Multiple Dose Study to Evaluate the Safety of Multiple Doses of Denosumab 120 mg in Adults With Severe Chronic Kidney Disease (CKD) and CKD on Dialysis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT01464931
First received: October 17, 2011
Last updated: January 22, 2016
Last verified: January 2016
  Purpose
The primary objective was to evaluate the incidence of clinically significant hypocalcemia following multiple 120 mg subcutaneous doses of denosumab in patients with severe chronic kidney disease (CKD) and CKD on dialysis

Condition Intervention Phase
Renal Impairment
Drug: Denosumab
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label Study to Evaluate the Safety of Multiple Doses of Denosumab 120 mg Administered Subcutaneously in Subjects With Severe Chronic Kidney Disease (CKD) and CKD on Dialysis

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • Number of Participants With Clinically Significant Hypocalcemia [ Time Frame: 113 days ] [ Designated as safety issue: Yes ]
    Clinically significant hypocalcemia is defined as albumin-adjusted calcium < 7.0 mg/dL or symptomatic hypocalcemia. Symptomatic hypocalcemiais is defined as both a clinical adverse event of hypocalcemia and a concomitant symptom of hypocalcemia (e.g., hypoesthesia, paresthesia, muscle cramps, seizure, prolonged QT interval) that occurred along with the hypocalcemia event or decreased serum calcium levels.


Secondary Outcome Measures:
  • Number of Participants With Hypocalcemia Determined by CTCAE v.4.0 Criteria [ Time Frame: 113 days ] [ Designated as safety issue: Yes ]
    The severity of hypocalcemia (a low concentration of calcium, corrected for albumin, in the blood) was graded according to the common terminology criteria for adverse events (CTCAE) v.4.0 criteria: Grade 1: albumin-adjusted serum calcium < lower limit of normal (LLN; 9.2 mg/dL) to 8.0 mg/dL; Grade 2: albumin-adjusted serum calcium < 8.0 to 7.0 mg/dL; Grade 3: albumin-adjusted serum calcium < 7.0 to 6.0 mg/dL; Grade 4: albumin-adjusted serum calcium < 6.0 mg/dL.

  • Number of Participants With Hypophosphatemia Determined by CTCAE v.4.0 Criteria [ Time Frame: 113 days ] [ Designated as safety issue: Yes ]
    The severity of hypophosphatemia (a low concentration of phosphates in the blood) was graded according to the common terminology criteria for adverse events (CTCAE) v.4.0 criteria: Grade 1: < LLN (3 mg/dL) - 2.5 mg/dL; Grade 2: < 2.5 - 2.0 mg/dL; Grade 3: < 2.0 - 1.0 mg/dL; Grade 4: < 1.0 mg/dL.

  • Number of Participants With Hypomagnesemia Determined by CTCAE v.4.0 Criteria [ Time Frame: 113 days ] [ Designated as safety issue: Yes ]
    The severity of hypomagnesemia (a low concentration of magnesium in the blood) was graded according to the common terminology criteria for adverse events (CTCAE) v.4.0 criteria: Grade 1: < LLN (1.5 mg/dL) - 1.2 mg/dL; Grade 2: < 1.2 - 0.9 mg/dL; Grade 3: < 0.9 - 0.7 mg/dL; Grade 4: < 0.7 mg/dL.

