Effects of Denosumab on the Pharmacokinetics of Etanercept

NCT01294397 | Terminated Phase 1 Results

• 1 other identifier: 20101324
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 2

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).

Conditions

Postmenopausal; Osteopenia; Rheumatoid Arthritis; Osteoporosis

Keywords

Amgen; Phase 1; Postmenopausal; Osteopenia; Rheumatoid; Bone Mineral Density; Arthritis; Pharmacokinetics; Osteoporosis

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (3)

• 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

Study Arms (1)

Etanercept + Denosumab

EXPERIMENTAL

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; Drug: Denosumab

Interventions

Etanercept DRUG

Administered by subcutaneous injection once a week

Also known as: Enbrel®

Etanercept + Denosumab

Denosumab DRUG

Administered by subcutaneous injection

Also known as: Prolia®

Etanercept + Denosumab

Eligibility Criteria

• Age: 45 Years - 80 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Amgen: lead

Study Sites (2)

Research Site

Duncansville, Pennsylvania, 16635, United States

Location

Research Site

Dallas, Texas, 75231, United States

Location

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Bone Diseases, Metabolic; Arthritis, Rheumatoid; Osteoporosis; Arthritis

Interventions

Etanercept; Denosumab

Condition Hierarchy (Ancestors)

Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Joint Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Immunoglobulin Fc Fragments; Immunoglobulin Fragments; Peptide Fragments; Peptides; Amino Acids, Peptides, and Proteins; Immunoglobulin Constant Regions; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Receptors, Tumor Necrosis Factor; Receptors, Cytokine; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 13, 2011
• First Posted: February 11, 2011
• Study Start: March 1, 2011
• Primary Completion: January 1, 2016
• Study Completion: January 1, 2016
• Last Updated: June 20, 2017
• Results First Posted: June 20, 2017

Record last verified: 2017-04

Locations

US (2)