Clinical trial NCT01294397: Effects of Denosumab on the Pharmacokinetics of Etanercept
Official title: The Effects of Denosumab on the Pharmacokinetics of Etanercept in Postmenopausal Women With Low Bone Mineral Density and Rheumatoid Arthritis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Postmenopausal
Osteopenia
Rheumatoid Arthritis
Osteoporosis
Keywords: Amgen
Phase 1
Postmenopausal
Osteopenia
Rheumatoid
Bone Mineral Density
Arthritis
Pharmacokinetics
Osteoporosis
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2011-02-11
Enrollment: 19
Sex: FEMALE
Minimum age (years): 45
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


Eligibility criteria: 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

Primary outcomes:
measure: Area Under the Serum Concentration-time Curve From 0 to 168 Hours (AUC0-168) for Etanercept
timeFrame: Day 1 and day 22; at each time point samples were taken predose and 2, 3, 4, 5, 6 and 8 days postdose.
measure: Maximum Observed Serum Concentration (Cmax) of Etanercept
timeFrame: 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:
measure: Time to Maximum Serum Concentration (Tmax) of Etanercept
timeFrame: Day 1 and day 22; at each time point samples were taken predose and 2, 3, 4, 5, 6 and 8 days postdose.
measure: Serum Denosumab Concentration
timeFrame: Prior to etanercept and denosumab dose administrations, as applicable, on days 8, 22, and 29
measure: Percent Change From Baseline in Serum C-telopeptide (sCTx) Concentrations
timeFrame: Baseline (Day 8) and Days 22, 29, 85, and 176
Other outcomes:
Locations:
city: Duncansville
country: United States
facility: Research Site
state: Pennsylvania
city: Dallas
country: United States
facility: Research Site
state: Texas
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: