Ignite Creation Date:
2025-12-24 @ 4:30 PM
Ignite Modification Date:
2025-12-24 @ 4:30 PM
Study NCT ID:
NCT03886766
Status:
COMPLETED
Last Update Posted:
2024-12-20
First Post:
2019-03-20
Is Possible Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Bioavailability Mechanistic Study of Hot-Melt Extruded Amorphous Solid Dispersions
Sponsor:
University Hospital, Basel, Switzerland
Organization:
Study Overview
Official Title:
Bioavailability Mechanistic Study of Hot-Melt-Extruded Amorphous Solid Dispersions
Status:
COMPLETED
Status Verified Date:
2021-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
BEAD
Brief Summary:
It is the aim of the study to investigate the functioning of a drug delivery system (drug-rich particles forming hot-melt extruded amorphous solid dispersions) with respect to mechanisms of bioavailability of poorly soluble drug substances.
Detailed Description:
Poor drug solubility, and therefore low bioavailability, remains a problem in drug development that causes many drug candidates to drop out during drug development. Bioavailability is linked to drug solubility and intestinal permeability. A promising method to increase drug solubility, and therefore bioavailability, is the formulation of the drug as hot-melt extruded amorphous solid dispersion drug delivery systems, which have been shown to potentially increase in vivo and clinical bioavailability.The mechanisms that lead to increased bioavailability are not understood completely.
In this study, investigators investigate the role of amorphous solid dispersions and thereof generated drug-rich particles on bioavailability and their in vivo behaviour. Investigators do so by administering the delivery system at different stages in the process of drug availability.
Primary objectives are the pharmacokinetic analysis of a model formulation using efavirenz as model drug tracer in human.
* Comparison of pharmacokinetic parameters such as relative bioavailability and further parameters derived from pharmacokinetic analysis and corresponding interpatient variabilities.
* Mechanistic analysis of pharmacokinetic data, such as determination of in vivo dissolution from the solid formulation (study product 1) to drug rich particles (study product 2) using numerical deconvolution or analysis of the effect of drug rich particles on the absorption rate of Efavirenz in comparison to the solution of Efavirenz (study product 3).
Secondary objectives are the comparison of obtained pharmacokinetic profiles to existing data of a conventional formulation with respect to:
* Comparison of pharmacokinetic parameters such as relative bioavailability and further parameters derived from pharmacokinetic analysis and corresponding interpatient variabilities.
* Extrapolation investigation from in vitro to in vivo data.
Safety objectives are the recording of any side effects or tolerability issues of the investigational drug delivery system.
In this study, investigators investigate the role of amorphous solid dispersions and thereof generated drug-rich particles on bioavailability and their in vivo behaviour. Investigators do so by administering the delivery system at different stages in the process of drug availability.
Primary objectives are the pharmacokinetic analysis of a model formulation using efavirenz as model drug tracer in human.
* Comparison of pharmacokinetic parameters such as relative bioavailability and further parameters derived from pharmacokinetic analysis and corresponding interpatient variabilities.
* Mechanistic analysis of pharmacokinetic data, such as determination of in vivo dissolution from the solid formulation (study product 1) to drug rich particles (study product 2) using numerical deconvolution or analysis of the effect of drug rich particles on the absorption rate of Efavirenz in comparison to the solution of Efavirenz (study product 3).
Secondary objectives are the comparison of obtained pharmacokinetic profiles to existing data of a conventional formulation with respect to:
* Comparison of pharmacokinetic parameters such as relative bioavailability and further parameters derived from pharmacokinetic analysis and corresponding interpatient variabilities.
* Extrapolation investigation from in vitro to in vivo data.
Safety objectives are the recording of any side effects or tolerability issues of the investigational drug delivery system.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: