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Completed

NCT Number: NCT03482817

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

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.

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Key information

Conditions

Drug Interaction Study

Age range

18 year–55 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Nuvisan GmbH

Neu-Ulm, Germany

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Ze 117

Drug

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

Other names: St. John's wort dry extract Ze 117

Probe Drug Cocktail

Drug

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

Primary outcomes

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

    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)

    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%).

Secondary outcomes

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

    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)

    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%).

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

    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)

    The "number" as provided in the tables is the ratio (in %) of geometric LS means of Cmax from 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%).

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

    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)

    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%).

Sponsors and collaborators

Lead sponsor

Max Zeller Soehne AG

Industry

Registry information

Official study 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

Important dates

Study start
2018
Primary completion
2018
Study completion
2018
First posted
Mar 29, 2018
Registry last updated
Jun 18, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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