Bone Biopsy Study For Dialysis Patients With Secondary Hyperparathyroidism of End Stage Renal Disease (BONAFIDE)

Bone Histomorphometry Assessment For Dialysis Patients With Secondary Hyperparathyroidism of End Stage Renal Disease

The purpose of this study is to evaluate the effects of cinacalcet on markers of bone turnover in patients with kidney disease who are receiving dialysis.

Study Overview

• Status: Completed
• Conditions: Secondary Hyperparathyroidism
• Intervention / Treatment: Drug: Sensipar (Cinacalcet HCl)

Detailed Description

Secondary hyperparathyroidism (HPT) is common in people with end stage renal disease (kidney disease). Patients with secondary HPT often have enlarged parathyroid glands in the neck and as a result often have elevated parathyroid hormone (PTH) levels . Patients with secondary HPT may have bone disease (osteodystrophy). Cinacalcet has been used to decrease PTH levels in patients with secondary HPT. Patients with secondary HPT may have bone disease (osteodystrophy). This bone disease may cause bone pain, fractures, and poor formation of red blood cells. The purpose of this study is to evaluate effects of cinacalcet on markers of bone turnover in patients with kidney disease who are receiving dialysis.

• Study Type: Interventional
• Enrollment (Actual): 110
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Antwerpen, Belgium, 2060
    • Research Site
  • Antwerpen, Belgium, 2020
    • Research Site
  • Bruxelles, Belgium, 1070
    • Research Site
  • Leuven, Belgium, 3000
    • Research Site
  • Liege, Belgium, 4000
    • Research Site
• Czech Republic
  • Hradec Kralove, Czech Republic, 500 05
    • Research Site
  • Praha 6, Czech Republic, 169 00
    • Research Site
• Hungary
  • Budapest, Hungary, 1083
    • Research Site
  • Debrecen, Hungary, 4012
    • Research Site
  • Gyor, Hungary, 9023
    • Research Site
  • Miskolc, Hungary, 3526
    • Research Site
  • Nyiregyhaza, Hungary, 4400
    • Research Site
• Italy
  • Avellino, Italy, 83100
    • Research Site
  • Cremona, Italy, 26100
    • Research Site
  • Genova, Italy, 16132
    • Research Site
  • Milano, Italy, 20162
    • Research Site
  • Ortona CH, Italy, 66026
    • Research Site
  • Ostia RM, Italy, 00122
    • Research Site
  • Roma, Italy, 00149
    • Research Site
  • Roma, Italy, 00184
    • Research Site
  • Roma (RM), Italy, 00133
    • Research Site
• Macedonia, The Former Yugoslav Republic of
  • Skopje, Macedonia, The Former Yugoslav Republic of, 1000
    • Research Site
• Poland
  • Krakow, Poland, 31-501
    • Research Site
  • Lodz, Poland, 90-153
    • Research Site
  • Wroclaw, Poland, 50-556
    • Research Site
• Portugal
  • Almada, Portugal, 2800-455
    • Research Site
  • Estoril, Portugal, 2765-294
    • Research Site
  • Guimarães, Portugal, 4810-273
    • Research Site
  • Porto, Portugal, 4200-072
    • Research Site
  • Vila Franca de Xira, Portugal, 2600-076
    • Research Site
  • PR
    • Porto, PR, Portugal, 4250-499
      • Research Site
• Spain
  • Madrid, Spain, 28046
    • Research Site
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Research Site
  • Cataluña
    • Barcelona, Cataluña, Spain, 08003
      • Research Site
    • Barcelona, Cataluña, Spain, 08036
      • Research Site
  • Madrid
    • Alcorcón, Madrid, Spain, 28922
      • Research Site
• Switzerland
  • Zurich, Switzerland, 8091
    • Research Site
• Turkey
  • Izmir, Turkey, 35360
    • Research Site
• United Kingdom
  • Manchester, United Kingdom, M13 9WL
    • Research Site
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85012
      • Research Site
  • California
    • Los Angeles, California, United States, 90095
      • Research Site
  • Colorado
    • Denver, Colorado, United States, 80220
      • Research Site
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Research Site
  • Florida
    • Fort Lauderdale, Florida, United States, 33334
      • Research Site
  • Illinois
    • Evanston, Illinois, United States, 60201
      • Research Site
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Research Site
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Research Site
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Research Site
  • New Jersey
    • Teaneck, New Jersey, United States, 07666
      • Research Site
  • New York
    • Bronx, New York, United States, 10467
      • Research Site
    • Flushing, New York, United States, 11355
      • Research Site
    • Great Neck, New York, United States, 11021
      • Research Site
    • New York, New York, United States, 10032
      • Research Site
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18103
      • Research Site
  • Texas
    • Houston, Texas, United States, 77076
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria: Subjects will be eligible for the study if they meet all of the following criteria:

• One Intact Parathyroid Hormone (iPTH) determination obtained from the central laboratory must be >/= 300 pg/mL.
• One serum calcium determination obtained from the central laboratory must be >/= 8.4 mg/dL (2.1 mmol/L).
• One Bone Alkaline Phosphatase (BALP) determination obtained from the central laboratory must be >/= 20.9 ng/mL.
• Positive histologic confirmation of high bone turnover disease as assessed by the central bone histology center.
• Treated with dialysis >/= 1 month before the date of informed consent.

