Effects of Denosumab on the Pharmacokinetics of Etanercept

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01294397
Recruitment Status : Terminated (Lack of enrollment.)
First Posted : February 11, 2011
Results First Posted : June 20, 2017
Last Update Posted : June 20, 2017
Information provided by (Responsible Party):

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).

Condition or disease Intervention/treatment Phase
Postmenopausal Osteopenia Rheumatoid Arthritis Osteoporosis Drug: Etanercept Drug: Denosumab Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 19 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: The Effects of Denosumab on the Pharmacokinetics of Etanercept in Postmenopausal Women With Low Bone Mineral Density and Rheumatoid Arthritis
Study Start Date : March 2011
Actual Primary Completion Date : January 2016
Actual Study Completion Date : January 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Arthritis Minerals
U.S. FDA Resources

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 Name: Enbrel®
Drug: Denosumab
Administered by subcutaneous injection
Other Name: Prolia®

Primary Outcome Measures :
  1. 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).

  2. 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 Measures :
  1. 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. ]
  2. Serum Denosumab Concentration [ Time Frame: Prior to etanercept and denosumab dose administrations, as applicable, on days 8, 22, and 29 ]
  3. Percent Change From Baseline in Serum C-telopeptide (sCTx) Concentrations [ Time Frame: Baseline (Day 8) and Days 22, 29, 85, and 176 ]

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Ages Eligible for Study:   45 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01294397

United States, Pennsylvania
Research Site
Duncansville, Pennsylvania, United States, 16635
United States, Texas
Research Site
Dallas, Texas, United States, 75231
Sponsors and Collaborators
Study Director: MD Amgen

Additional Information:
Responsible Party: Amgen Identifier: NCT01294397     History of Changes
Other Study ID Numbers: 20101324
First Posted: February 11, 2011    Key Record Dates
Results First Posted: June 20, 2017
Last Update Posted: June 20, 2017
Last Verified: April 2017

Keywords provided by Amgen:
Phase 1
Bone Mineral Density

Additional relevant MeSH terms:
Arthritis, Rheumatoid
Bone Diseases, Metabolic
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Bone Diseases
Metabolic Diseases
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Gastrointestinal Agents
Immunosuppressive Agents
Immunologic Factors
Bone Density Conservation Agents