  • Percent Change From Baseline in Albumin-adjusted Serum Calcium Over Time [ Time Frame: Baseline and Days 2, 3, 6, 8, 11, 15, 22, 29, 30, 31, 34, 36, 39, 43, 57, 71, 85, and 113 ] [ Designated as safety issue: Yes ]
  • Percent Change From Baseline in Serum Phosphorus Over Time [ Time Frame: Baseline and Days 2, 3, 6, 8, 11, 15, 22, 29, 30, 31, 34, 36, 39, 43, 57, 71, 85, and 113 ] [ Designated as safety issue: Yes ]
  • Percent Change From Baseline in Serum Magnesium Over Time [ Time Frame: Baseline and Days 2, 3, 6, 8, 11, 15, 22, 29, 30, 31, 34, 36, 39, 43, 57, 71, 85, and 113 ] [ Designated as safety issue: Yes ]
  • Number of Participants With Adverse Events [ Time Frame: 113 days ] [ Designated as safety issue: Yes ]
    The severity of each adverse event (AE) was graded using the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. The investigator assessed whether AEs were possibly related to study drug by answering the question: "Is there a reasonable possibility that the event may have been caused by the investigational product?" Abnormal laboratory findings without clinical significance (based on the investigator's judgment) were not recorded as AEs, however, laboratory value changes that required treatment or adjustment in current therapy were considered AEs. A serious adverse event is defined as an adverse event that meets at least 1 of the following serious criteria: • fatal, • life-threatening (places the participant at immediate risk of death), • requires in-patient hospitalization or prolongation of existing hospitalization, • results in persistent or significant disability/incapacity, • congenital anomaly/birth defect, and/or • other medically important serious event.

  • Maximum Observed Serum Denosumab Concentration (Cmax) [ Time Frame: Days 1 and 29 (predose), and on Days 8, 15, 36, 43, 57, 71, 85, and 113 ] [ Designated as safety issue: No ]
    Serum concentrations of denosumab were measured by an enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) was 20 ng/mL.

  • Time to Maximum Observed Serum Denosumab Concentration (Tmax) [ Time Frame: Days 1 and 29 (predose), and on Days 8, 15, 36, 43, 57, 71, 85, and 113 ] [ Designated as safety issue: No ]
    Serum concentrations of denosumab were measured by an enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) was 20 ng/mL.

  • Area Under the Serum Concentration-time Curve From Time 0 to 4 Weeks (AUC0-4wks) After Dose 1 [ Time Frame: Days 1, 8, 15, and 29 (predose) ] [ Designated as safety issue: No ]
    Estimated using the linear trapezoidal method.

  • Area Under the Serum Concentration-time Curve From Time 0 to 12 Weeks (AUC0-12wks) After Dose 2 [ Time Frame: Days 29 (predose), 36, 43, 57, 71, and 85 ] [ Designated as safety issue: No ]
    Estimated using the linear trapezoidal method.

  • Percent Change From Baseline in Serum C-Telopeptide Over Time [ Time Frame: Baseline and Days 1 and 29 (predose), and on Days 8, 15, 36, 43, 57, 71, 85, and 113 ] [ Designated as safety issue: No ]
  • Number of Participants Who Developed Anti-denosumab Antibodies [ Time Frame: From Day 1 (predose) to Day 113 ] [ Designated as safety issue: No ]

Enrollment: 32
Study Start Date: November 2011
Study Completion Date: March 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Denosumab
Participants received two 120 mg doses of denosumab administered subcutaneously on Day 1 and Day 29.
Drug: Denosumab
Adminstered by subcutaneous injection
Other Names:
  • XGEVA
  • AMG 162

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects at least 18 years old with severe CKD (defined as creatinine clearance < 30 mL/min at both screening assessments) and CKD requiring hemodialysis
  • Additional inclusion criteria apply

Exclusion Criteria:

  • Subjects must have calcium, phosphate, and magnesium levels appropriate for their condition and must not have other uncontrolled co-morbidities.
  • Additional exclusion criteria apply
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01464931

Locations
United States, Arizona
Research Site
Tempe, Arizona, United States, 85284
United States, Colorado
Research Site
Denver, Colorado, United States, 80230
United States, Florida
Research Site
Pembroke Pines, Florida, United States, 33028
United States, Idaho
Research Site
Meridian, Idaho, United States, 83642
United States, Michigan
Research Site
Detroit, Michigan, United States, 48236
United States, South Carolina
Research Site
Orangeburg, South Carolina, United States, 29118
United States, Texas
Research Site
San Antonio, Texas, United States, 78215
Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT01464931     History of Changes
Other Study ID Numbers: 20101361 
Study First Received: October 17, 2011
Results First Received: December 14, 2015
Last Updated: January 22, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Kidney Diseases
Renal Insufficiency, Chronic
Renal Insufficiency
Urologic Diseases
Denosumab
Bone Density Conservation Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 26, 2016