Pilot Pharmacokinetic Study of a Prolonged-release Formulation of St. John's Wort Extract Ze 117

Study Overview
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Brief Summary
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A pilot phase I, randomised, open mono-center, two parallel group clinical trial investigating the pharmacokinetics of a prolonged-release formulation in comparison to an immediate-release formulation of St. John's wort extract Ze 117 in healthy male volunteers under fasting condition.

Official Title
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A Pilot Phase I, Randomised, Open Mono-center, Multiple Dose, Two Parallel Groups Clinical Trial Investigating the Pharmacokinetics of a Prolonged-release Formulation in Comparison to an Immediate-release Formulation of St. John's Wort Extract Ze 117 in Healthy Male Volunteers Under Fasting Condition

Conditions
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Healthy

Intervention / Treatment
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* Drug: St. John's wort prolonged-release tablet 500 mg
* Drug: St. John's wort film coated tablets 250 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Caucasian male volunteers Physically and mentally healthy as judged by means of a medical and standard laboratory examination BMI of between 19 and 29 kg/m2, inclusively Weight not exceeding 90 kg Non-smokers (confirmed by urine cotinine test) Informed cConsent as documented by signature Exclusion Criteria: Known or suspected hypersensitivity to any ingredient of the investigational medicinal product Any clinically significant illnesses or clinically significant surgery within 1 year prior to the administration of the study medication Any surgical or medical condition which might interfere with absorption, distribution, metabolism or excretion of the drug Any clinically significant abnormality or abnormal laboratory test results, as judged by the investigator found during the medical screening Positive test of hepatitis B, hepatitis C or HIV screening (HIV antibody, Hepatitis B (HBsAg), Hepatitis C (HCV) ECG abnormalities (clinical significant) or vital signs abnormalities (systolic blood pressure lower than 90 or over 145 mmHg, diastolic blood pressure lower than 60 or over 95 mmHg, or heart rate less than 45 or over 100bpm) at screening History of asthma or obstructive pulmonary disease (e.g.COPD) Known photohypersensitivity. Presents or history of alcohol dependence within the last year (> 40 g ethanol/d or more than 10 units per weeks (1unit=150 ml of wine or 360 ml of beer or 45 ml alcohol 45%)) History of drug dependence or positive results of drug screen Concomitant participation in another clinical trial within the 4 weeks prior to the planned first drug administration. Donation of blood or blood products within 30 days prior to the planned first drug administration. Treatment with any medication or topical drugs with systemic action used in the past 4 weeks, prior to the planned first drug administration ,or 6 times the half-life of the respective drug, whatever is longer (excluding single use of paracetamol or ibuprofen up to 24 hours prior to the planned first drug administration). Suspected inability, e.g. language problems, or known or suspected non-compliance, e.g. non-willingness to fulfil the dietary restrictions Difficulty to swallow study medication Enrolment of the investigator, his/her family members, employees and other dependent persons Any reason which, in the opinion of the Investigator, would prevent the subject from participating the study

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

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Test<br>St. John's wort prolonged-release tablet 500 mg | Drug: St. John's wort prolonged-release tablet 500 mg<br> <br> * Other names: Prolonged-release formulation;|
| Active Comparator: Reference<br>St. John's wort film coated tablets 250 mg (Remotiv N) | Drug: St. John's wort film coated tablets 250 mg<br> <br> * Other names: Immediate-release formulation;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Half Value Duration (HVD) of surrogate markers of the total extract Ze 117 |  | 3 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak-trough fluctuation (PTF) of surrogate markers of the total extract Ze 117 |  | 3 days | 
| Tmax of surrogate markers of the total extract Ze 117 |  | 3 days | 
| AUCss of surrogate markers of the total extract Ze 117 |  | 3 days | 
| Cmax of surrogate markers of the total extract Ze 117 |  | 3 days | 
| Cmin of surrogate markers of the total extract Ze 117 |  | 3 days | 
| lag time of surrogate markers of the total extract Ze 117 |  | 3 days | 
| Mean Residence Time (MRT) of surrogate markers of the total extract Ze 117 |  | 3 days | 
| T1/2 of surrogate markers of the total extract Ze 117 |  | 3 days | 
| Half value Duration (HVD) of hyperforin |  | 3 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pharmacokinetics