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

Max Zeller Soehne AG20 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Drug Interaction Study

Interventions

Ze 117DRUG

Subjects will be hospitalized to receive a probe drug cocktail alone and in combination with Ze 117.

Probe drug cocktailDRUG

Subjects will be hospitalized to receive a probe drug cocktail alone and in combination with Ze 117.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 55 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (1)

Nuvisan GmbH

Neu-Ulm, Germany

Outcomes

Primary Outcomes

Ratio AUC0-t, Day 17 (Probe Drug Cocktail Plus Ze117 [Only at Day 17]) vs. Day 1 (Probe Drug Cocktail Alone)

The "number" as provided in the tables is the ratio (in %) of geometric LS means of AUC of day 17 dosing samples (probe drug cocktail plus Ze117) vs. Day 1 dosing samples (probe drug cocktail alone). A one-way ANOVA model (with terms for subject and treatment) was applied to analyze the effect of Ze117 on the respective probe drug. Log transformed (base e) parameters were used within the model. The estimated treatment difference between day 17 and day 1 was transformed back to original scale and presented as the ratio between treatments including the corresponding 90% confidence interval. Effect limits were predefined as follows: (1) Mild effect limits (50-200%), extended bioequivalence limits (70-143%), bioequivalence limits (80-125%).

Time frame: PK samples: pre-dose, and 10, 20, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 48 and 72 hours after each cocktail administration (at day 1 and day 17)

Secondary Outcomes

Ratio AUC0-t, Day 8 (Probe Drug Cocktail Plus Ze117 [Daily Throughout pk Sampling Period]) vs. Day 1 (Probe Drug Cocktail Alone)

The "number" as provided in the tables is the ratio (in %) of geometric LS means of AUC of day 8 dosing samples (probe drug cocktail plus Ze117) vs. Day 1 dosing samples (probe drug cocktail alone). A one-way ANOVA model (with terms for subject and treatment) was applied to analyze the effect of Ze117 on the respective probe drug. Log transformed (base e) parameters were used within the model. The estimated treatment difference between day 8 and day 1 was transformed back to original scale and presented as the ratio between treatments including the corresponding 90% confidence interval. Effect limits were predefined as follows: (1) Mild effect limits (50-200%), extended bioequivalence limits (70-143%), bioequivalence limits (80-125%).

Time frame: PK samples: pre-dose, and 10, 20, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 48 and 72 hours after each cocktail administration (at day 1 and day 8)

Ratio Cmax, Day 17 (Probe Drug Cocktail Plus Ze117 [Only at Day 17]) vs. Day 1 (Probe Drug Cocktail Alone)

Data from ClinicalTrials.gov

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Ratio Cmax, Day 8 (Probe Drug Cocktail Plus Ze117 [Daily Throughout pk Sampling Period]) vs. Day 1 (Probe Drug Cocktail Alone)

The "number" as provided in the tables is the ratio (in %) of geometric LS means of Cmax from day 8 dosing samples (probe drug cocktail plus Ze117) vs. Day 1 dosing samples (probe drug cocktail alone). A one-way ANOVA model (with terms for subject and treatment) was applied to analyze the effect of Ze117 on the respective probe drug. Log transformed (base e) parameters were used within the model. The estimated treatment difference between day 8 and day 1 was transformed back to original scale and presented as the ratio between treatments including the corresponding 90% confidence interval. Effect limits were predefined as follows: (1) Mild effect limits (50-200%), extended bioequivalence limits (70-143%), bioequivalence limits (80-125%).

Time frame: PK samples: pre-dose, and 10, 20, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 16, 24, 48 and 72 hours after each cocktail administration (at day 1 and day 8)