Phase 1 N=30 Randomized Treatment

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

Postmenopausal Osteoporosis

Bottom Line

View on ClinicalTrials.gov: NCT01221727 ↗

Enrolled (actual)

Serious AEs

0.0%

Results posted

Nov 2013

Primary outcome: Primary: 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) — 1.10; 1.12 unitless

Study Design & Population

Study type: Interventional
Phase: Phase 1
Interventions: Denosumab (Drug); Midazolam (Drug)
Age: Adult, Older Adult · 45+ yrs
Sex: Female
Sponsor: Amgen
Primary completion: Jul 2011

Outcome Measures

Outcome	Result	p-value
PRIMARY 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)	1.10; 1.12	—
PRIMARY Estimates of Inter- and Intra-subject Variability for the PK AUC Parameters for Midazolam With Denosumab Group	0.19; 0.07; 0.21; 0.08	—
PRIMARY Estimates of Inter- and Intra-subject Variability for PK Maximum Observed Plasma Concentration (Cmax) Parameter for Midazolam With Denosumab Group	0.15; 0.07	—
PRIMARY Ratio of PK Cmax Parameter Estimates Between Day 16 (Midazolam With the Presence of Denosumab) and Day 1 (Midazolam Only)	1.11	—
SECONDARY Ratio of PK AUC Parameter Estimates Between Day 16 (Midazolam Only) and Day 1(Midazolam Only)	0.98; 0.98	—
SECONDARY Estimates of Inter- and Intra-subject Variability for the PK AUC Parameters for Midazolam Only Group	0.27; 0.03; 0.31; 0.03	—
SECONDARY Estimates of Inter- and Intra-subject Variability for PK Cmax Parameter for Midazolam Only Group	0.23; 0.06	—
SECONDARY Summary of Serum Denosumab Concentration	0; 5820; 5500	—
SECONDARY Summary of Serum C-Telopeptide Concentration	0.4655; 0.0606; -0.4079	—
SECONDARY Summary of Percent Change From Baseline to Day 16 for Serum C-Telopeptide Concentration	-87.52	—
SECONDARY Ratio of PK Cmax Parameter Estimates Between Day 16 (Midazolam Only) and Day 1(Midazolam Only)	1.05	—

Summary

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

Eligibility 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

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01221727). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.