The Effects of Denosumab on the Pharmacokinetics (PK) of Midazolam
9. juli 2018 oppdatert av: Amgen
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.
Studieoversikt
Status
Fullført
Forhold
Intervensjon / Behandling
Detaljert beskrivelse
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.
Studietype
Intervensjonell
Registrering (Faktiske)
30
Fase
- Fase 1
Deltakelseskriterier
Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
45 år til 75 år (Voksen, Eldre voksen)
Tar imot friske frivillige
Nei
Kjønn som er kvalifisert for studier
Hunn
Beskrivelse
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
Studieplan
Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
|
Annen: Midazolam
All 27 subjects will receive midazolam.
|
Eighteen (18) subjects will receive 1 fixed dose administration of denosumab.
Andre navn:
|
|
Aktiv komparator: Denosumab
Eighteen (18) subjects will receive denosumab.
|
All subjects will receive two oral dose administrations of midazolam.
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
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)
Tidsramme: 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.
|
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
Tidsramme: 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
|
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
Tidsramme: 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
|
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)
Tidsramme: 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.
|
From day 1 pre-dose to 24 hours post-dose and from day 16 pre-dose to 24 hours post-dose
|
Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Ratio of PK AUC Parameter Estimates Between Day 16 (Midazolam Only) and Day 1(Midazolam Only)
Tidsramme: 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.
|
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
Tidsramme: 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.
|
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
Tidsramme: 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.
|
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
Tidsramme: Baseline (day 2 pre-dose) to day 16
|
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.
|
Baseline (day 2 pre-dose) to day 16
|
|
Summary of Serum C-Telopeptide Concentration
Tidsramme: Baseline (day 2 pre-dose) to day 16
|
This table summarizes serum C-Telopeptide (sCTX) concentration raw values for Midazolam with Denosumab group.
|
Baseline (day 2 pre-dose) to day 16
|
|
Summary of Percent Change From Baseline to Day 16 for Serum C-Telopeptide Concentration
Tidsramme: Baseline (day 2 pre-dose) to day 16
|
This table summarizes percent change from baseline to day 16 for serum C-Telopeptide (sCTX) concentration raw values for Midazolam with Denosumab group.
|
Baseline (day 2 pre-dose) to day 16
|
|
Ratio of PK Cmax Parameter Estimates Between Day 16 (Midazolam Only) and Day 1(Midazolam Only)
Tidsramme: 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.
|
From day 1 pre-dose to 24 hours post-dose and from day 16 pre-dose to 24 hours post-dose
|
Samarbeidspartnere og etterforskere
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Sponsor
Publikasjoner og nyttige lenker
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Hjelpsomme linker
Studierekorddatoer
Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.
Studer hoveddatoer
Studiestart
1. november 2010
Primær fullføring (Faktiske)
1. juli 2011
Studiet fullført (Faktiske)
1. juli 2011
Datoer for studieregistrering
Først innsendt
14. oktober 2010
Først innsendt som oppfylte QC-kriteriene
14. oktober 2010
Først lagt ut (Anslag)
15. oktober 2010
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
7. august 2018
Siste oppdatering sendt inn som oppfylte QC-kriteriene
9. juli 2018
Sist bekreftet
1. september 2015
Mer informasjon
Begreper knyttet til denne studien
Nøkkelord
Ytterligere relevante MeSH-vilkår
- Metabolske sykdommer
- Muskel- og skjelettsykdommer
- Beinsykdommer
- Bensykdommer, metabolske
- Osteoporose
- Osteoporose, postmenopausal
- Fysiologiske effekter av legemidler
- Nevrotransmittere agenter
- Molekylære mekanismer for farmakologisk virkning
- Sentralnervesystemdepressiva
- Anestesimidler, intravenøst
- Anestesimidler, general
- Bedøvelsesmidler
- Beroligende midler
- Psykotropiske stoffer
- Hypnotika og beroligende midler
- Adjuvanser, anestesi
- Anti-angst midler
- GABA modulatorer
- GABA-agenter
- Bone Density Conservation Agents
- Midazolam
- Denosumab
Andre studie-ID-numre
- 20101131
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