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ID
Source
Brief title
Health condition
Interstitial Lung disease
Sponsors and support
Intervention
Outcome measures
Primary outcome
Change in nintedanib bioavailability, expressed in area under the plasma curve (AUC).
Secondary outcome
Change in other pharmacokinetic parameters i.e. maximal concentration (Cmax) and time to reach Cmax (Tmax) and a difference in occurrence of (patient reported) toxicity.
Background summary
Rationale: Tyrosine kinase inhibitors (TKIs) have become essential in the treatment of various diseases. Nintedanib (Ofev ®) is registered as first-line treatment of fibrotic interstitial lung disease (ILD). Nintedanib’s bioavailability is 4.7% and is a substrate of the efflux pump P-glycoprotein (P-gP). P-gP can be inhibited by flavonoids, especially by epigallocatechin gallate (EGCG). ECGC is highly concentrated found in the popular beverage green tea. Hence, the flavonoid-drug interaction could potentially lead to higher nintedanib absorption by the gastro-intestinal tract. This would cause higher systemic bioavailability and lower local gastro-intestinal drug concentrations (which is thought to be causing most of nintedanib’s toxicity). Furthermore, inter-patient variability could decrease.
Objective: to study the pharmacokinetic interaction between nintedanib and green tea extract (with > 60% ECGC) in fibrotic ILD patients.
Study design: A randomized, two-phase cross-over pharmacokinetic study in which nintedanib will be taken twice daily for seven days with water and a meal respectively with or without 500 mg green tea extract (with > 60% ECGC).
Study population: Adult patients who (are planned to) receive nintedanib for an ILD.
Main study parameters/endpoints: Primary outcome will be the change in nintedanib bioavailability, expressed in area under the plasma curve (AUC). Secondary objectives are the change in other pharmacokinetic parameters i.e. maximal concentration (Cmax) and time to reach Cmax (Tmax) and a difference in occurrence of (patient reported) toxicity.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The risk of the blood withdrawals is negligible.
Study objective
The flavonoid-drug interaction could potentially lead to higher nintedanib absorption by the gastro-intestinal tract. This would cause higher systemic bioavailability and lower local gastro-intestinal drug concentrations. Furthermore, inter-patient variability could decrease, as also seen with other SMKI’s.
Study design
Interim analysis after four evaluable patients, full analysis of primary and secondary endpoints after last evaluable inclusion. Plasma drug concentrations are measured with LC/MS-MS.
Intervention
Seven days nintedanib taken with 500 mg green tea extract (with > 60% ECGC)
Inclusion criteria
- Age ≥18 years;
- Able to understand the written information and able to give informed consent;
- Planned treatment with nintedanib for any fibrotic ILD according to standard of care.
Exclusion criteria
- unable to draw blood for study purposes
- usage of other strong P-gP or CYP3A4 interacting compounds
- patients with known impaired drug absorption (e.g. gastrectomy and achlorhydria)
Design
Recruitment
IPD sharing statement
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| NTR-new | NL8913 |
| Other | METC Erasmus MC : MEC 20-558 |