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

Renal Impairment Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01464931
• Other study ID #: 20101361
• Status: Completed
• Phase: Phase 1
• First received: October 17, 2011
• Last updated: January 22, 2016
• Start date: November 2011
• Est. completion date: March 2013

Study information

• Verified date: January 2016
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: March 2013
• Est. primary completion date: January 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Kidney Diseases
• Renal Impairment
• Renal Insufficiency
• Renal Insufficiency, Chronic

Intervention

Drug:
• Denosumab
Adminstered by subcutaneous injection

Locations

Country	Name	City	State
United States	Research Site	Denver	Colorado
United States	Research Site	Detroit	Michigan
United States	Research Site	Meridian	Idaho
United States	Research Site	Orangeburg	South Carolina
United States	Research Site	Pembroke Pines	Florida
United States	Research Site	San Antonio	Texas
United States	Research Site	Tempe	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Clinically Significant Hypocalcemia	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.	113 days	Yes
Secondary	Number of Participants With Hypocalcemia Determined by CTCAE v.4.0 Criteria	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.	113 days	Yes
Secondary	Number of Participants With Hypophosphatemia Determined by CTCAE v.4.0 Criteria	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.	113 days	Yes
Secondary	Number of Participants With Hypomagnesemia Determined by CTCAE v.4.0 Criteria	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.	113 days	Yes
Secondary	Percent Change From Baseline in Albumin-adjusted Serum Calcium Over Time		Baseline and Days 2, 3, 6, 8, 11, 15, 22, 29, 30, 31, 34, 36, 39, 43, 57, 71, 85, and 113	Yes
Secondary	Percent Change From Baseline in Serum Phosphorus Over Time		Baseline and Days 2, 3, 6, 8, 11, 15, 22, 29, 30, 31, 34, 36, 39, 43, 57, 71, 85, and 113	Yes
Secondary	Percent Change From Baseline in Serum Magnesium Over Time		Baseline and Days 2, 3, 6, 8, 11, 15, 22, 29, 30, 31, 34, 36, 39, 43, 57, 71, 85, and 113	Yes
Secondary	Number of Participants With Adverse Events	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.	113 days	Yes
Secondary	Maximum Observed Serum Denosumab Concentration (Cmax)	Serum concentrations of denosumab were measured by an enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) was 20 ng/mL.	Days 1 and 29 (predose), and on Days 8, 15, 36, 43, 57, 71, 85, and 113	No
Secondary	Time to Maximum Observed Serum Denosumab Concentration (Tmax)	Serum concentrations of denosumab were measured by an enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) was 20 ng/mL.	Days 1 and 29 (predose), and on Days 8, 15, 36, 43, 57, 71, 85, and 113	No
Secondary	Area Under the Serum Concentration-time Curve From Time 0 to 4 Weeks (AUC0-4wks) After Dose 1	Estimated using the linear trapezoidal method.	Days 1, 8, 15, and 29 (predose)	No
Secondary	Area Under the Serum Concentration-time Curve From Time 0 to 12 Weeks (AUC0-12wks) After Dose 2	Estimated using the linear trapezoidal method.	Days 29 (predose), 36, 43, 57, 71, and 85	No
Secondary	Percent Change From Baseline in Serum C-Telopeptide Over Time		Baseline and Days 1 and 29 (predose), and on Days 8, 15, 36, 43, 57, 71, 85, and 113	No
Secondary	Number of Participants Who Developed Anti-denosumab Antibodies		From Day 1 (predose) to Day 113	No

External Links

•   AmgenTrials clinical trials website