Trial Outcomes & Findings for Drug Cocktail Interaction Study of St. John's Wort Dry Extract Ze 117 (NCT NCT03482817)
NCT ID: NCT03482817
Last Updated: 2026-06-18
Results Overview
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%).
COMPLETED
PHASE1
20 participants
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)
2026-06-18
Participant Flow
Healthy volunteers
Participant milestones
| Measure |
Healthy Volunteers
20 healthy volunteers receiving in in a single sequence the probe drug cocktail alone (day 1), then two times the probe drug cocktail and the test drug Ze117 (day 8 and day 17)
|
|---|---|
|
Overall Study
STARTED
|
20
|
|
Overall Study
COMPLETED
|
19
|
|
Overall Study
NOT COMPLETED
|
1
|
Reasons for withdrawal
| Measure |
Healthy Volunteers
20 healthy volunteers receiving in in a single sequence the probe drug cocktail alone (day 1), then two times the probe drug cocktail and the test drug Ze117 (day 8 and day 17)
|
|---|---|
|
Overall Study
Adverse Event
|
1
|
Baseline Characteristics
Drug Cocktail Interaction Study of St. John's Wort Dry Extract Ze 117
Baseline characteristics by cohort
| Measure |
Healthy Volunteers
n=20 Participants
20 healthy volunteers receiving in in a single sequence the probe drug cocktail alone (day 1), then two times the probe drug cocktail and the test drug Ze117 (day 8 and day 17)
|
|---|---|
|
Age, Categorical
<=18 years
|
20 Participants
n=20 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
0 Participants
n=20 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=20 Participants
|
|
Sex: Female, Male
Female
|
10 Participants
n=20 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=20 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=20 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=20 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=20 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=20 Participants
|
|
Race (NIH/OMB)
White
|
20 Participants
n=20 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=20 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=20 Participants
|
PRIMARY outcome
Timeframe: 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%).
Outcome measures
| Measure |
Dextromethorphan
n=19 Participants
Dextromethorphan (CYP2D6)
|
Midazolam
n=19 Participants
Midazolam (CYP3A4)
|
Fexofenadine
n=19 Participants
Fexofenadine (P-gp)
|
Caffeine
n=19 Participants
Caffeine (CYP1A2)
|
Bupropion
n=19 Participants
Bupropion (CYP2B6)
|
Flurbiprofen
n=19 Participants
Flurbiprofen (CYP2C9)
|
Omeprazole
n=19 Participants
Omeprazole (CYP2C19)
|
|---|---|---|---|---|---|---|---|
|
Ratio AUC0-t, Day 17 (Probe Drug Cocktail Plus Ze117 [Only at Day 17]) vs. Day 1 (Probe Drug Cocktail Alone)
|
147.99 Percentage
Interval 126.3 to 173.4
|
111.3 Percentage
Interval 100.6 to 123.25
|
101.3 Percentage
Interval 89.0 to 115.0
|
99.1 Percentage
Interval 89.4 to 109.9
|
107.4 Percentage
Interval 93.4 to 123.5
|
103.5 Percentage
Interval 97.0 to 110.5
|
101.04 Percentage
Interval 89.3 to 114.3
|
SECONDARY outcome
Timeframe: 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%).
Outcome measures
| Measure |
Dextromethorphan
n=19 Participants
Dextromethorphan (CYP2D6)
|
Midazolam
n=19 Participants
Midazolam (CYP3A4)
|
Fexofenadine
n=19 Participants
Fexofenadine (P-gp)
|
Caffeine
n=19 Participants
Caffeine (CYP1A2)
|
Bupropion
n=19 Participants
Bupropion (CYP2B6)
|
Flurbiprofen
n=19 Participants
Flurbiprofen (CYP2C9)
|
Omeprazole
n=19 Participants
Omeprazole (CYP2C19)
|
|---|---|---|---|---|---|---|---|
|
Ratio AUC0-t, Day 8 (Probe Drug Cocktail Plus Ze117 [Daily Throughout pk Sampling Period]) vs. Day 1 (Probe Drug Cocktail Alone)
|
162.2 Percentage
Interval 141.0 to 186.6
|
120.5 Percentage
Interval 111.1 to 130.8
|
97.1 Percentage
Interval 87.5 to 107.8
|
105.1 Percentage
Interval 94.3 to 117.2
|
107.0 Percentage
Interval 96.0 to 119.3
|
99.1 Percentage
Interval 93.8 to 104.6
|
118.7 Percentage
Interval 102.6 to 137.2
|
SECONDARY outcome
Timeframe: 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%).
