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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

October 17, 2011
January 22, 2016
November 2011
January 2013   (final data collection date for primary outcome measure)
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.
Incidence of clinically significant hypocalcemia, defined as albumin-adjusted Ca < 7.0mg/dL or symptomatic hypocalcemia [ Time Frame: 113 days ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01464931 on ClinicalTrials.gov Archive Site
  • 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 ]
  • Incidence and severity of hypocalcemia, hypomagnesemia and hypophosphatemia as determined by CTCAE v.4.0 criteria [ Time Frame: 113 days ] [ Designated as safety issue: Yes ]
  • Laboratory values of albumin-adjusted calcium, magnesium, and phosphorus and their changes compared to baseline [ Time Frame: 113 days ] [ Designated as safety issue: Yes ]
  • Adverse events including clinically significant changes in vital signs, physical examinations, clinical laboratory tests, ECGs; [ Time Frame: 113 days ] [ Designated as safety issue: Yes ]
  • Serum denosumab and C-telopeptide (CTx) concentrations [ Time Frame: 113 days ] [ Designated as safety issue: No ]
  • Incidence of seroreactivity (or antibody positivity) [ Time Frame: 113 days ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
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
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
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
Not Provided
Interventional
Phase 1
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Renal Impairment
Drug: Denosumab
Adminstered by subcutaneous injection
Other Names:
  • XGEVA
  • AMG 162
Experimental: Denosumab
Participants received two 120 mg doses of denosumab administered subcutaneously on Day 1 and Day 29.
Intervention: Drug: Denosumab
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
32
March 2013
January 2013   (final data collection date for primary outcome measure)

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
Both
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01464931
20101361
No
Not Provided
Not Provided
Amgen
Amgen
Not Provided
Study Director: MD Amgen
Amgen
January 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP