Drug Interaction Study
Conditions
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.
Interventions
DRUGZe 117
Subjects will be hospitalized to receive a probe drug cocktail alone and in combination with Ze 117.
Subjects will be hospitalized to receive a probe drug cocktail alone and in combination with Ze 117.
Sponsors
Max Zeller Soehne AG
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
open-label, non-randomized, single-sequence study
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ratio AUC0-t, Day 17 (Probe Drug Cocktail Plus Ze117 [Only at Day 17]) vs. Day 1 (Probe Drug Cocktail Alone) | 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
| Measure | Time frame | Description |
|---|---|---|
| Ratio AUC0-t, Day 8 (Probe Drug Cocktail Plus Ze117 [Daily Throughout pk Sampling Period]) vs. Day 1 (Probe Drug Cocktail Alone) | 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%). |
| Ratio Cmax, Day 17 (Probe Drug Cocktail Plus Ze117 [Only at Day 17]) vs. Day 1 (Probe Drug Cocktail Alone) | 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%). |
| Ratio Cmax, Day 8 (Probe Drug Cocktail Plus Ze117 [Daily Throughout pk Sampling Period]) vs. Day 1 (Probe Drug Cocktail Alone) | 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%). |
Countries
Germany
Contacts
PRINCIPAL_INVESTIGATORMichael Lissy
Neu-Ulm
Participant flow
Recruitment details
Healthy volunteers
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 20 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 20 Participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 20 |
| other Total, other adverse events | 16 / 20 |
| serious Total, serious adverse events | 0 / 20 |
Outcome results
None listed