Drug Cocktail Interaction Study of St. John's Wort Dry Extract Ze 117

Study Overview
=================
Brief Summary
-----------------
This Study evaluates the Effect of St. John's Wort dry Extract Ze 117 on Several Cytochrome P450 Enzymes and on Transporter P-Glycoprotein in Healthy Volunteers.

Detailed Description
-----------------
Current data indicate that St. John's wort preparations may induce hepatic cytochrome P450 enzymes and transport proteins. This can result in drug interactions. The study design is standard for DDI studies and is based on the regulatory guidance of the Food and Drug Administration (FDA) and of the European Medicines Agency (EMA). A cocktail approach involving the administration of multiple cytochrome P450 (CYP)- or P-glycoprotein (P-gp)-specific probe drugs is used to simultaneously assess the activities of these enzymes and the transporter P-gp.

Official Title
-----------------
Drug Cocktail Interaction Study to Investigate the Effect of St. John's Wort Dry Extract Ze 117 on Several Cytochrome P450 Enzymes and on Transporter P-Glycoprotein in Healthy Volunteers

Conditions
-----------------
Drug Interaction Study

Intervention / Treatment
-----------------
* Drug: Ze 117
* Drug: Probe drug cocktail


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: written informed consent Caucasian male or female subjects aged between ≥18 and ≤55years Physically and mentally healthy BMI between ≥19 and ≤29 kg/m2, and body weight ≤90 kg Non-smoker If female, the pregnancy test at screening and at admission must be negative Exclusion Criteria: Known or suspected hypersensitivity to study drugs history of, any clinically significant diseases Positive test of hepatitis B, hepatitis C or HIV Screening Known photohypersensitivity

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: open-label, non-randomized, single-sequence study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Probe drug cocktail / Ze 117<br>One-sequence, Probe drug cocktail alone and in combination with Ze 117. | Drug: Ze 117<br>* Subjects will be hospitalized to receive a probe drug cocktail alone and in combination with Ze 117.<br>* Other names: St. John's wort dry extract Ze 117;Drug: Probe drug cocktail<br>* Subjects will be hospitalized to receive a probe drug cocktail alone and in combination with Ze 117.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the Plasma concentration versus time curve (AUC0-t) | Pharmacokinetic Parameter AUC0-t (mg*h/L) of the probe drugs will be determined. | 72 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the Plasma concentration versus time curve (AUC0-inf) | Pharmacokinetic parameter (mg*h/L) of the probe drugs and their metabolites will be determined. | 72 hours | 
| Peak Plasma Concentration (Cmax) | Pharmacokinetic Parameter (ng/ml) of the probe drugs and their metabolites will be determined. | 72 hours | 
| Elimination rate constant (Ke) | Pharmacokinetic Parameter (h^-1) of the probe drugs and their metabolites will be determined. | 72 hours | 
| Elimination half life (t1/2) | Pharmacokinetic Parameter (h) of the probe drugs and their metabolites will be determined. | 72 hours |