Outcome measures
| Measure |
Dextromethorphan
n=19 Participants
Dextromethorphan (CYP2D6)
|
Midazolam
n=19 Participants
Midazolam (CYP3A4)
|
Fexofenadine
n=19 Participants
Fexofenadine (P-gp)
|
Caffeine
n=19 Participants
Caffeine (CYP1A2)
|
Bupropion
n=19 Participants
Bupropion (CYP2B6)
|
Flurbiprofen
n=19 Participants
Flurbiprofen (CYP2C9)
|
Omeprazole
n=19 Participants
Omeprazole (CYP2C19)
|
|---|---|---|---|---|---|---|---|
|
Ratio Cmax, Day 17 (Probe Drug Cocktail Plus Ze117 [Only at Day 17]) vs. Day 1 (Probe Drug Cocktail Alone)
|
154.6 Percentage
Interval 131.7 to 181.4
|
117.2 Percentage
Interval 103.2 to 133.2
|
116.8 Percentage
Interval 99.4 to 137.1
|
99.1 Percentage
Interval 85.8 to 114.4
|
111.6 Percentage
Interval 88.5 to 140.7
|
111.1 Percentage
Interval 102.1 to 121.0
|
100.6 Percentage
Interval 83.5 to 121.3
|
SECONDARY outcome
Timeframe: 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%).
Outcome measures
| Measure |
Dextromethorphan
n=19 Participants
Dextromethorphan (CYP2D6)
|
Midazolam
n=19 Participants
Midazolam (CYP3A4)
|
Fexofenadine
n=19 Participants
Fexofenadine (P-gp)
|
Caffeine
n=19 Participants
Caffeine (CYP1A2)
|
Bupropion
n=19 Participants
Bupropion (CYP2B6)
|
Flurbiprofen
n=19 Participants
Flurbiprofen (CYP2C9)
|
Omeprazole
n=19 Participants
Omeprazole (CYP2C19)
|
|---|---|---|---|---|---|---|---|
|
Ratio Cmax, Day 8 (Probe Drug Cocktail Plus Ze117 [Daily Throughout pk Sampling Period]) vs. Day 1 (Probe Drug Cocktail Alone)
|
163.3 Percentage
Interval 144.0 to 185.2
|
123.5 Percentage
Interval 108.6 to 140.4
|
102.1 Percentage
Interval 89.6 to 116.5
|
104.3 Percentage
Interval 93.7 to 116.2
|
100.8 Percentage
Interval 84.4 to 120.5
|
109.7 Percentage
Interval 100.7 to 119.5
|
109.7 Percentage
Interval 91.5 to 131.5
|
Adverse Events
One-sequence, Drug Cocktail and Test Product
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
One-sequence, Drug Cocktail and Test Product
n=20 participants at risk
20 healthy volunteers entered the study, one participant dropped out on day5 due to an adverse Event (Tonsillitis)
|
|---|---|
|
General disorders
Fatigue
|
15.0%
3/20 • Number of events 3 • AEs have been measured from screening Day -1 until end of study visit Day 18. In case of ongoing AEs at the end of study or if participants terminated the study prematurely a follow up visit was performed within the next 30 days to control whether AE/SAE has been resolved.
|
|
General disorders
Feeling hot
|
10.0%
2/20 • Number of events 2 • AEs have been measured from screening Day -1 until end of study visit Day 18. In case of ongoing AEs at the end of study or if participants terminated the study prematurely a follow up visit was performed within the next 30 days to control whether AE/SAE has been resolved.
|
|
General disorders
Pyrexia
|
10.0%
2/20 • Number of events 2 • AEs have been measured from screening Day -1 until end of study visit Day 18. In case of ongoing AEs at the end of study or if participants terminated the study prematurely a follow up visit was performed within the next 30 days to control whether AE/SAE has been resolved.
|
|
Gastrointestinal disorders
Abnormal feces
|
5.0%
1/20 • Number of events 1 • AEs have been measured from screening Day -1 until end of study visit Day 18. In case of ongoing AEs at the end of study or if participants terminated the study prematurely a follow up visit was performed within the next 30 days to control whether AE/SAE has been resolved.
|
|
Gastrointestinal disorders
Dry mouth
|
5.0%
1/20 • Number of events 1 • AEs have been measured from screening Day -1 until end of study visit Day 18. In case of ongoing AEs at the end of study or if participants terminated the study prematurely a follow up visit was performed within the next 30 days to control whether AE/SAE has been resolved.
|
|
Gastrointestinal disorders
Gastric hypertonia
|
5.0%
1/20 • Number of events 1 • AEs have been measured from screening Day -1 until end of study visit Day 18. In case of ongoing AEs at the end of study or if participants terminated the study prematurely a follow up visit was performed within the next 30 days to control whether AE/SAE has been resolved.