Exclusion Criteria: Subjects will be ineligible for the study if they:

• Have an unstable medical condition in the judgment of the investigator.
• Are pregnant or nursing women.
• Had a parathyroidectomy in the 3 months before the date of informed consent.
• For subjects prescribed vitamin D, have received vitamin D therapy for less than 30 days before day 1 or required a change in vitamin D brand or dose level within 30 days before day 1.
• Ever received therapy with Sensipar®/Mimpara®

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Cinacalcet; All subjects were enrolled into the single arm to receive Cinacalcet. There was no comparator arm.

Drug: Sensipar (Cinacalcet HCl); All enrolled subjects receive study medication at a starting dose of 30 mg cinacalcet once daily beginning on day 1. Possible sequential doses are 30 mg, 60mg, 90mg, 120mg, 180 mg taken once daily. During the study, dose adjustment (dose increase/decrease/withholding) is based upon iPTH, serum calcium, and subject safety information. Subjects swallowed tablets whole without biting or chewing. Subjects were dispensed investigational product every 4 weeks starting from Day 1 through to Week 48.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change From Baseline to End of Study in Bone Formation Rate (BFR)	Baseline to week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Serum Calcium During the Efficacy Assessment Phase (EAP)		Baseline to weeks 40-52
Percent Change From Baseline in Serum Phosphorus During the Efficacy Assessment Phase (EAP)		Baseline to weeks 40-52
Percent Change From Baseline in Ca x P During the Efficacy Assessment Phase (EAP)		Baseline to weeks 40-52
Percent Change From Baseline in Bone Specific Alkaline Phosphatase (BALP) at Week 52		Baseline to week 52
Percent Change From Baseline in N - Telopeptide (NTx) at Week 52		Baseline to week 52
Percent Change From Baseline in Parathyroid Hormone (PTH) During the Efficacy Assessment Phase (EAP)		Baseline to weeks 40-52
Change From Baseline to End of Study in Osteoblast Perimeter (Osteoblast Perimeter/Osteoid Perimeter)	Osteoblast Perimeter was calculated as "Osteoblast Perimeter/Osteoid Perimeter * 100"	Baseline to week 52
Change From Baseline to End of Study in Osteoclast Perimeter (Osteoclast Perimeter/Eroded Perimeter)	Osteoclast Perimeter was calculated as "Osteoclast Perimeter/Eroded Perimeter * 100"	Baseline to week 52
Change in Categorization From Baseline to End of Study in Fibrosis Area/Tissue Area	Categorisation at each timepoint was based on fibrosis area as a percentage of tissue area (Fibrosis Area/Tissue Area * 100)	Baseline to week 52
Change From Baseline to End of Study in Eroded Perimeter/Bone Perimeter	Eroded Perimeter/Bone Perimeter was calculated as "Eroded Perimeter/Bone Perimeter * 100"	Baseline to week 52
Percent Change From Baseline in Osteocalcin (OC) at Week 52		Baseline to week 52
Percent Change From Baseline in Tartrate Resistant Acid Phosphatase(TRAP) at Week 52		Baseline to week 52

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

General Publications

• TBD.BONAFIDE Baseline/Primary Results.Journal-004521;
• Behets GJ, Spasovski G, Sterling LR, Goodman WG, Spiegel DM, De Broe ME, D'Haese PC. Bone histomorphometry before and after long-term treatment with cinacalcet in dialysis patients with secondary hyperparathyroidism. Kidney Int. 2015 Apr;87(4):846-56. doi: 10.1038/ki.2014.349. Epub 2014 Oct 22.

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start: May 1, 2006
• Primary Completion (Actual): May 1, 2011
• Study Completion (Actual): May 1, 2011

Study Registration Dates

• First Submitted: December 2, 2005
• First Submitted That Met QC Criteria: December 2, 2005
• First Posted (Estimate): December 6, 2005

Study Record Updates

• Last Update Posted (Estimate): July 21, 2014
• Last Update Submitted That Met QC Criteria: June 24, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Keywords: Cinacalcet HCl, Cinacalcet, Amgen (AMG) 073, Sensipar, Mimpara, Calcimimetic
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Kidney Diseases; Urologic Diseases; Endocrine System Diseases; Renal Insufficiency; Parathyroid Diseases; Neoplastic Processes; Renal Insufficiency, Chronic; Hyperparathyroidism; Neoplasm Metastasis; Kidney Failure, Chronic; Hyperparathyroidism, Secondary; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Calcium-Regulating Hormones and Agents; Calcimimetic Agents; Cinacalcet
• Other Study ID Numbers: 20050104; BONAFIDE Study (Other Identifier: Amgen); IND #56,010 (Other Identifier: Food and Drug Administration)