The Effects of Denosumab on the Pharmacokinetics (PK) of Midazolam
Information source: Amgen
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Postmenopausal Osteoporosis
Intervention: Denosumab (Drug); Midazolam (Drug)
Phase: Phase 1
Status: Completed
Sponsored by: Amgen Official(s) and/or principal investigator(s): MD, Study Director, Affiliation: Amgen
Summary
This is a multi-center, open-label, drug-drug interaction study in postmenopausal women with
osteoporosis.
Clinical Details
Official title: The Effects of Denosumab on the Pharmacokinetics (PK) of Midazolam, a Cytochrome P450 3A4/P-gp (CYP3A4) Substrate, in Postmenopausal Osteoporotic Women
Study design: Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: 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)Estimates of Inter- and Intra-subject Variability for the PK AUC Parameters for Midazolam With Denosumab Group Estimates of Inter- and Intra-subject Variability for PK Maximum Observed Plasma Concentration (Cmax) Parameter for Midazolam With Denosumab Group Ratio of PK Cmax Parameter Estimates Between Day 16 (Midazolam With the Presence of Denosumab) and Day 1 (Midazolam Only)
Secondary outcome: Ratio of PK AUC Parameter Estimates Between Day 16 (Midazolam Only) and Day 1(Midazolam Only)Estimates of Inter- and Intra-subject Variability for the PK AUC Parameters for Midazolam Only Group Estimates of Inter- and Intra-subject Variability for PK Cmax Parameter for Midazolam Only Group Summary of Serum Denosumab Concentration Summary of Serum C-Telopeptide Concentration Summary of Percent Change From Baseline to Day 16 for Serum C-Telopeptide Concentration Ratio of PK Cmax Parameter Estimates Between Day 16 (Midazolam Only) and Day 1(Midazolam Only)
Detailed description:
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.
Eligibility
Minimum age: 45 Years.
Maximum age: 75 Years.
Gender(s): Female.
Criteria:
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
Locations and Contacts
Additional Information
AmgenTrials clinical trials website
Related publications: Jang G, Kaufman A, Lee E, Hamilton L, Hutton S, Egbuna O, Padhi D. A clinical therapeutic protein drug-drug interaction study: coadministration of denosumab and midazolam in postmenopausal women with osteoporosis. Pharmacol Res Perspect. 2014 Apr;2(2):e00033. doi: 10.1002/prp2.33. Epub 2014 Mar 13.
Starting date: November 2010
Last updated: July 18, 2014
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