The Effects of Denosumab on the Pharmacokinetics (PK) of Midazolam

Amgen30 enrolled

Overview

This is a multi-center, open-label, drug-drug interaction study in postmenopausal women with osteoporosis.

Approximately 27 subjects (Group A: 18; Group B: 9) will receive a 2 mg oral dose of midazolam on day 1 followed by a 24 hour PK collection. Subjects randomized to Group A will receive a single 60 mg subcutaneous (SC) dose of denosumab on day 2 administered in the abdomen. On study day 16, another 2 mg oral dose of midazolam will be administered to all subjects (Groups A and B) followed by a 24 hour PK collection. The primary analysis to determine the effect of denosumab on the PK of midazolam will be based on data from subjects in Group A only.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Postmenopausal Osteoporosis

Interventions

DenosumabDRUG

Eighteen (18) subjects will receive 1 fixed dose administration of denosumab.

MidazolamDRUG

All subjects will receive two oral dose administrations of midazolam.

Eligibility

Sex: FEMALEMin age: 45 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Between 45 to 75 years of age * Postmenopausal women * Osteoporosis Exclusion Criteria: * Use of any known inhibitors of cytochrome P450 3A4/P-gp (CYP3A4) within 14 days or 5 half lives, whichever is longer; or grapefruit juice or grapefruit containing products within 7 days prior to investigational product administration * Use of any known CYP3A4 inducers within 30 days or 5 half-lives, whichever is longer, prior to investigational product administration * Use of any herbal medicine with a known impact on CYP3A4 (eg, St. John's wort) within 30 days prior to investigational product administration * Current use of medications prescribed for osteoporosis treatment * Use of midazolam within 14 days prior to investigational product administration * Influenza or other vaccination within 28 days of screening * Previous exposure to denosumab

Outcomes

Primary Outcomes

Ratio of Pharmcokinetic (PK) Area Under the Concentration Time Curve (AUC) Parameter Estimates Between Day 16 (Midazolam With the Presence of Denosumab) and Day 1 (Midazolam Only)

The ratio and confidence interval are calculated based on natural log scale data and converted back to the original scale.