina, 00983, Puerto Rico

Location

Site Reference ID/Investigator# 6290

Las Piedras, 00771, Puerto Rico

Location

Site Reference ID/Investigator# 5179

Ponce, 00716, Puerto Rico

Location

Site Reference ID/Investigator# 6293

Ponce, 00716, Puerto Rico

Location

Site Reference ID/Investigator# 5173

Ponce, 00717-0634, Puerto Rico

Location

Site Reference ID/Investigator# 6300

Ponce, 00717-1322, Puerto Rico

Location

Site Reference ID/Investigator# 5168

Ponce, 00717-2075, Puerto Rico

Location

Site Reference ID/Investigator# 7298

Rio Piedras, 00935, Puerto Rico

Location

Site Reference ID/Investigator# 5170

San Juan, 00909, Puerto Rico

Location

Site Reference ID/Investigator# 7509

San Juan, 00918, Puerto Rico

Location

Site Reference ID/Investigator# 6288

San Juan, 00921-3201, Puerto Rico

Location

Site Reference ID/Investigator# 6291

San Juan, 00936-5067, Puerto Rico

Location

Site Reference ID/Investigator# 6919

Toa Baja, 00949, Puerto Rico

Location

Site Reference ID/Investigator# 6296

Yabucoa, 00767, Puerto Rico

Location

Site Reference ID/Investigator# 6569

Barcelona, 08036, Spain

Location

Site Reference ID/Investigator# 10621

Galdakao, 48960, Spain

Location

Site Reference ID/Investigator# 6330

L'Hospitalet de, 08907, Spain

Location

Site Reference ID/Investigator# 5111

Madrid, 28041, Spain

Location

Site Reference ID/Investigator# 5110

Oviedo, 33006, Spain

Location

Site Reference ID/Investigator# 6329

Santander, 39008, Spain

Location

Site Reference ID/Investigator# 11281

Valencia, 46017, Spain

Location

Site Reference ID/Investigator# 8335

Taichung, 40764, Taiwan

Location

Site Reference ID/Investigator# 7927

Taichung, 433, Taiwan

Location

Site Reference ID/Investigator# 6294

Taipei, 10449, Taiwan

Location

Site Reference ID/Investigator# 6285

Taipei, Taiwan

Location

Site Reference ID/Investigator# 6286

Xinzhuang, Taiwan

Location

Related Publications (2)

• 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.

  PMID: 23787544 DERIVED

• 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.

  PMID: 21055801 DERIVED

MeSH Terms

Conditions

Diabetic Nephropathies; Renal Insufficiency, Chronic

Interventions

paricalcitol; Capsules

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases; Renal Insufficiency; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations

Results Point of Contact

• Title: Global Medical Services
• Organization: Abbott

800-633-9110

Study Officials

• Dennis Andress, MD

  Abbott

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 10, 2007
• First Posted: January 12, 2007
• Study Start: December 1, 2006
• Primary Completion: June 1, 2009
• Study Completion: June 1, 2009
• Last Updated: January 20, 2012
• Results First Posted: September 14, 2010

Record last verified: 2012-01

Locations

GR (4); IT (4); PT (2); TW (5); US (27); PL (4); DE (3); PR (15); NL (1); ES (7)