|
|
Gastrointestinal disorders
Nausea
|
5.0%
1/20 • Number of events 1 • AEs have been measured from screening Day -1 until end of study visit Day 18. In case of ongoing AEs at the end of study or if participants terminated the study prematurely a follow up visit was performed within the next 30 days to control whether AE/SAE has been resolved.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
15.0%
3/20 • Number of events 3 • AEs have been measured from screening Day -1 until end of study visit Day 18. In case of ongoing AEs at the end of study or if participants terminated the study prematurely a follow up visit was performed within the next 30 days to control whether AE/SAE has been resolved.
|
|
Respiratory, thoracic and mediastinal disorders
Epitaxis
|
5.0%
1/20 • Number of events 1 • AEs have been measured from screening Day -1 until end of study visit Day 18. In case of ongoing AEs at the end of study or if participants terminated the study prematurely a follow up visit was performed within the next 30 days to control whether AE/SAE has been resolved.
|
|
Eye disorders
Eye lid edema
|
5.0%
1/20 • Number of events 1 • AEs have been measured from screening Day -1 until end of study visit Day 18. In case of ongoing AEs at the end of study or if participants terminated the study prematurely a follow up visit was performed within the next 30 days to control whether AE/SAE has been resolved.
|
|
Eye disorders
Photophobia
|
5.0%
1/20 • Number of events 1 • AEs have been measured from screening Day -1 until end of study visit Day 18. In case of ongoing AEs at the end of study or if participants terminated the study prematurely a follow up visit was performed within the next 30 days to control whether AE/SAE has been resolved.
|
|
Infections and infestations
Tonsillitis
|
5.0%
1/20 • Number of events 1 • AEs have been measured from screening Day -1 until end of study visit Day 18. In case of ongoing AEs at the end of study or if participants terminated the study prematurely a follow up visit was performed within the next 30 days to control whether AE/SAE has been resolved.
|
|
Respiratory, thoracic and mediastinal disorders
Viral upper respiratory tract infection
|
5.0%
1/20 • Number of events 1 • AEs have been measured from screening Day -1 until end of study visit Day 18. In case of ongoing AEs at the end of study or if participants terminated the study prematurely a follow up visit was performed within the next 30 days to control whether AE/SAE has been resolved.
|
|
Investigations
ALT increased
|
5.0%
1/20 • Number of events 1 • AEs have been measured from screening Day -1 until end of study visit Day 18. In case of ongoing AEs at the end of study or if participants terminated the study prematurely a follow up visit was performed within the next 30 days to control whether AE/SAE has been resolved.
|
|
Investigations
WBC descreased
|
5.0%
1/20 • Number of events 1 • AEs have been measured from screening Day -1 until end of study visit Day 18. In case of ongoing AEs at the end of study or if participants terminated the study prematurely a follow up visit was performed within the next 30 days to control whether AE/SAE has been resolved.
|
|
Psychiatric disorders
Insomnia
|
5.0%
1/20 • Number of events 1 • AEs have been measured from screening Day -1 until end of study visit Day 18. In case of ongoing AEs at the end of study or if participants terminated the study prematurely a follow up visit was performed within the next 30 days to control whether AE/SAE has been resolved.
|
|
Psychiatric disorders
Restlessness
|
5.0%
1/20 • Number of events 1 • AEs have been measured from screening Day -1 until end of study visit Day 18. In case of ongoing AEs at the end of study or if participants terminated the study prematurely a follow up visit was performed within the next 30 days to control whether AE/SAE has been resolved.
|
|
Ear and labyrinth disorders
Ear pain
|
5.0%
1/20 • Number of events 1 • AEs have been measured from screening Day -1 until end of study visit Day 18. In case of ongoing AEs at the end of study or if participants terminated the study prematurely a follow up visit was performed within the next 30 days to control whether AE/SAE has been resolved.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
5.0%
1/20 • Number of events 1 • AEs have been measured from screening Day -1 until end of study visit Day 18. In case of ongoing AEs at the end of study or if participants terminated the study prematurely a follow up visit was performed within the next 30 days to control whether AE/SAE has been resolved.
|
|
Vascular disorders
Hematoma
|
5.0%
1/20 • Number of events 1 • AEs have been measured from screening Day -1 until end of study visit Day 18. In case of ongoing AEs at the end of study or if participants terminated the study prematurely a follow up visit was performed within the next 30 days to control whether AE/SAE has been resolved.
|
|
Nervous system disorders
Headache
|
20.0%
4/20 • Number of events 6 • AEs have been measured from screening Day -1 until end of study visit Day 18. In case of ongoing AEs at the end of study or if participants terminated the study prematurely a follow up visit was performed within the next 30 days to control whether AE/SAE has been resolved.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place