Effects of Denosumab on the Pharmacokinetics of Etanercept

April 5, 2017 updated by: Amgen

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

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).

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

19

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Duncansville, Pennsylvania, United States, 16635
        • Research Site
    • Texas
      • Dallas, Texas, United States, 75231
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

45 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Etanercept + Denosumab
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
Administered by subcutaneous injection once a week
Other Names:
  • Enbrel®
Drug: Denosumab
Administered by subcutaneous injection
Other Names:
  • Prolia®

What is the study measuring?

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
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.
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
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.
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
Time Frame
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.
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
Time Frame: Prior to etanercept and denosumab dose administrations, as applicable, on days 8, 22, and 29
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
Time Frame: Baseline (Day 8) and Days 22, 29, 85, and 176
Baseline (Day 8) and Days 22, 29, 85, and 176

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Amgen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2011

Primary Completion (Actual)

January 1, 2016

Study Completion (Actual)

January 1, 2016

Study Registration Dates

First Submitted

January 13, 2011

First Submitted That Met QC Criteria

February 10, 2011

First Posted (Estimate)

February 11, 2011

Study Record Updates

Last Update Posted (Actual)

June 20, 2017

Last Update Submitted That Met QC Criteria

April 5, 2017

Last Verified

April 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20101324

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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