Postmenopausal OsteoporosisPhase 1NCT01221727
The Effects of Denosumab on the Pharmacokinetics (PK) of Midazolam
A Phase 1 study testing Denosumab and Midazolam in people with Postmenopausal Osteoporosis, run by Amgen.
Trial summary
This is a multi-center, open-label, drug-drug interaction study in postmenopausal women with osteoporosis. Read more about this study
- Who is it for?
- Ages 45 to 75 years, women only
- Conditions the study is for
- Postmenopausal Osteoporosis
- What is being tested?
- Denosumab and Midazolam
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- No sites listed yet
- Study dates
- Nov 2010to Jul 2011
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 to 75 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Between 45 to 75 years of age
- Postmenopausal women
- Osteoporosis
Who cannot join
- 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
About this study
Official title: The Effects of Denosumab on the Pharmacokinetics (PK) of Midazolam, a Cytochrome P450 3A4/P-gp (CYP3A4) Substrate, in Postmenopausal Osteoporotic Women
This is a multi-center, open-label, drug-drug interaction study in postmenopausal women with osteoporosis.
Read the 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
- Being tested
- Denosumab, Midazolam
- Keywords
- Amgen, Phase 1, Postmenopausal, Osteoporosis
- Medical subject headings
- Osteoporosis, Postmenopausal, Osteoporosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DenosumabDrug
Also called AMG 162
Eighteen (18) subjects will receive 1 fixed dose administration of denosumab.
MidazolamDrug
All subjects will receive two oral dose administrations of midazolam.
| Study group | Role | What they receive |
|---|---|---|
| Midazolam | Other | All 27 subjects will receive midazolam. Receives: Drug: Denosumab |
| Denosumab | Active comparator | Eighteen (18) subjects will receive denosumab. Receives: Drug: Midazolam |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Measured: 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
Measured: 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.
Measured: 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)
The ratio and confidence interval are calculated based on natural log scale data and converted back to the original scale.
Measured: 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
AUC Subject denotes the inter-subject variability, while AUC Residual denotes the intra-subject variability.
Measured: 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
Cmax Subject denotes the inter-subject variability, while Cmax Residual denotes the intra-subject variability.
Measured: 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
This table summarizes serum Denosumab for Midazolam with Denosumab group. The Lower Limit Of Quantification (LLOQ) is 20 ng/mL. On Day 2 (pre-dose), the true value is below LLOQ, and is treated as 0 in the analysis.
Measured: Baseline (day 2 pre-dose) to day 16
Summary of Serum C-Telopeptide Concentration
This table summarizes serum C-Telopeptide (sCTX) concentration raw values for Midazolam with Denosumab group.
Measured: Baseline (day 2 pre-dose) to day 16
Summary of Percent Change From Baseline to Day 16 for Serum C-Telopeptide Concentration
This table summarizes percent change from baseline to day 16 for serum C-Telopeptide (sCTX) concentration raw values for Midazolam with Denosumab group.
Measured: Baseline (day 2 pre-dose) to day 16
Ratio of PK Cmax Parameter Estimates Between Day 16 (Midazolam Only) 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.
Measured: From day 1 pre-dose to 24 hours post-dose and from day 16 pre-dose to 24 hours post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Oct 2010 (estimated)
- Study startNov 2010
- Primary completionJul 2011
- Study completionJul 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Postmenopausal OsteoporosisStudies of the same condition, open and under way.
- More trials run by AmgenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amgen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01221727
- Sponsor's protocol ID
- 20101131
- Status last verified
- Sep 2015
- First submitted
- 14 Oct 2010
- Last updated
- 7 Aug 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
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.
PubMed 25505582
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of Denosumab on the Pharmacokinetics (PK) of Midazolam, a Cytochrome P450 3A4/P-gp (CYP3A4) Substrate, in Postmenopausal Osteoporotic Women
- ClinicalTrials.gov ID
- NCT01221727
- Acronym / sponsor ID
- 20101131
- Conditions
- Postmenopausal Osteoporosis
- Keywords
- Amgen, Phase 1, Postmenopausal, Osteoporosis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Study start
- Nov 2010
- Primary completion
- Jul 2011 (actual)
- Study completion
- Jul 2011 (actual)
- First posted
- 15 Oct 2010 (estimated)
- Results
- Posted 7 Nov 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Midazolam | Other | Drug: DenosumabAll 27 subjects will receive midazolam. |
| Denosumab | Active comparator | Drug: MidazolamEighteen (18) subjects will receive denosumab. |
Who may qualify
- Ages
- 45 to 75 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Between 45 to 75 years of age
- Postmenopausal women
- Osteoporosis
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DenosumabAlso: AMG 162Eighteen (18) subjects will receive 1 fixed dose administration of denosumab. | Drug | Midazolam |
| MidazolamAll subjects will receive two oral dose administrations of midazolam. | Drug | Denosumab |
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)
Time frame: From day 1 pre-dose to 24 hours post-dose and from day 16 pre-dose to 24 hours post-dose
The ratio and confidence interval are calculated based on natural log scale data and converted back to the original scale.
Estimates of Inter- and Intra-subject Variability for the PK AUC Parameters for Midazolam With Denosumab Group
Time frame: From day 1 pre-dose to 24 hours post-dose and from day 16 pre-dose to 24 hours post-dose
AUC Subject denotes the inter-subject variability, while AUC Residual denotes the intra-subject variability
Estimates of Inter- and Intra-subject Variability for PK Maximum Observed Plasma Concentration (Cmax) Parameter for Midazolam With Denosumab Group
Time frame: From day 1 pre-dose to 24 hours post-dose and from day 16 pre-dose to 24 hours post-dose
Cmax Subject denotes the inter-subject variability, while Cmax Residual denotes the intra-subject variability
Ratio of PK Cmax Parameter Estimates Between Day 16 (Midazolam With the Presence of Denosumab) and Day 1 (Midazolam Only)
Time frame: From day 1 pre-dose to 24 hours post-dose and from day 16 pre-dose to 24 hours post-dose
The ratio and confidence interval are calculated based on natural log scale data and converted back to the original scale.
7 secondary outcomes
Ratio of PK AUC Parameter Estimates Between Day 16 (Midazolam Only) and Day 1(Midazolam Only)
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Baseline (day 2 pre-dose) to day 16
Summary of Serum C-Telopeptide Concentration
Time frame: Baseline (day 2 pre-dose) to day 16
Summary of Percent Change From Baseline to Day 16 for Serum C-Telopeptide Concentration
Time frame: Baseline (day 2 pre-dose) to day 16
Ratio of PK Cmax Parameter Estimates Between Day 16 (Midazolam Only) and Day 1(Midazolam Only)
Time frame: From day 1 pre-dose to 24 hours post-dose and from day 16 pre-dose to 24 hours post-dose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 25505582Jang 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.
- AmgenTrials clinical trials websiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MD study director
Amgen
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Denosumab and Midazolam in people with Postmenopausal Osteoporosis, run by Amgen.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Nov 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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) (time frame: From day 1 pre-dose to 24 hours post-dose and from day 16 pre-dose to 24 hours post-dose). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01221727, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Aug 2018.