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

Amgen

Status and phase

Completed

Phase 1

Conditions

Postmenopausal Osteoporosis

Treatments

Drug: Denosumab

Drug: Midazolam

Study type

Interventional

Funder types

Industry

Identifiers

NCT01221727

20101131

Details and patient eligibility

About

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

Full 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.

Enrollment

30 patients

Sex

Female

Ages

45 to 75 years old

Volunteers

No Healthy Volunteers

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