Effects of Denosumab on the Pharmacokinetics of Etanercept

Study Overview
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Brief Summary
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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).

Official Title
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The Effects of Denosumab on the Pharmacokinetics of Etanercept in Postmenopausal Women With Low Bone Mineral Density and Rheumatoid Arthritis

Conditions
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Postmenopausal, Osteopenia, Rheumatoid Arthritis, Osteoporosis

Intervention / Treatment
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* Drug: Etanercept
* Drug: Denosumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Etanercept + Denosumab<br>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. | Drug: Etanercept<br>* Administered by subcutaneous injection once a week<br>* Other names: Enbrel®;Drug: Denosumab<br>* Administered by subcutaneous injection<br>* Other names: Prolia®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | Day 1 and day 22; at each time point samples were taken predose and 2, 3, 4, 5, 6 and 8 days postdose. | 
| Maximum Observed Serum Concentration (Cmax) of Etanercept |  | 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 Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Maximum Serum Concentration (Tmax) of Etanercept |  | Day 1 and day 22; at each time point samples were taken predose and 2, 3, 4, 5, 6 and 8 days postdose. | 
| Serum Denosumab Concentration |  | Prior to etanercept and denosumab dose administrations, as applicable, on days 8, 22, and 29 | 
| Percent Change From Baseline in Serum C-telopeptide (sCTx) Concentrations |  | Baseline (Day 8) and Days 22, 29, 85, and 176 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Amgen, Phase 1, Postmenopausal, Osteopenia, Rheumatoid, Bone Mineral Density, Arthritis, Pharmacokinetics, Osteoporosis