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

NCT ID: NCT01221727

Last Updated: 2018-08-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-11-30
• Study Completion Date: 2011-07-31

Brief Summary

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

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.

Conditions

Postmenopausal Osteoporosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Midazolam

All 27 subjects will receive midazolam.

Group Type: OTHER

Denosumab

Intervention Type: DRUG

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

Denosumab

Eighteen (18) subjects will receive denosumab.

Group Type: ACTIVE_COMPARATOR

Midazolam

Intervention Type: DRUG

All subjects will receive two oral dose administrations of midazolam.

Interventions

Denosumab

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

Intervention Type: DRUG

Midazolam

All subjects will receive two oral dose administrations of midazolam.

Intervention Type: DRUG

Other Intervention Names

AMG 162

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

• Minimum Eligible Age: 45 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Amgen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

MD

Role: STUDY_DIRECTOR

Amgen

References

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.

Reference Type: BACKGROUND

PMID: 25505582 (View on PubMed)

Related Links

http://www.amgentrials.com

AmgenTrials clinical trials website

Other Identifiers

20101131

Identifier Type: -

Identifier Source: org_study_id