The Effects of Denosumab on the Pharmacokinetics (PK) of Midazolam
9. juli 2018 opdateret af: 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.
Studieoversigt
Status
Afsluttet
Betingelser
Intervention / Behandling
Detaljeret 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.
Undersøgelsestype
Interventionel
Tilmelding (Faktiske)
30
Fase
- Fase 1
Deltagelseskriterier
Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.
Berettigelseskriterier
Aldre berettiget til at studere
45 år til 75 år (Voksen, Ældre voksen)
Tager imod sunde frivillige
Ingen
Køn, der er berettiget til at studere
Kvinde
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
Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
|---|---|
|
Andet: Midazolam
All 27 subjects will receive midazolam.
|
Eighteen (18) subjects will receive 1 fixed dose administration of denosumab.
Andre navne:
|
|
Aktiv komparator: Denosumab
Eighteen (18) subjects will receive denosumab.
|
All subjects will receive two oral dose administrations of midazolam.
|
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
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 |
Foranstaltningsbeskrivelse |
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
|
Samarbejdspartnere og efterforskere
Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.
Sponsor
Publikationer og nyttige links
Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.
Hjælpsomme links
Datoer for undersøgelser
Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.
Studer store datoer
Studiestart
1. november 2010
Primær færdiggørelse (Faktiske)
1. juli 2011
Studieafslutning (Faktiske)
1. juli 2011
Datoer for studieregistrering
Først indsendt
14. oktober 2010
Først indsendt, der opfyldte QC-kriterier
14. oktober 2010
Først opslået (Skøn)
15. oktober 2010
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
7. august 2018
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
9. juli 2018
Sidst verificeret
1. september 2015
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Yderligere relevante MeSH-vilkår
- Metaboliske sygdomme
- Muskuloskeletale sygdomme
- Knoglesygdomme
- Knoglesygdomme, metaboliske
- Osteoporose
- Osteoporose, postmenopausal
- Lægemidlers fysiologiske virkninger
- Neurotransmittermidler
- Molekylære mekanismer for farmakologisk virkning
- Depressive midler til centralnervesystemet
- Bedøvelsesmidler, intravenøst
- Bedøvelsesmidler, general
- Bedøvelsesmidler
- Beroligende midler
- Psykotropiske stoffer
- Hypnotika og beroligende midler
- Adjuvanser, anæstesi
- Anti-angst midler
- GABA modulatorer
- GABA agenter
- Knogletæthedsbevarende midler
- Midazolam
- Denosumab
Andre undersøgelses-id-numre
- 20101131
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