Effects of Denosumab on the Pharmacokinetics of Etanercept

Amgen

Status and phase: Terminated; Phase 1

Conditions: Osteoporosis; Osteopenia; Postmenopausal; Rheumatoid Arthritis

Treatments: Drug: Denosumab; Drug: Etanercept

Study type: Interventional

Funder types: Industry

Identifiers

NCT01294397

20101324

Details and patient eligibility

About

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).

Enrollment: 19 patients

Sex: Female

Ages: 45 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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19 participants in 1 patient group

Etanercept + Denosumab

Experimental group

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.

Treatment:

Drug: Etanercept

Drug: Denosumab