Effects of Denosumab on the Pharmacokinetics of Etanercept
Primary Purpose
Postmenopausal, Osteopenia, Rheumatoid Arthritis
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Etanercept
Denosumab
Sponsored by
About this trial
This is an interventional treatment trial for Postmenopausal focused on measuring Amgen, Phase 1, Postmenopausal, Osteopenia, Rheumatoid, Bone Mineral Density, Arthritis, Pharmacokinetics, Osteoporosis
Eligibility Criteria
Inclusion Criteria:
- Postmenopausal women (postmenopausal is defined as no vaginal bleeding or spotting for at least 12 months)
- Low bone mineral density (BMD) as determined by screening BMD T-scores of the lumbar spine (L1 to L4), or total evaluable vertebrae (if fewer than L1 to L4), or total hip ≤ -1.0
- Receiving a 50 mg dose of etanercept once weekly ≥ 6 months prior to screening and expected to continue etanercept treatment at this dose and frequency through end of study (EOS)
- If currently taking methotrexate (MTX), receiving a stable dose (7.5 to 20 mg/week) of MTX ≥ 8 weeks prior to screening
- Willing and able to take ≥ 1,000 mg elemental calcium and ≥ 400 IU vitamin D daily upon enrollment
Exclusion Criteria:
- Type 1 diabetes; OR poorly controlled Type 2 diabetes (hemoglobin A1c (HbA1c) > 8.0% at screening; HbA1c ≤ 8.0% within 6 months of screening is acceptable if supporting laboratory documentation is available)
- History of heart failure, coronary artery bypass graft, or cardiac arrhythmia; OR history of acute coronary syndrome
- Comorbid autoimmune disease, demyelinating disease, or hematologic abnormalities
- History of joint replacement in hand and/or wrist; OR history of fused joint in hand and/or wrist
- Prior history or current evidence of osteonecrosis/osteomyelitis of the jaw; OR active dental or jaw condition that requires oral surgery, or non-healed dental/oral surgery; OR planned invasive dental procedure(s) during the course of the study
- Previous exposure to denosumab
Sites / Locations
- Research Site
- Research Site
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Etanercept + Denosumab
Arm Description
Participants received etanercept 50 mg subcutaneously once weekly for 25 weeks. On study day 8, participants were administered a single 60 mg subcutaneous injection of denosumab.
Outcomes
Primary Outcome Measures
Area Under the Serum Concentration-time Curve From 0 to 168 Hours (AUC0-168) for Etanercept
The AUC0-168 of etanercept was measured when administered alone (assessed from day 1) and after administration with denosumab (assessed from day 22, 14 days after denosumab dosing, close to the time of the maximum observed denosumab serum concentration and corresponding to a time approximately 1 week after maximal pharmacodynamic (PD) effects of denosumab are attained).
Maximum Observed Serum Concentration (Cmax) of Etanercept
Secondary Outcome Measures
Time to Maximum Serum Concentration (Tmax) of Etanercept
Serum Denosumab Concentration
Percent Change From Baseline in Serum C-telopeptide (sCTx) Concentrations
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01294397
Brief Title
Effects of Denosumab on the Pharmacokinetics of Etanercept
Official Title
The Effects of Denosumab on the Pharmacokinetics of Etanercept in Postmenopausal Women With Low Bone Mineral Density and Rheumatoid Arthritis
Study Type
Interventional
2. Study Status
Record Verification Date
April 2017
Overall Recruitment Status
Terminated
Why Stopped
Lack of enrollment.
Study Start Date
March 2011 (undefined)
Primary Completion Date
January 2016 (Actual)
Study Completion Date
January 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amgen
4. Oversight
5. Study Description
Brief Summary
The primary objective of the study was to characterize the effects of a single dose of denosumab on the pharmacokinetics (PK) of etanercept in postmenopausal women with low bone mineral density (BMD) and rheumatoid arthritis based on area under the serum concentration-time curve (AUC) and maximum observed serum concentration (Cmax).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Postmenopausal, Osteopenia, Rheumatoid Arthritis, Osteoporosis
Keywords
Amgen, Phase 1, Postmenopausal, Osteopenia, Rheumatoid, Bone Mineral Density, Arthritis, Pharmacokinetics, Osteoporosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
19 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Etanercept + Denosumab
Arm Type
Experimental
Arm Description
Participants received etanercept 50 mg subcutaneously once weekly for 25 weeks. On study day 8, participants were administered a single 60 mg subcutaneous injection of denosumab.
Intervention Type
Drug
Intervention Name(s)
Etanercept
Other Intervention Name(s)
Enbrel®
Intervention Description
Administered by subcutaneous injection once a week
Intervention Type
Drug
Intervention Name(s)
Denosumab
Other Intervention Name(s)
Prolia®
Intervention Description
Administered by subcutaneous injection
Primary Outcome Measure Information:
Title
Area Under the Serum Concentration-time Curve From 0 to 168 Hours (AUC0-168) for Etanercept
Description
The AUC0-168 of etanercept was measured when administered alone (assessed from day 1) and after administration with denosumab (assessed from day 22, 14 days after denosumab dosing, close to the time of the maximum observed denosumab serum concentration and corresponding to a time approximately 1 week after maximal pharmacodynamic (PD) effects of denosumab are attained).
Time Frame
Day 1 and day 22; at each time point samples were taken predose and 2, 3, 4, 5, 6 and 8 days postdose.
Title
Maximum Observed Serum Concentration (Cmax) of Etanercept
Time Frame
Day 1 and day 22; at each time point samples were taken predose and 2, 3, 4, 5, 6 and 8 days postdose.
Secondary Outcome Measure Information:
Title
Time to Maximum Serum Concentration (Tmax) of Etanercept
Time Frame
Day 1 and day 22; at each time point samples were taken predose and 2, 3, 4, 5, 6 and 8 days postdose.
Title
Serum Denosumab Concentration
Time Frame
Prior to etanercept and denosumab dose administrations, as applicable, on days 8, 22, and 29
Title
Percent Change From Baseline in Serum C-telopeptide (sCTx) Concentrations
Time Frame
Baseline (Day 8) and Days 22, 29, 85, and 176
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
45 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Postmenopausal women (postmenopausal is defined as no vaginal bleeding or spotting for at least 12 months)
Low bone mineral density (BMD) as determined by screening BMD T-scores of the lumbar spine (L1 to L4), or total evaluable vertebrae (if fewer than L1 to L4), or total hip ≤ -1.0
Receiving a 50 mg dose of etanercept once weekly ≥ 6 months prior to screening and expected to continue etanercept treatment at this dose and frequency through end of study (EOS)
If currently taking methotrexate (MTX), receiving a stable dose (7.5 to 20 mg/week) of MTX ≥ 8 weeks prior to screening
Willing and able to take ≥ 1,000 mg elemental calcium and ≥ 400 IU vitamin D daily upon enrollment
Exclusion Criteria:
Type 1 diabetes; OR poorly controlled Type 2 diabetes (hemoglobin A1c (HbA1c) > 8.0% at screening; HbA1c ≤ 8.0% within 6 months of screening is acceptable if supporting laboratory documentation is available)
History of heart failure, coronary artery bypass graft, or cardiac arrhythmia; OR history of acute coronary syndrome
Comorbid autoimmune disease, demyelinating disease, or hematologic abnormalities
History of joint replacement in hand and/or wrist; OR history of fused joint in hand and/or wrist
Prior history or current evidence of osteonecrosis/osteomyelitis of the jaw; OR active dental or jaw condition that requires oral surgery, or non-healed dental/oral surgery; OR planned invasive dental procedure(s) during the course of the study
Previous exposure to denosumab
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MD
Organizational Affiliation
Amgen
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Duncansville
State/Province
Pennsylvania
ZIP/Postal Code
16635
Country
United States
Facility Name
Research Site
City
Dallas
State/Province
Texas
ZIP/Postal Code
75231
Country
United States
12. IPD Sharing Statement
Links:
URL
http://www.amgentrials.com
Description
AmgenTrials clinical trials website
Learn more about this trial
Effects of Denosumab on the Pharmacokinetics of Etanercept
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