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

NCT01221727 | Completed Phase 1 Results

• 1 other identifier: 20101131
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief Summary

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

Conditions

Postmenopausal Osteoporosis

Keywords

Amgen; Phase 1; Postmenopausal; Osteoporosis

Outcome Measures

Primary Outcomes (4)

• 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.

  From day 1 pre-dose to 24 hours post-dose and from day 16 pre-dose to 24 hours post-dose

• Estimates of Inter- and Intra-subject Variability for the PK AUC Parameters for Midazolam With Denosumab Group

  AUC Subject denotes the inter-subject variability, while AUC Residual denotes the intra-subject variability

  From day 1 pre-dose to 24 hours post-dose and from day 16 pre-dose to 24 hours post-dose

• Estimates of Inter- and Intra-subject Variability for PK Maximum Observed Plasma Concentration (Cmax) Parameter for Midazolam With Denosumab Group

  Cmax Subject denotes the inter-subject variability, while Cmax Residual denotes the intra-subject variability

  From day 1 pre-dose to 24 hours post-dose and from day 16 pre-dose to 24 hours post-dose

• Ratio of PK Cmax 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.

  From day 1 pre-dose to 24 hours post-dose and from day 16 pre-dose to 24 hours post-dose

Secondary Outcomes (7)

• Ratio of PK AUC Parameter Estimates Between Day 16 (Midazolam Only) and Day 1(Midazolam Only)

  From day 1 pre-dose to 24 hours post-dose and from day 16 pre-dose to 24 hours post-dose

• Estimates of Inter- and Intra-subject Variability for the PK AUC Parameters for Midazolam Only Group

  From day 1 pre-dose to 24 hours post-dose and from day 16 pre-dose to 24 hours post-dose

• Estimates of Inter- and Intra-subject Variability for PK Cmax Parameter for Midazolam Only Group

  From day 1 pre-dose to 24 hours post-dose and from day 16 pre-dose to 24 hours post-dose

• Summary of Serum Denosumab Concentration

  Baseline (day 2 pre-dose) to day 16

• Summary of Serum C-Telopeptide Concentration

  Baseline (day 2 pre-dose) to day 16

Study Arms (2)

Midazolam

OTHER

All 27 subjects will receive midazolam.

Drug: Denosumab

Denosumab

ACTIVE COMPARATOR

Eighteen (18) subjects will receive denosumab.

Drug: Midazolam

Interventions

Denosumab DRUG

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

Also known as: AMG 162

Midazolam

Midazolam DRUG

All subjects will receive two oral dose administrations of midazolam.

Denosumab

Eligibility Criteria

• Age: 45 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Between 45 to 75 years of age
• Postmenopausal women
• Osteoporosis

You may not qualify if:

• 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

Sponsors & Collaborators

• Amgen: lead

Related Publications (1)

• 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.

  PMID: 25505582 BACKGROUND

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Osteoporosis, Postmenopausal; Osteoporosis

Interventions

Denosumab; Midazolam

Condition Hierarchy (Ancestors)

Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 14, 2010
• First Posted: October 15, 2010
• Study Start: November 1, 2010
• Primary Completion: July 1, 2011
• Study Completion: July 1, 2011
• Last Updated: August 7, 2018
• Results First Posted: November 7, 2013

Record last verified: 2015-09